Stem Cell Therapy Debate Lives On

Stem Cell Therapy Debate Lives On, but Research Continues to Find Effective Applications in Immune and Organ Function
Sunday December 10, 10:00 am ET

ORLANDO, Fla., Dec. 10 /PRNewswire/ — While the debate over the ethical implications of stem cell research continues to embroil medical and political communities, researchers are successfully demonstrating the therapeutic value of human stem cells in a wide variety of diseases. Three studies being presented today at the 48th Annual Meeting of the American Society of Hematology (ASH(TM)) suggest that the use of stem cells may improve the treatment of life-threatening diseases while simultaneously decreasing complications from therapy.

“We know that stem cells may be the key to developing more effective and less toxic therapies to fight a host of diseases in the future,” said Stephen Emerson, MD, PhD, of the University of Pennsylvania, Philadelphia. “While we are working together to determine the best way to extract these cells without causing any human harm, continued research — like the studies presented here — offers a significant benefit by identifying the many possible applications of this therapy.”

Several of the studies being presented review stem cell therapy in relation to the transplantation process, which can result in a variety of complications based on the donor’s relation to the recipient. The outcomes of related and unrelated donor cell transplants depend heavily on the degree of human leukocyte antigen (HLA) matching between the transplant recipient and the donor. Matching HLA is extremely important to successful engraftment, frequency and severity of graft-versus-host disease (GVHD), and overall survival post-transplant. A haploidentical transplant uses cells from a relative who is not HLA-matched but who has common related genes with the recipient, including parents and sometimes siblings. For patients with an urgent transplant need and without identical HLA-matched relatives, a haploidentical match is often the next best option.

Mesenchymal Stem Cells for Treatment of Severe Acute Graft-Versus-Host Disease [Abstract #753]

Research in stem cell therapy has expanded to a variety of diseases as researchers discover the value of human stem cells in treating illnesses like cancer and heart disease. In this study, a team of researchers from Sweden examined the value of stem cell therapy for severe graft-versus-host disease (GVHD), a major complication of blood transplants that replace damaged cells due to leukemia and other disorders. During successful transplants, the donated cells engraft or implant within the patient’s bone marrow, where they grow and provide a new source of blood and immune cells. GVHD occurs when T- cells from the donor (the graft) respond to the host cells in the patient’s body as foreign and attack them.

A total of 40 patients with severe (grades III-IV) acute GVHD were given varying doses of therapy with mesenchymal stem cells (MSC), derived from bone marrow: one dose (19 patients), two doses (19 patients), three doses (2 patients), or five doses (2 patients). The stem cells were donated from HLA- identical sibling donors (5), haploidentical donors (19), and HLA-mismatched donors (41).

The results of the trial therapy were successful overall, as 19 patients experienced a complete response and nine additional patients showed some improvement. The disease stabilized in four patients but did not improve. In seven patients the treatment did not provoke a response, and one patient was not evaluated due to short-term participation. No side effects were seen after the MSC infusions. The team has continued to follow up with patients (up to 3.5 years); of the 21 surviving patients, nine have chronic GVHD, one patient has recurrent leukemia, and one has de novo AML.

“Based on the results of this study, we are optimistic that mesenchymal stem cells do in fact have measurable value in repairing human tissues,” said Katarina LeBlanc, MD, PhD, of the Karolinska University Hospital Huddinge, Stockholm, Sweden, and lead author of the study. “This therapy should be further explored in randomized trials as an effective and safe way to treat severe acute GVHD.”

Offering explanation for the possible value of MSCs in treating GVHD, researchers noted that MSCs derived from adult bone marrow have the capacity to differentiate into several types of mesenchymal tissue and are proven to inhibit T-cell alloreactivity in vitro. Therefore, the disease characteristic of attacking the host body’s cells is blocked by the injection of these stem cells.

Long-Term Safety and Efficacy of Stem Cell Gene Therapy for ADA-SCID [Abstract #200]

Severe combined immunodeficiency (SCID) is caused by a severe genetic defect often found in newborns. Because the immune system is so severely compromised, exposure to even benign germs can result in serious or life- threatening infections like pneumonia, meningitis, or bloodstream infections. The condition must be diagnosed and treated quickly to prevent serious complications, and doctors continue to struggle with often ineffective treatment options. In this study, a team of Italian researchers found that the use of stem cells may effectively fight SCID caused by a deficiency of the ADA gene (adenosine deaminase), which is critical for the immune system to function properly.

Previous research has shown that immune function has improved when patients were given an autologous hematopoietic stem cell transplant (HSC), from the body’s own bone marrow, combined with the ADA gene. The current phase I/II study treated eight ADA-SCID children (ages 7-67 months) with HSC conditioned with busulfan, a treatment that helps with the engraftment process. After following patients for an average of three years, researchers have seen no adverse events related to the gene transfer. In fact, they have observed that the stem cells have successfully integrated into the patients’ marrow, giving rise to genetically repaired blood cells.

In the six children with a follow-up of more than one year, white blood cell counts progressively increased and T-cell functions normalized. In addition, tests found the presence of antigen-specific antibodies (proteins that help the immune system identify and fight bacteria and viruses). In five patients, levels were high enough to discontinue supplemental antibody treatment.

“We feel that these data confirm the safety and efficacy of gene therapy in improving immune and metabolic function in children diagnosed with this form of severe combined immunodeficiency,” said Alessandro Aiuti, MD, of the San Raffaele Telethon Institute for Gene Therapy in Italy and lead author of the study with Maria Grazia Roncarolo, MD. “This may represent a viable solution to reduce the mortality rates associated with SCID in newborns.”

At the conclusion of the study, all participants were healthy, with no severe infections, up to six years from the treatment. Researchers noted that because the ADA genes had sustained activity in the blood cells, the children’s growth and development has continued to improve.

The treatment is funded by the Italian non-profit Telethon Foundation, a major charity that raises and distributes funds in Italy for biomedical research on genetic diseases, and has recently attained Orphan Drug status from the European Medicines Agency (EMEA).

Cord Blood Mesenchymal Stem Cells for Acute Renal Failure Repair [Abstract #282]

As scientists continue to discover new applications for human stem cells, they are targeting diseases with a significant need for more efficacious treatment options. Until recently, pharmacologic therapies for acute renal failure have been generally unsuccessful, so the potential therapeutic value of mesenchymal stem cells (MSCs) is particularly intriguing.

In this study, a team of researchers in Italy obtained MSCs from full-term umbilical cord blood to test their therapeutic value on renal tissue in mice with acute renal failure. The team successfully isolated MSCs from approximately 18 percent of the processed cord blood units, confirming the rate obtained by other stem cell studies. Testing of the MSCs also confirmed certain characteristics that help induce tissue repair, like the development of bone and cartilage.

Ten immunocompromised mice with acute renal failure received either cord blood MSCs or intravenous saline (control) and were evaluated for renal function and histology. Renal tissue was evaluated at day four and assigned a score (0-3) measuring the level of damage.

The MSCs significantly protected the mice from renal function impairment at day four, which was noted by reduced levels of blood urea nitrogen (a waste byproduct caused by kidney malfunction) from 115 mg/dl (saline) to 64 mg/dl (MSCs). Tissue damage was also reduced in the stem cell-treated mice (score of 0.5) compared to saline-treated mice (score of 1.0) as demonstrated by Marina Morigi, PhD, of Mario Negri Institute of Pharmacological Research in Bergamo, Italy, who conducted the in vivo study.

“These preliminary results indicate that human mesenchymal stem cells do exhibit reparative potential in acute renal failure,” said Lorenza Lazzari, PhD, of the Cell Factory, Department of Regenerative Medicine at Fondazione Policlinico in Milano, Italy, and lead author of the study. “With more evidence demonstrating their value in human subjects, the unique therapy of human stem cells may offer patients with renal failure a safer and more effective way to combat the illness.”

This study was sponsored by European Community.

The American Society of Hematology ( is the world’s largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology.



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