Selected References Documenting the Scientific
Advances in “Adult” Stem Cell Research –
Current Treatments Update
(Post-Natal or Tissue Stem Cells, which are not derived from embryos)

The majority of the sources cited in this reference list are articles published in peer-reviewed
scientific and medical journals. Some are reviews of scientific research. This document is organized by subject area, so some references may appear more than once.

Treatments with Adult Stem Cells - David A. Prentice

CURRENT CLINICAL APPLICATIONS OF ADULT STEM CELLS

CANCER TREATMENTS

BRAIN TUMORS
Combination of high-dose chemotherapy with stem cell transplant from the patients themselves
shows good response in treatment of brain tumors.
Reference:
Dunkel, IJ; “High-dose chemotherapy with autologous stem cell rescue for malignant brain tumors”; Cancer Invest. 18, 492-493; 2000.

“Patients with recurrent medulloblastoma had a significant improvement in long-term survival
(median: 34 months) as compared with historical reports; two patients with glioblastoma
survive beyond four years without progression.”
Reference:
Abrey, LE et al.; “High dose chemotherapy with autologous stem cell rescue in adults with malignant primary brain tumors”; J. Neurooncol. 44, 147-153; Sept. 1999

“Review of HDCT and stem cell transplant for children with brain tumors. Studies demonstrating
durable disease- free survival for a proportion of patients with recurrent malignant gliomas and
medulloblastomas/PNET, as well as encouraging data in some of those patients with newly
diagnosed brain tumors.”
Reference:
Finlay, JL; “The role of high-dose chemotherapy and stem cell rescue in the treatment of malignant brain tumors: a reappraisal”; Pediatr. Transplant 3 Suppl. 1, 87-95; 1999

RETINOBLASTOMA
A localized retinoblastoma of the left eye in a 7-year-old girl, was treated by enucleation. She
received no additional therapy. Four months later, metastases of retinoblastoma in the lymph
nodes, bone and bone marrow were diagnosed. Relapse chemotherapy consisting of three
courses of vincristine, cyclophosphamide, etoposide and carboplatin led to a second complete
remission. Subsequent high-dose chemotherapy with thiotepa, etoposide and carboplatin and
autologous stem cell transplantation with CD34-selected stem cells were successful, with no
adverse effects. No radiotherapy was given and the girl remains in continuous second
remission with a follow-up of more than 4 years.
Reference:
Hertzberg H et al.; “Recurrent disseminated retinoblastoma in a 7-year-old girl treated successfully by high-dose chemotherapy and CD34-selected autologous peripheral blood stem cell
transplantation”; Bone Marrow Transplant 27(6), 653-655; March 2001

Patients with metastatic retinoblastoma have a poor prognosis with conventional treatments. This study used intensive conventio nal chemotherapy, high-dose chemotherapy, with autologous
stem cell rescue, and radiation therapy. The treatment strategy was effective for all four patients with metastatic retinoblatoma that does not involve the central nervous system,
surviving event free from 46-80 months after diagnosis.
Reference:
Dunkel IJ et al.; “Successful treatment of metastatic retinoblastoma”; Cancer 89, 2117-2121; Nov. 15, 2000

OVARIAN CANCER
Report studying whether patients benefit more from autologous stem cell transplantation. “Some
patients with ovarian cancer seem to have good outcomes after autotransplantation”.
Reference:
Stiff PJ et al.; “High-dose chemotherapy and autologous stem-cell transplantation for ovarian cancer: An autologous blood and marrow transplant regis try report”; Ann. Intern. Med. 133, 504-515; Oct. 3, 2000

“Developing data suggest that this approach in both of these settings merit further evaluation for the treatment of epithelial ovarian carcinoma.” Used autologous, purified peripheral blood stem cells
Reference:
Schilder, RJ and Shea, TC; “Multiple cycles of high-dose chemotherapy for ovarian cancer”; Semin. Oncol. 25, 349-355; June 1998

SOLID TUMORS
Use of patients’ own bone marrow or blood stem cells leads to long-term recovery from various types of solid tumors.
Reference:
Nieboer P et al.; “Long-term haematological recovery following high-dose chemotherapy with
autologous bone marrow transplantation or peripheral stem cell transplantation in patients with solid tumours”; Bone Marrow Transplant 27, 959-966; May 2001

Merkel cell carcinoma is a rare cutaneous tumor with neuroendocrine differentiation; there is no
standard protocol for treatment of the metastatic disease. This study used high-dose
chemotherapy and autologous peripheral blood stem cell transplantation to achieve complete
remission that lasted for 6 months.
Reference:
Waldmann V et al.; “Transient complete remission of metastasized merkel cell carcinoma by highdose polychemotherapy and autologous peripheral blood stem cell transpla ntation”; Br. J.
Dermatol. 143, 837-839; Oct. 2000

Patients with metastatic or locally advanced, unresectable soft tissue sarcoma are seldom curable, with 5- year survival rates of less than 10%. Used high-dose chemotherapy with autologous hematopoietic stem cell transplant; “a high survival rate was observed in HDCT-treated patients who were in complete remission after conventional chemotherapy.”
Reference:
Blay JY et al.; “High-dose chemotherapy with autologous hematopoietic stem-cell transplantation for advanced soft tissue sarcoma in adults”; J. Clin. Oncol. 18, 3643-3650; Nov. 1, 2000

“The prognosis of metastatic malignant mesenchymal tumors (MMT) remains poor.” Used high-dose chemotherapy with bone marrow or peripheral blood stem cell transplant. “A response
exceeding 50% was observed in 6/18 patients (response rate 33%).”
Reference:
Lafay-Cousin L et al.; “High-dose thiotepa and hematopoietic stem cell transplantation in pediatricmalignant mesenchymal tumors: a phase II study”; Bone Marrow Transplant 26, 627-632;
Sept. 2000

High-dose chemotherapy followed by autologous haematopoietic rescue is widely used in the
treatment of patients with paediatric malignancies. It is now well established as a major
component for the treatment of children with metastatic neuroblastoma over the age of one at
diagnosis. Its place for other tumours, such as metastatic Ewing and rhabdomyosarcoma,
needs to be better established.”
Reference:
Michon, J and Schleiermacher, G. “Autologous haematopoietic stem cell transplantation for
paediatric solid tumors”, Baillieres Best Practice Research in Clinical Haematology 12, 247-
259, March-June 1999.

Used for malignant solid tumors. Overall response rate 96%, complete clinical response rate 67%.
Treatment described as safe, feasible, and active.
Reference:
Schilder, RJ et al.; “Phase I trial of multiple cycles of high-dose chemotherapy supported by
autologous peripheral-blood stem cells”; J. Clin. Oncol. 17, 2198-2207; July 1999

TESTICULAR CANCER
“Thirty-seven (57%) of the 65 patients are continuously disease- free. Three additional patients are disease- free with subsequent surgery. High-dose chemotherapy was associated with
significant morbidity but no treatment-related mortality. High-dose chemotherapy as initial
salvage chemotherapy achieved impressive long-term survival with acceptable toxicity in
patients with relapsed testicular cancer.”
Reference:
Bhatia S et al.; “High-dose chemotherapy as initial salvage chemotherapy in patients with relapsed testicular cancer”; J. Clin. Oncol. 18, 3346-3351; Oct. 19, 2000

“High-dose chemotherapy with the transplantation of peripheral blood stem cells (PBSC) has been
performed for the treatment of advanced testicular cancer patients.” “After mobilization of
peripheral blood stem cells with G-CSF alone, sufficient amounts of MNC were obtained from testicular cancer patients who had undergone chemotherapy several times.”
Reference:
Hanazawa, K et al.; “Collection of peripheral blood stem cells with granulocyte-colony-stimulating
factor alone in testicular cancer patients”; Int. J. Urol. 7, 77-82; March 2000.

MULTIPLE MYELOMA, LEUKEMIAS
Umbilical Cord Blood Effective At Treating Adult Blood Disorders
A new report shows that umbilical cord blood can provide effective treatment of various blood
disorders in adults. It had previously been assumed that there were too few stem cells in cord blood to treat adults, and only children were treated. The results of this study show that cord blood stem cells can proliferate extensively and provide sufficient numbers of cells for adult treatments.
Reference:
Laughlin MJ et al.; “Hematopoietic engraftment and survival in adult recipients of umbilical-cord
blood from unrelated donors”, New England Journal of Medicine 344, 1815-1822; June 14, 2001

Bone marrow/peripheral blood stem cell treatments can be used to treat older patients
Reference:
Tabata M et al.; “Peripheral blood stem cell transplantation in patients over 65 years old with
malignant lymphoma--possibility of early completion of chemotherapy and improvement of
performance status”; Intern Med 40, 471-474; June 2001

Successfully treated lymphoma using patient’s own stem cells.
Reference:
Koizumi M et al.; “Successful treatment of intravascular malignant lymphomatosis with high-dose
chemotherapy and autologous peripheral blood stem cell transplantation”; Bone Marrow Transplant 27, 1101-1103; May 2001

This retrospective study included 21 children with acute lymphoblastic leukaemia, 15 with acute
myelogenous leukaemia and one each with chronic myelogenous leukaemia, refractory anaemia with myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukaemia (JMML). These data confirm that HLA-mismatched, unrelated Cord Blood Transplant is a feasible procedure to cure a significant proportion of children with leukaemia, especially if conducted in a favourable phase of the disease.
Reference:
Ohnuma K et al.; “Cord blood transplantation from HLA- mismatched unrelated donors as a treatment for children with haematological malignancies”; Br J Haematol 112(4), 981-987; March 2001

Angioimmunoblastic lymphadenopathy with dysproteinemia (or dysgammaglobulinemia) (AILD) is
a lymphoproliferative disorder with abnormalities characteristic of malignant T-cell lymphoma
(angioimmunoblastic T-cell lymphoma -- AITL). We report the clinical course of a 58-year-old male patient with unusually aggressive AILD, At relapse, treatment with high-dose chemotherapy
followed by autologous peripheral stem cell transplantation (APSCT) with CD34 selected cells was
shown to be successful. The patient is alive and disease-free 3 years after diagnosis and 32 months after APSCT. Considering the poor prognosis of the majority of patients with AILD, intensive treatment followed by APSCT, may be a subject for further studies.
Reference:
Lindahl J et al.; “High-dose chemotherapy and APSCT as a potential cure for relapsing hemolysing
AILD”; Leuk Res 25(3), 267-270; March 2001

Patients given high-dose chemotherapy followed by allogeneic stem cell transplants. Peripheral
blood stem cells rather than bone marrow results in higher rates of overall and disease- free survival, and restores blood counts faster. Patients in whom the benefit of peripheral-blood cells was most apparent were those with advanced hematologic cancer. Other studies have also shown that the use of peripheral-blood cells is associated with fewer days of hospitalization and lower overall costs.
Reference:
Bensinger WI et al.; “Transplantation of bone marrow as compared with peripheral-blood cells from HLA- identical relatives in patients with hematologic cancers”; New England Journal of
Medicine 344, 175-181; Jan. 18, 2001

**Review of new procedures involving stem cell transplantation. The authors note that “Stem cell
transplantation has been successfully used to treat a wide variety of hematologic malignancies. New and exciting strategies being developed for use in conjunction with transplant will be useful in overcoming tumor resistance.”
Reference:
Margolis J et al.; “New approaches to treating malignances with stem cell transplantation”; Semin. Oncol. 27, 524-530; Oct. 2000

**Study notes that “autologous stem cell transplantation is a potential therapeutic approach in
patients with acute myelocytic leukemia over 60 years of age.”
Reference:
Gorin NC et al.; “Feasibility and recent improvement of autologous stem cell transplantation for acute myelocytic leukaemia in patients over 60 years of age: importance of the source of stem
cells”; Br. J. Haematol. 110, 887-893; Sept. 2000

“Infants with acute leukemia have a poor prognosis when treated with conventional chemotherapy.” 5-year overall survival 64%. “SCT is a valid option in the treatment of infant acute leukemia, and it may overcome the high risk of relapse with conventional chemotherapy showing very reduced toxicity.”
Reference:
Marco F et al.; “High Survival Rate in Infant Acute Leukemia Treated With Early High-Dose
Chemotherapy and Stem-Cell Support”; J Clin Oncol 18, 3256-3261; Sept. 15, 2000

“Actuarial survival and disease-free survival at 34 months are 56% and 50% respectively, with 95% confidence interval (25-78%).These results suggest that nonmyeloablative conditioning
significantly reduces transplant-related toxicity, thus making a second transplant feasible.”
Reference:
Nagler A et al.; “Second allogeneic stem cell transplantation using nonmyeloablative conditioning for patients who relapsed or developed secondary malignancies following autologous
transplantation”; Exp. Hematol. 28, 1096-1104, Sept. 1, 2000

Review of autologous stem cell treatment strategies. “Controlled clinical trials have demonstrated a long-term disease- free survival of 40%-50% for patients treated with at least two courses of HIDAC. Other studies have demonstrated that postremission autologous bone marrow
transplantation results in a disease-free survival equal to or better than conventional chemotherapy. However, autotransplantation with mobilized peripheral blood stem cells (PBSC) would now be preferred instead of autologous bone marrow, due to the shorter hematopoietic reconstitution period.”
Reference:
Bruserud O et al.; “New strategies in the treatment of acute myelogenous leukemia: mobilization and transplantation of autologous peripheral blood stem cells in adult patients”; Stem Cells 18,
343-351; 2000

Study to evaluate high-dose melphalan followed by autologous stem-cell transplantation in patients with refractory multiple myeloma. High-dose therapy with melphalan 200 mg/m(2) is
feasible with high response rates (58% overall) and an OS of 19 months in patients with
refractory multiple myeloma.”
Reference:
Vesole, DH et al.; “High-Dose Melphalan With Autotransplantation for Refractory Multiple
Myeloma: Results of a Southwest Oncology Group Phase II Trial”; J Clin Oncol 17, 2173-
2179; July 1999.

BREAST CANCER
The “data suggest that high-dose chemotherapy with hematopoietic stem cell rescue is safe and can be beneficial to patients with high-risk primary breast cancer and for those with metastatic
breast cancer achieving complete response/no evidence of disease.”
Reference:
Damon LE et al.; “High-dose chemotherapy and hematopoietic stem cell rescue for breast cancer:
experience in California”; Biol. Blood Marrow Transplant 6, 496-505; 2000

Stem cells in circulating blood can be isolated, expanded in number in culture, and provide better
clinical results.
Reference:
Paquette, RL et al., “Ex vivo expanded unselected peripheral blood: progenitor cells reduce
posttransplantation neutropenia, thrombocytopenia, and anemia in patients with breast
cancer”, Blood 96, 2385-2390; October 2000.

“The collection of small aliquots of bone marrow (BM), followed by ex vivo expansion for
autologous transplantation may be less morbid, and more cost-effective, than typical BM or
blood stem cell harvesting. Passive elimination of contaminating tumor cells during expansion
could reduce reinoculation risks.” “It is feasible to perform autotransplants solely with BM
cells grown ex vivo in perfusion bioreactors from a small aliquot.” “This procedure could
reduce the risk of tumor cell reinoculation with autotransplants and may be valuable in
settings in which small stem cell doses are available, eg, cord blood transplants.”
Reference:
Stiff P et al.; “Autologous transplantation of ex vivo expanded bone marrow cells grown from small aliquots after high-dose chemotherapy for breast cancer”; Blood 95, 2169-2174; March 15,
2000

“This report is the first describing infusion of autologous MSCs with therapeutic intent. We found
that autologous MSC infusion at the time of PBPC transplantation is feasible and safe. The
observed rapid hematopoietic recovery suggests that MSC infusion after myeloablative therapy may have a positive impact on hematopoiesis and should be tested in randomized trials.”
Reference:
Koc, ON et al.; “Rapid Hematopoietic Recovery After Coinfusion of Autologous-Blood Stem Cells
and Culture-Expanded Marrow Mesenchymal Stem Cells in Advanced Breast Cancer Patients
Receiving High-Dose Chemotherapy”; J Clin Oncol 18, 307-316; January 2000

NEUROBLASTOMA
“According to initial reports, stage 4 neuroblastoma patients with amplification of the MYCN protooncogene developed progressive disease within 8 months. The prognosis for such patients,
however, should now be reevaluated in light of recent results achieved with up-to-date
combination chemotherapy. Not all patients with advanced neuroblastoma who have more
than 10 copies of MYCN will die. The requisites for survival in such patients seem to be
intensive induction chemotherapy, effective surgery, irradiation, and the use of SCT” (stem
cell transplant).
Reference:
Kawa, K et al.; “Long-Term Survivors of Advanced Neuroblastoma With MYCN Amplification: A
Report of 19 Patients Surviving Disease-Free for More Than 66 Months”; J Clin Oncol
17:3216-3220; October 1999

NON-HODGKIN’S LYMPHOMA
Tabata M et al.; “Peripheral blood stem cell transplantation in patients over 65 years old with
malignant lymphoma--possibility of early completion of chemotherapy and improvement of
performance status”; Intern Med 40, 471-474; June 2001

“To determine differences in prognosis between primary progressive Hodgkin's disease (HD) and
aggressive non-Hodgkin's lymphoma (NHL), we retrospectively analyzed patients with progressive lymphoma who were treated with different salvage chemotherapy regimens including high-dose chemotherapy (HDCT) followed by autologous stem-cell support (ASCT). There are striking differences in the prognosis of patients with progressive HD and aggressive NHL. The prognosis of progressive NHL patients is dismal. Most patients have rapidly progressive disease after salvage treatment and are, therefore, excluded from HDCT programs. In contrast, progressive HD patients can achieve long-term survival after HDCT.”
Reference:
Josting, A; “Treatment of Primary Progressive Hodgkin’s and Aggressive Non-Hodgkin’s
Lymphoma: Is There a Chance for Cure?”; J Clin Oncol 18, 332-339; 2000

“Patient achieved complete remission and has survived in continuous complete remission for more than 72 months to date. Marrow-ablative chemotherapy facilitated by PBSCT is thought to be useful as part of the primary therapy for patients with NHL who have poorer prognoses.”
Reference:
Kirita T et al.; “Primary non-Hodgkin’s lymphoma of the mandible treated with radiotherapy,
chemotherapy, and autologous peripheral blood stem cell transplantation”; Oral Surg Oral
Med Oral Pathol Oral Radiol Endod. 90, 450-455; Oct. 2000

“These results suggest first that ex vivo expansion of hematopoietic stem cells in patients with non-Hodgkin's lymphoma is feasible without incurring the parallel risk of amplifying tumor cells;
second, that Flt3-L did not stimulate the growth of tumor cells while it clearly favored the
growth of normal progenitors.”
Reference:
Yao M et al.; “Ex vivo expansion of CD34-positive peripheral blood progenitor cells from patients
with non-Hodgkin’s lymphoma: no evidence of concomitant expansion of contaminating
bcl2/JH-positive lymphoma cells”; Bone Marrow Transplant 26, 497-503; Sept. 2000

“Nonmyeloablative allogeneic stem-cell transplantation can induce sustained regression of metastatic renal-cell carcinoma in patients who have had no response to conventional immunotherapy.”
Reference:
Childs R et al., “Regression of Metastatic Renal-Cell Carcinoma after Nonmyeloablative Allogeneic
Peripheral-Blood Stem-Cell Transplantation”, New England Journal of Medicine 343, 750-
758; Sept. 14, 2000

“The complete regression of metastatic disease, which has now been maintained for more than 1 year, is compatible with a graft-versus-tumor effect.”
Reference:
Childs, RW; “Successful Treatment of Metastatic Renal Cell Carcinoma With a Nonmyeloablative
Allogeneic Peripheral-Blood Progenitor-Cell Transplant: Evidence for a Graft-Versus-Tumor
Effect:; J Clin Oncol 17, 2044-2049; July 1999

AUTOIMMUNE DISEASES
–multiple sclerosis, systemic lupus erythematosus, juvenile rheumatoid
arthritis, rheumatoid arthritis

Adult Stem Cells Treat Potentially Fatal Skin Disorder
A man with scleromyxedema, a rare and potentially fatal skin disease, is reported free of symptoms after receiving a transplant of adult stem cells taken from his own bone marrow. Like scleroderma, scleromyxedema causes the skin to thicken and become hard. Prior to the adult stem cell treatment, the patient could not completely close his eyes, and had lost the ability to eat. Three months after treatment the patient could once again close his eyes and open his mouth to eat. The results are reported in the August issue of Archives of Dermatology.
References:
A.M. Feasel et al., "Complete remission of scleromyxedema following autologous stem cell
transplantation," Archives of Dermatology 137, 1071-1072; Aug. 2001."Stem Cell Transplant Treats Rare Skin Disorder," Reuters Health, August 17, 2001

Patients’ own stem cells to treat severe multiple sclerosis
Use of combined therapy with using a patient’s own stem cells for treatment of severe cases of
multiple sclerosis. Treatment decreased tissue damage in the patients, and had the capacity to
completely suppress further tissue damage, an effect that is sustained with time.
Reference:
Mancardi GL et al.; “Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced
MRI activity in MS”; Neurology 57, 62-68; July 10, 2001

Adult Stem Cells Show Success in Treating Another Autoimmune Disease—Crohn’s Disease
Physicians at Chicago's Northwestern Memorial Hospital report initial success in using adult stem
cells to treat two patients with Crohn's disease, a potentially disabling inflammatory bowel disease. One patient was said to be doing "phenomenally well" 2 ½ months after undergoing the procedure using the adult stem cells, which were extracted from her blood, leading doctors to try it on a second patient. Results in both patients were very encouraging, according to Dr. Richard Burt, who performed the procedures. Burt noted that results of similar procedures on multiple sclerosis patients have also shown progress, and that adult stem cell therapy on patients with lupus had repaired damage to their organs. According to Burt: " 'If you're able to use your own stem cells,' the embryonic stem cell issue is 'not just ethically moot, it's practically moot.' "
Reference:
"Adult Stem Cells Hold Hope for Autoimmune Patients," Reuters Health, Aug. 13, 2001.

High-dose chemotherapy followed by autologous HSCT is feasible and safe, and can result in longterm improvement of disease activity in patients whose condition previously did not respond to conventional antirheumatic drugs or TNF blocking agents. The persistence of active disease in some patients may reflect the heterogeneity of the underlying disease process.
Reference:
Verburg RJ et al.; “High-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with rheumatoid arthritis: results of an open study to assess feasibility, safety, and efficacy”; Arthritis Rheum 44(4), 754-760; April 2001

Reference:
Wulffraat NM et al.; “Prolonged remission without treatment after autologous stem cell
transplantation for refractory childhood systemic lupus erythematosus”; Arthritis Rheum
44(3), 728-731; March 2001

“Autoimmune diseases that are resistant to conventional treatment cause severe morbidity and even mortality. In the present study we demonstrate that complete remissions can be achieved in
refractory polychondritis and systemic lupus erythematosus (SLE), even at advanced stage,
with the use of autologous stem-cell transplantation (SCT). Remissions persisted after
reconstitution of the immune system. In the treatment of advanced systemic sclerosis (SSc),
stable disease may be achieved with autologous SCT.”
Reference:
Rosen O et al.; “Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells”; Arthritis res. 2, 327-336; 2000

Nineteen patients (14 female, 5 male) with severe autoimmune diseases were treated. Nine had a rheumatologic disorder (5 juvenile chronic arthritis, 1 rheumatoid arthritis, 1 systemic
vasculitis, 1 Sjogren's syndrome, 1 Behct's disease), 4 a neurologic disorder (3 multiple
sclerosis, 1 myasthenia), 3 a haematologic disease (2 pure red cell aplasia, 1 autoimmune
thrombocytopenia), 2 had a gastrointestinal disease (1 Crohn's disease, 1 autoimmune
enteropathy) and 1 had a multiple autoimmune disorder. There was no regimen-related
toxicity and no opportunistic infections occurred. Ninety percent of the patients improved
and/or had a complete remission after the procedure. Fifty percent of the subjects went into
complete or partial remission after a median follow-up of 15 months. A non- myeloablative
conditioning regimen was able to induce persistent remission in some patients with severe
autoimmune diseases. There was no mortality or morbidity related to the procedure. The
extent of remission remains to be established.
Reference:
Rabusin M et al.; “Immunoablatio n followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000

Study that supports the concept that patients with autoimmune cytopenias with severe resistant
disease might be appropriate candidates for autologous stem cell transplantation.
Reference:
Papadaki HA et al.; “Assessment of bone marrow stem cell reserve and function and stromal cell
function in patients with autoimmune cytopenias”; Blood 96, 3272-3275; Nov. 1, 2000

Patients (including several children) with severe lupus were treated with their own bone marrow stem cells, and had relief of symptoms, with little or no need for medication after treatment.
References:
Traynor AE et al.; “Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study”; Lancet 356, 701-707; August 26, 2000

Numerous studies showing efficacy of adult stem cell transplants in the successful treatment of
autoimmune diseases.
References:
Burt, RK and Traynor, AE; “Hematopoietic Stem Cell Transplantation: A New Therapy for
Autoimmune Disease”; Stem Cells17, 366-372; 1999

Overview—juvenile rheumatoid arthritis; multiple sclerosis; rheumatoid arthritis; systemic
lupus erythematosus.
Burt RK et al.; “Hematopoietic stem cell transplantation of multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus”; Cancer Treat. Res. 101, 157-184; 1999
Traynor A and Burt RK; “Haematopoietic stem cell transplantation for active systemic lupus
erythematosus”; Rheumatology 38, 767-772; August 1999
Martini A et al.; “Marked and sustained improvement 2 years after autologous stem cell transplant in a girl with system sclerosis”; Rheumatology 38, 773; August 1999
Hawkey CJ et al.; “Stem cell transplantation for inflammatory bowel disease: practical and ethical
issues”; Gut 46, 869-872; June 2000
Burt, RK et al., “Autologous hematopoietic stem cell transplantation in refractory rheumatoid
arthritis: sustained response in two of four patients”, Arthritis & Rheumatology 42, 2281-
2285, November 1999.
Burt, R.K. et al., “Gene-marked autologous hematopoietic stem cell transplantation of autoimmune disease”, Journal of Clinical Immunology 20, 1-9; January 2000.

STROKE

Follow- up study from previous transplant shows improved local cellular function or engraftment
of implanted adult stem cell line in some stroke patients.
Reference:
Meltzer CC et al.; “Serial [18F]Fluorodeoxyglucose Positron Emission Tomography after
Human Neuronal Implantation for Stroke”; Neurosurgery 49, 586-592; 2001.

A cultured stem cell line (originally derived from an adult tumor; a “teratocarcinoma”,
sometimes called an “embryonal carcinoma” because it mimics some of the characteristics of
embryonic cells.) The cultured and adapted cell line was used in successful treatment of several
stroke patients.
Reference:
Kondziolka D et al.; “Transplantation of cultured human neuronal cells for patients with stroke”;
Neurology 55, 565-569; August 2000

IMMUNODEFICIENCIES

Banked unrelated umbilical cord blood was used to reconstitute the immune system in 2 brothers
with X-linked lymphoproliferative syndrome and 1 boy with X-linked hyperimmunoglobulin-M
syndrome. Two years after transplantation, all 3 patients have normal immune systems. These
reports support the wider use of banked partially matched cord blood for transplantation in
primary immunodeficiencies.
Reference:
Ziegner UH et al.; “Unrelated umbilical cord stem cell transplantation for X- linked
immunodeficiencies”; J Pediatr 138(4), 570-573; April 2001

Eight children with severe immunodeficiencies treated by adult bone marrow stem cell
transplants. Six of 8 showed relatively normal immune systems after 1 year.
Reference:
Amrolia, P. et al., “Nonmyeloablative stem cell transplantation for congenital
immunodeficiencies”, Blood 96, 1239-1246, Aug. 15, 2000.

ANEMIAS

Successful treatment of sickle cell anemia using umbilical cord blood stem cells
Used sibling cord blood stem cells.
Reference:
Gore L. et al.; “Successful cord blood transplantation for sickle cell anemia from a sibling who is
human leukocyte antigen- identical: implications for comprehensive care”, J Pediatr Hematol
Oncol 22(5):437-440; Sep-Oct 2000

Inherited anemia treated using donor bone marrow stem cell transplant.
Reference:
Ayas M et al.; “Congenital sideroblastic anaemia successfully treated using allogeneic stem cell
transplantation”; Br J Haematol 113, 938-939; June 2001

Anagnostopoulos A et al.; “High-dose chemotherapy followed by stem cell transplantation in
patients with resistant Waldenstrom's macroglobulinemia”; Bone Marrow Transplant 27, 1027-
1029; May 2001

Allogeneic peripheral blood stem cell transplantation (PBSCT) is rarely applied for the treatment
of severe aplastic anemia (SAA) because of questionable durability of engraftment and
increased risk of graft versus host disease (GVHD). We performed allogeneic PBSCT in
3 SAA patients from their human leukocyte antigen (HLA)- identical siblings. In 2 cases,
no graft failure has been observed, and a successful and complete hematological recovery
was achieved and maintained for 28 and 25 months, respectively. In conclusion, PBSCT
provides a quick and complete hematological recovery in SAA patients.
Reference:
Gurman G et al.; “Allogeneic peripheral blood stem cell transplantation for severe aplastic
anemia”; Ther Apher 5(1), 54-57; Feb. 2001

Results suggest that treatment can reverse progression of vasculopathy. Bone marrow
transplantation may enable stenoses to heal and can substantially reduce cranial blood
velocity, suggesting that allogeneic bone marrow transplantation may prevent infarction
or brain damage.
Reference:
Steen RG et al.; “Improved cerebrovascular patency following therapy in patients with sickle cell
disease: initial results in 4 patients who received HLA- identical hematopoietic stem cell
allografts”; Ann Neurol 49(2), 222-229; Feb. 2001

Able to treat severe anemias using transplants of adult bone marrow stem cells.
References
Gonzalez MI et al.; “Allogeneic peripheral stem cell transplantation in a case of hereditary
sideroblastic anaemia”; British Journal of Haematology 109, 658-660; 2000
Kook H et al.; “Rubella-associated aplastic anemia treated by syngeneic stem cell
transplantations”; Am. J. Hematol. 64, 303-305; August 2000

Possibility of using adult stem cell transplantation as cure for sickle cell anemia.
Reference:
Wethers DL; “Sickle cell disease in childhood: Part II. Diagnosis and treatment of major
complications and recent advances in treatment”; Am. Fam. Physician 62, 1309-1314; Sept. 15,
2000

Successful treatment of a congenital thrombocytopenia using allogeneic peripheral blood stem
cell transplantation.
Reference:
Yesilipek et al.; “Peripheral stem cell transplantation in a child with amegakaryocytic
thrombocytopenia”; Bone Marrow Transplant 26, 571-572; Sept. 2000

Chronic Viral Infection With Complications

Fujii N et al.; “Allogeneic peripheral blood stem cell transplantation for the treatment of chronic
active epstein-barr virus infection”; Bone Marrow Transplant 26, 805-808; Oct. 2000
Okamura T et al.; “Blood stem-cell transplantation for chronic active Epstein- Barr virus with
lymphoproliferation”; Lancet 356, 223-224; July 2000

Cartilage and Bone Diseases

Biopsies removed from 57 patients considered for cartilage transplantation were grown. Explant
cultures allowed cell number expansion. Fifty- four out of 57 biopsies grew cells. Fanning
out of the cells began after 5-15 days in culture. Two passages later, cell numbers in the
10(7) range were achieved. Explants of articular chondrocytes cultured in vitro consistently yield monolayer cultures. The cells appear to revert to dedifferentiated chondrocytes, expressing a mesenchymal stem cell protein profile. Simultaneously, these cells regained their capacity to proliferate.
Reference:
Robinson D et al.; “Characteristics of cartilage biopsies used for autologous chondrocytes
transplantation”; Cell Transplant 10(2), 203-208; 2001 Mar-Apr

Horwitz, EM et al.; “Transplantability and therapeutic effects of bone marrow-derived
mesenchymal cells in children with osteogenesis imperfecta”; Nat. Med. 5, 309-313;
March 1999.

CORNEAL SCARRING

Confluent sheets of cultured corneal epithelial cells, suitable for grafting, can be produced from
limbal tissue taken from eye bank organ-cultured corneas, although it takes longer, on average,
to reach confluence (17–21 days) than an equivalent sample from a fresh eye (9–12 days).
Reference:
James SE et al.; “The Potential for Eye Bank Limbal Rings to Generate Cultured Corneal
Epithelial Allografts”; Cornea 20, 488-494; July 2001

Fifteen of 16 eyes (93.7%) achieved epithelialization with a mean time to epithelial healing of 15.2 days. The only eye that failed to heal was subsequently diagnosed with total limbal stem cell deficiency. Visual acuity improved in five of nine (44%) sighted eyes. No patient experienced any major surgical or medical complication after the procedure. Amniotic membrane transplantation represents a safe and effective method to restore a stable corneal epithelium in eyes after primary surgical removal of band keratopathy arising from ocular causes.
Reference:
Anderson DF et al.; “Amniotic Membrane Transplantation After the Primary Surgical
Management of Band Keratopathy”; Cornea 20(4), 354-361; May 2001

Amniotic membrane transplantation appears to be a safe and effective method of restoring a
stable corneal epithelium for cases of partial limbal stem cell deficiency and can be considered as
an alternative to limbal autograft or allograft. 17 eyes of 15 patients; All eyes exhibited a stable,
intact corneal epithelial surface after a mean follow up period of 25.8 months with no eyes
developing recurrent erosion or persistent epithelial defect. The mean time to re-epithelialisation
was 22.8 days. Overall improvement in visual acuity was observed in 92.9% of 14 eyes with
visual potential.
Reference:
Anderson DF et al.; “Amniotic membrane transplantation for partial limbal stem cell
deficiency”; Br J Ophthalmol 85(5), 567-575; May 2001

An objective long term benefit from the procedure (improved Snellen acuity, reduced frequency
of epithelial defects, reduced vascularisation, and scarring) was recorded for four out of five
patients. Some subjective benefit was also reported. However, in no instances were donor cells
recovered from the ocular surface at 3-5 years post- graft. Initial experiments to examine
sensitivity indicated that any surviving donor cells must have constituted less than 2.5% of cells
sampled. Limbal stem cell allotransplantation can provide long term benefits, as measured by
objective criteria. However, such benefits do not necessarily correlate with survival of
measurable numbers of donor cells on the ocular surface.
Reference:
Henderson TR et al.; “The long term outcome of limbal allografts: the search for surviving
cells”; Br J Ophthalmol 85(5), 604-609; May 2001

Adult stem cells from relatives used to restore vision
Nine living related donors, 8 recipients (10 eyes, various conditions). Restoration of corneal
epithelium, opacification reduced, visual improvement; 2 initial failures.
Reference:
Daya SM, Ilari FA; “Living related conjuctival limbal allograft for the treatment of stem cell
deficiency”; Opthalmology 180, 126-133; January 2001

Adult Stem Cells Used to Grow New Corneas
Researchers in the United States and Taiwan have used corneal adult stem cells to grow new
corneas for patients with previously untreatable eye damage. Adult stem cells were taken from
the patients themselves in 16 cases, or a family member for 4 other patients. The cells were then
grown in culture before transplantation onto the damaged eyes. Sixteen of the 20 patients had
improved vision. Dr. Ivan Schwab, professor of ophthalmology at the University of California at
Davis Medical School, leader of the U.S. team, said “We think this is the beginning of a very
exciting change in terms of how we manage surface disease of many kinds, not just in the eye.”
References:
Schwab IR et al.; “Successful transplantation of bioengineered tissue replacements in patients
with ocular surface disease”; Cornea 19, 421-426; July 2000.

Tsai et al.; “Reconstruction of damaged corneas by transplantation of autologous limbal
epithelial cells.”; New England Journal of Medicine 343, 86-93, 2000.

Tsubota K et al.; “Treatment of severe ocular-surface disorders with corneal epithelial stem-cell
transplantation”; New England Journal of Medicine 340, 1697-1703; June 3, 1999

BLOOD AND LIVER DISEASE

Stem Cell- Rich Cord Blood Successfully Treats Often Fatal Blood Disorder
In a joint statement, doctors at Singapore's National Hospital and Singapore General Hospital
announced a "medical first" in transplanting umbilical cord blood from a non-related donor to
successfully treat thalassaemia. Thalassaemia is a hereditary blood disorder that often causes
severe anemia and is usually fatal to children if untreated. The statement noted that umbilical
cord blood is rich in "haemopoietic stem cells" from which the different types of blood cells
evolve.
Reference:
"SCH scores another first in stem cell transplants," Singapore General Hospital,
www.sgh.com.sg/
"Singapore scores medical first in treatment of thalassaemia," Agence France Presse, Aug. 14,
2001

4-month-old girl received stem cell transplant after receiving living-related liver transplant from
same donor (mother). Four months after stem cell transplant the patient was disease-free,
complete donor chimerism in bone marrow and stable hepatic function without any
immunosuppressive therapy.
Reference:
Matthes-Martin S et al.; “Successful stem cell transplantation following orthotopic liver
transplantation from the same haploidentical family donor in a girl with hemophagocytic
lymphohistiocytosis”; Blood 96, 3997-3999; Dec 1, 2000

Primary amyloidosis is a plasma cell disorder in which deposits of amyloid protein cause
progressive organ failure; most common target is the kidney, although heart, liver, and
nervous tissue effects are also seen. Compared to standard treatments, high-dose
chemotherapy with autologous peripheral blood stem cell transplantation is shown to be
much more effective in the clinical condition of patients.
Reference:
Sezer O et al.; “Novel approaches to the treatment of primary amyloidosis”; Exper Opin.
Investig. Drugs 9, 2343-2350; Oct. 2000

GENE THERAPY

*First successful trial of human therapy, re- injecting the infants’ own bone marrow stem cells
containing a normal copy of the gene that they lacked.
Reference:
Cavazzana-Calvo M et al.; “Gene therapy of human severe combined immunodeficiency
(SCID)-X1 disease”; Science 288, 669-672; April 28, 2000

HEART DAMAGE

Successful treatment of heart disease using adult stem cells
Doctors in Germany reported the successful use of a patient’s own adult stem cells from bone
marrow for regenerating tissue damaged after a heart attack. They injected the man’s own bone
marrow stem cells into his damaged heart muscle. Ten weeks after treatment, the damaged area
of heart tissue had been reduced, replaced by new cells, and the function of the patient’s heart
had increased by 20-30 %. The authors note that their results demonstrate that “transplantation
of human autologous adult stem cells is possible under clinical conditions and that it can lead to
regeneration of the myocardial scar after… infarction.” They also point out that the therapeutic
benefits can be ascribed to the adult stem cells. They plan to perform the same operation on 20
more patients in the coming months. The use of the patient’s own adult stem cells from bone
marrow or muscle to treat damage from heart attack is also in clinical trials in France and the
U.S. (Reuters Health, July 23, 2001)
Reference:
Strauer BE et al.; “Myocardial regeneration after intracoronary transplantation of human
autologous stem cells following acute myocardial infarction”; Dtsch Med Wochenschr 126, 932-
938; Aug 24, 2001

First successful human stem cell treatment for heart disease uses adult stem cells
The first reports of successful treatment for heart disease using the patient’s own adult muscle
stem cells are encouraging news regarding therapy after heart attack. French physicians
implanted skeletal muscle stem cells back into the patient; the encouraging result after eight
months’ follow- up underlines the potential of this new approach using adult stem cells. Further
clinical trials are now underway in Europe and the U.S. for other patients with heart disease. No
embryonic stem cells have ever been reported to be used in human trials.
A review of potential heart treatments notes that cell transplantation is a potential therapeutic
approach for patients with chronic heart failure. Experimental transplantation of muscle cells
showed that the grafted cells can functionally integrate with and augment the function of the
recipient heart. The scientists note that skeletal stem cells are abundant and can be grafted
successfully into the animal’s own heart even after genetic manipulation in vitro.
References:
Menasché P et al. “Myoblast transplantation for heart failure.” Lancet 357, 279-280; Jan 27,
2001
Menasché P et al. [“Autologous skeletal myoblast transplantation for cardiac insufficiency. First
clinical case.”] [article in French] Arch Mal Coeur Vaiss 94(3), 180-182; March 2001
“Doctor Puts Arm Muscle Cells Into Patient's Heart”, Associated Press, May 30, 2001
“First Percutaneous Endovascular Case of Heart Muscle Regeneration Completed with
Bioheart's MyoCell(TM) Product”, PRNewswire, May 30, 2001.
El Oakley RM et al.; “Myocyte transplantation for cardiac repair: A few good cells can mend a
broken heart”; Annals of Thoracic Surgery 71, 1724 –1733; 2001

General References Related to Clinical Uses of Adult Stem Cells
Recent studies have revealed that much of this remarkable developmental potential of embryonic
stem cells is retained by small populations of cells within most tissues in the adult. Intercellular signals that control the proliferation, differentiation and survival of stem cells are being identified and include a diverse array of growth factors, cytokines and cell adhesion molecules. Intracellular mechanisms that regulate stem cell fate are also emerging and include established second messenger pathways, novel transcription factors and telomerase. The possibility that a decline in the numbers or plasticity of stem cell populations contributes to aging and age-related disease is suggested by recent findings. The remarkable plasticity of stem cells suggests that endogenous or transplanted stem cells can be 'tweaked' in ways that will allow them to replace lost or dysfunctional cell populations in diseases ranging from neurodegenerative and hematopoietic disorders to diabetes and cardiovascular disease.
Reference:
Rao MS and Mattson MP; “Stem cells and aging: expanding the possibilities”; Mech Ageing
Dev 122(7), 713-734; May 31, 2001

Mesenchymal stem cells (MSCs) are the first non-hematopoietic progenitors to be isolated from
the bone marrow and extensively characterized. In addition to their ability to support hematopoiesis, MSCs can differentiate into osteocytes, chondrocytes, tenocytes, adipocytes and smooth muscle cells. This article will review our current understanding of bone marrow stroma and MSCs and their potential therapeutic role in the setting of hematopoietic stem cell transplantation.
Reference:
Koc ON and Lazarus HM; “Mesenchymal stem cells: heading into the clinic”; Bone Marrow
Transplant 27(3), 235-239; Feb. 2001

It appears that basal haematopoiesis is maintained throughout life, yet, the capacity to cope with
haematological stress is decreased in advanced age. In principle, stem cells derived from aged donors can be used for autologous transplantation, when needed to recover basic haematopoiesis. Current methods for expansion and maintenance of stem cells in vitro
enable examination of stem cell potential for long-term expansion and function. Understanding of the mechanisms underlying these processes will enable the fidelity of stem cell expansion and maintenance of their potential for long-term function.
Reference:
Globerson A; “Haematopoietic stem cell ageing”; Novartis Found Symp 235, 85-96; discussion
96-100, 101-4; 2001

This study examined whether cryopreservation following expansion has a detrimental effect on
the ability of cells to engraft, using the NOD-SCID mouse model. Cord blood (CB)
CD34(+) cells were incubated for 7 days with stem cell factor (SCF), flt-3 ligand (FL),
and megakaryocyte growth and development factor (MGDF). Expanded CD34(+) cells
were transplanted into NOD-SCID mice either fresh or following cryopreservation and
thawing. Thawed expanded CD34(+) cells had significantly higher SCID Engrafting
Potential (SEP) than freshly expanded CD34(+) cells. Results suggest that prior
cryopreservation does not prevent expanded cells engrafting in NOD-SCID mice.
Reference:
Rice AM et al.; “Prior cryopreservation of ex vivo-expanded cord blood cells is not detrimental
to engraftment as measured in the nod-scid mouse model”; J Hematother Stem Cell Res
0(1), 157-165; Feb. 2001

Represents the first case of successful transplantation of PBSC, cryopreserved twice and purged
after cryopreservation. Indicates that purging procedures can successfully be carried out
with cryopreserved cell material and that purified CD34+ cells can be cryopreserved a
second time before transplantation, without affecting their hematopoietic capacity.
Reference:
Humpe A et al.; “Successful transplantation and engraftment of peripheral blood stem cells after
cryopreservation, positive and negative purging procedures, and a second
cryopreservation cycle”; Ann Hematol 80(2), 109-112; Feb. 2001

General review of growth factors using in hematopoietic stem cell transplants. Recently, EPO
has been shown to significantly accelerate hematopoietic reconstitution after peripheral
blood stem cell transplantation (PBSCT) resulting in reduced infection rates. Both, GCSF
and GM-CSF have been shown, in numerous trials, to shorten the period of
chemotherapy-induced neutropenia, with reduction in attendant morbidity and to mobilize PBSC. In addition, administration of both cytokines after PBSCT significantly reduced the use of antibiotics and duration of hospitalization suggesting an economic benefit.
Reference:
Dempke W et al.; “Human hematopoietic growth factors: old lessons and new perspectives”;
Anticancer Res 20(6D), 5155-5164; 2000 Nov-Dec

Review of increasing use of umbilical cord blood for transplants; banking of cells, etc.
Reference:
Surbek DV and Holzgreve W; “Fetal cells from cord blood as stem cell source: current status and
possible implications in gynaecologic oncology”; Eur J Gynaecol Oncol 22(1), 6-12;
2001

Mobilized peripheral blood progenitor cells (PBSC) are increasingly being used instead of bone
marrow for allogeneic transplantation. This article gives a concise and clinically oriented
overview on current results and perspectives of allogeneic peripheral blood stem cell
transplantation, with particular focus on reconstitution of hematopoiesis and the immune
system, graft-versus-host disease, graft- versus-leukemia effects, intensity-reduced
conditioning, and graft engineering.
Reference:
Dreger P and Schmitz N; “Allogeneic transplantation of blood stem cells: coming of age?”; Ann
Hematol 80(3), 127-136; March 2001

Previously reported human stem cell frequencies and their in vivo self- renewal activity have
been markedly underestimated.
Reference:
Cashman JD and Eaves CJ; “High marrow seeding efficiency of human lymphomyeloid
repopulating cells in irradiated NOD/SCID mice”; Blood 96, 3979-3981; Dec. 1, 2000

Evidence for expansion protocol to maintain cord blood stem cells for clinical applications.
Reference:
Kobari L et al.; “In vitro and in vivo evidence for the long-term multilineage (myeloid, B, NK,
and T) reconstitution capacity of ex vivo expanded human CD34(+) cord blood cells”;
Exp Hematol 28, 1470-1480, December 2000

Study notes that disease recurrence is lower after peripheral blood stem cell transplants than with
bone marrow; “The general opinion is that peripheral blood grafts are indicated for
patients with advanced disease, whereas for patients with early-phase disease the two
sources may give comparable results.”
Reference:
Bacigalupo A et al.; “Bone marrow or peripheral blood as a source of stem cells for allogeneic
transplants”; Curr. Opin. Hematol. 7, 343-347; Nov. 2000

Quality of life for 415 adult patients who received hematopoietic stem cell transplants was
measured; typical patients can look forward to a quality of life after transplantation that is
broadly comparable to that of the normal population.
Reference:
Bush NE et al.; “Conditional and unconditional estimation of multidimensional quality of life
after hematopoietic stem cell transplantation: a longitudinal follow- up of 415 patients”;
Biol. Blood Marrow Transplant 6, 576-591; 2000

Review of techniques to mobilize hematopoietic bone marrow stem cells into peripheral blood.
Reference:
Fu S, Liesveld J; “Mobilization of hematopoietic stem cells”; Blood Rev 14, 205-218; Dec. 2000

Technique to expand numbers of human hematopoietic stem cells in culture. Cells from
umbilical cord blood and adult patient peripheral blood were expanded with 2 factors, flt-
3 ligand and thrombopoietin/c-mpl ligand, and maintained for prolonged periods (up to
16 weeks), and sufficient numbers were generated for adult transplantation.
Reference:
Gilmore GL et al.; “Ex vivo expansion of human umbilical cord blood and peripheral blood
CD34(+) hematopoietic stem cells”; Exp. Hematol. 28, 1297-1305; Nov. 1, 2000

Review of records for cord blood stem cell transplants. Results showed survival comparable to
bone marrow transplants. “This large registry study confirms the potential benefit of
using umbilical cord blood hematopoietic stem cells for allogeneic transplants.”
Reference:
Gluckman E; “Current status of umbilical cord blood hematopoietic stem cell transplantation”;
Exp. Hematol. 28, 1197-1205; Nov. 1, 2000

Review of potentials for stem cell transplantation.
Reference:
Steward CG; “Stem cell transplantation for non- malignant disorders”; Baillieres Best Pract. Res.
Clin. Haematol. 13, 343-363; Sept. 2000
Slavin S; “new strategies for bone marrow transplantation”; Curr. Opin. Immunol. 12, 542-551;
Oct. 2000

Improved technique to quickly expand numbers of cord blood cells in culture, allowing adequate
numbers for treatment of adult patients.
Reference:
McNiece I et al.; “Increased expansion and differentiation of cord blood products using a twostep
expansion culture”; Exp. Hematol. 28, 1181-1186; Oct. 2000

“Can expand primitive hematopoietic progenitors from Cord Blood and Peripheral Blood and
expanded cells retain the capacity for myeloid and lymphoid differentiation. These
findings emphasize the importance of assessing multi- lineage differentiation capacity
following ex- vivo expansion.
Reference:
Lewis ID, Verfaillie CM; “Multi- lineage expansion potential of primitive hematopoietic
progenitors. Superiority of umbilical cord blood compared to mobilized peripheral
blood”; Exp. Hematol. 28, 1087-1095; Sept. 1, 2000

Generating a high frequency of clonally repopulating stem cells from blood.
Reference:
Cho RH, Muller-Sieburg CE; “High frequency of long-term culture-initiating cells retain in vivo
repopulation and self-renewal capacity”; Exp. Hematol. 28, 1080-1086; Sept. 1, 2000

Jacobs P et al.; “Allogeneic stem cell transplantation. An economic comparison of bone marrow,
peripheral blood, and cord blood technologies”; Int. J. Technol. Assess Health Care 16,
874-884; Summer 2000

Autologous (same patient) circulating blood stem cell transplants show faster recovery, less
transplant problems, shorter hospital stay, and reduced cost compared to bone marrow
transplants.
Reference:
“Overview of autologous stem cell transplantation”, Saba, N et al., Critical Reviews of
Oncology and Hematology 36, 27-48, October 2000.

Allogeneic peripheral blood stem cell transplants as good or better than bone marrow.
Reference
Ringden O et al., “Peripheral blood stem cell transplantation from unrelated donors: a
comparison with marrow transplantation”, Blood 94, 455; July 15, 1999

Reviews of current protocols allowing better methods for collection of stem cells from peripheral
blood.
References:
Hester J; “Peripheral blood stem cell collection: the interaction of technology, procedure, and
biological factors”; Transfus. Sci. 23, 125-132; Oct. 2000
Kessinger A; “Collection of autologous peripheral blood stem cells in steady state”; Baillieres
Best Pract. Res. Clin. Haematol. 12, 19-26; Mar-Jun, 1999
Korbling M; “In vivo expansion of the circulating stem cell pool”; Stem Cells 16 Suppl 1, 131-
138; 1998.
Kessinger A, Sharp JG; “Mobilization of blood stem cells”; Stem Cells 16 Suppl 1, 139-143;
1998

Review of cord blood stem cell transplants
Reference:
Huhn RD; “Umbilical cord blood stem cell transplantation and banking”; N J Med 97, 53-57;
Sept. 2000

“Bibliography. Current world literature. Hematopoietic stem cell transplantation”; Curr. Opin.
Hematol. 7, B171-189; Nov. 2000

Treating Parkinson’s with Adult Stems Cell and Other Alternatives

Using adult neural stem cells, Dr. Michel Levesque, at the Cedars-Sinai Medical Center in Los Angeles, reports a total reversal of symptoms in the first Parkinson’s patient treated. The patient, a 57-year old former fighter pilot, is still without symptoms three years after the adult neural stem cells were removed from his brain, coaxed into becoming dopamine-producing cells, and then reimplanted. Because the stem cells came from the patient, there was no need for immunosuppression to overcome rejection. "I think transplantation of the patient's own neural stem cells and differentiated dopaminergic neurons is more biologically and physiologically compatible - more efficacious and more elegant," said Levesque. In addition to its use for Parkinson’s, the technique is under study for juvenile diabetes, stroke, brain tumors, spinal cord injury, and other conditions.
Reference:
Results presented April 8th, at the meeting of the American Association of Neurological Surgeons.

Retinal Cell Implants Improve Parkinson’s
A team at Emory University School of Medicine has shown that implanting retinal cells into the brains of people with advanced Parkinson's disease can improve motor function by almost half, according to a follow-up study of six patients. The team noted: "We've been following these six participants for over a year, and we've found they've improved, on average, nearly 50 per cent in motor function." The retinal cells used were taken from deceased donors and grown in the lab. The team is not using immunosuppressants.
Reference:
Result presented April 18 at the annual conference of the American Academy of Neurology in Denver and reported in the New Scientist , April 18, 2002.

N.B: There are no clinical treatments for Parkinson’s based on cloning or embryonic stem cells.

Adult Skin Cells Reprogrammed Without Cloning
A team of scientists from Norway has succeeded in coaxing one type of adult cell to start behaving like a completely different type of adult cell. The scientists have made human skin cells in a test tube behave as if they were immune system cells, by bathing the skin cells in extracts of the immune cells. In other work, they have been able to get skin cells to behave as if they were nerve cells.
"We can take a skin cell from your body and turn it directly into a cell type that you need to treat a particular disease," said Dr. Philippe Collas, the leader of the team, whose work was published 5/1/02 in the respected journal Nature Biotechnology.

The technique being developed would allow skin cells from a patient to be turned directly into other types of cells without having to revert first to an embryonic state and without needing women's eggs. They told Reuters, "That's the beauty of our system -- we are not working with embryos or dealing with stem cells at all. You get around all these issues." "It would be a one-day procedure, in principal. The patient would come in and give a skin biopsy to the lab to reprogram and the day after you could put the cells back into the patient." The technique would have immediate applications in cancer. The group is also looking at making insulin-secreting pancreatic cells.

The approach will aid investigation of the mechanisms by which adult stem cells revert to cells capable of differentiating into other types of cells with potential use in therapies for conditions like diabetes, Parkinson's disease, and heart disease. From a clinical perspective, approaches based on this technology would allow replacement cells to be generated that are compatible with a patient's immune system, without the ethical problems of generating or destroying embryos.

Reference:
A.M. Hakelien et al.; "Reprogramming fibroblasts to express T-cell functions using cell extracts;" Nature Biotechnology 20, 460-466; May 2002

Adult Bone Marrow Stem Cells Transformed Into Functional Liver Cells
Dr. Catherine Verfaillie’s group at Minnesota continues to show more and more uses for the multipotent adult progenitor cells (MAPC) from bone marrow. The team has now shown that these adult stem cells can transform into functional liver cells. The adult stem cells also were grown in culture for over 100 generations, twice the length of time previously thought possible with adult cells.
Reference:
R. E. Schwartz et al.; "Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells;" J. Clin. Invest. 109,1291–1302; May 2002

“Therapeutic” Cloning No Longer Needed, Says Leading Embryonic Stem Cell Scientist
Alan Trounson, Australian embryonic stem cell expert and a leader in the field worldwide, says that stem cell research (both adult and embryonic) has advanced so rapidly in the past few months that therapeutic cloning is now unnecessary. “My view is there are at least three or four other alternatives that are more attractive already,” he said. Professor Trounson said therapeutic cloning faces logistical problems, and that other techniques are showing great promise and offer better options.
References:
Tom Noble, “Stem-cell cloning not needed, says scientist,” The Age (Melbourne), pg. 2, July 29, 2002.
Jim Buckell, “Stem-cell research outpaces cloning,” The Australian, pg. 3, July 29, 2002.
“Therapeutic cloning no longer necessary: expert,” AAP Newsfeed, July 29, 2002.

Adult Stem Cells More Effective Than Embryonic Stem Cells in Blood Formation
Because hematopoietic (blood forming) stem cells (HSCs) can restore and maintain blood formation following transplantation into immune deficient hosts, growth of HSCs in culture is important for many clinical applications. Previously, researchers in Sweden used a gene therapy technique to add a growth gene to embryonic stem cells to get adequate growth in culture. According to the authors, however, “HSCs of early embryonic origin, including those derived from differentiated embryonic stem cells, are inefficient in engrafting adult recipients upon transplantation.” The researchers have now shown that adding the same growth gene, Lhx2, to adult bone marrow stem cells allows unlimited growth of the cells. These adult stem cells efficiently rescued immune-compromised mice and generated all blood cells.
Reference:
Ó. P. do Pinto et al.; “Hematopoietic progenitor/stem cells immortalized by Lhx2 generate functional hematopoietic cells in vivo”; Blood 99, 3939-3946; June 1, 2002

Adult Bone Marrow Stem Cells Show Immune Tolerance, Not Rejected
Researchers in Canada and Japan have shown in animal studies that adult stem cells from bone marrow have a unique immunity tolerance. When selected bone marrow stem cells of mice were injected into rats, without immunosuppression, the injected cells survived and thrived without being rejected by the host immune system. The cells incorporated not only into bone marrow but also into damaged heart to aid repair.
Reference:
T. Saito et al.; “Xenotransplant cardiac chimera: immune tolerance of adult stem cells”; Annals of Thoracic Surgery 74, 19-24; July 2002

Adult stem cells stimulated to form insulin-secreting pancreatic cells
Scientists at Massachusetts General Hospital have successfully turned adult stem cells into insulin-producing cells that could reverse diabetes. They found that treating adult stem cells in the pancreas with a naturally occurring hormone can transform the stem cells into beta cells, which secrete insulin. This means new beta cells could be made from a patient’s own pancreatic stem cells to treat their diabetes.
Reference:
E.J Abraham et al.; “Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells”; Endocrinology 143, 3152-3161; August 2002

Adult Bone Marrow Stem Cells Can Repair Retina
Adult bone marrow stem cells injected into the eyes of rats with damaged retinas formed new retinal cells. The bone marrow stem cells incorporated and differentiated into retinal neural cells in the injured retina. Bone marrow stem cells may be useful in repair of damaged retinal cells.
Reference:
M. Tomita et al.; “Bone marrow-derived stem cells can differentiate into retinal cells in injured rat retina”; Stem Cells 20, 279-283; July 2002

Adult Bone Marrow Stem Cells Could Prevent Blindness, Grow New Blood Vessels
Scientists at Scripps Research Institute used bone marrow stem cells to grow new blood vessels in the eyes of mice, a development researchers say could lead to treatments for some forms of blindness in humans, including diabetic retinopathy and macular degeneration. The injected adult stem cells homed in on the parts of the eye where they were needed, grew new blood vessels, and prevented blindness in the mice. Diabetic retinopathy is the leading cause of blindness in working age Americans, and age-related macular degeneration is a common cause of vision loss in people over age 60. Both conditions are caused by damaged retinal blood vessels.
Reference:
A. Otani et al.; “Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis”; Nature Medicine published online, www.nature.com; doi:10.1038/nm744; July 29, 2002

Adult Bone Marrow Stem Cells Stimulate Growth in Children With Bone Disease
Adult bone marrow stem cells implanted into children with osteogenesis imperfecta, a severe bone and cartilage disease, have stimulated growth of bone in these patients. During the 6 months immediately following the transplant, the children’s growth reached 60% to 94% of expected normal values for children their age.
Reference:
Horwitz EM et al.; “Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone”; Proc Natl Acad Sci USA 99, 8932-8937; June 25, 2002

Information on this page compiled from www.stemcellresearch.org