Study reveals potential for more efficient stem cell transplants

08/13/04

Indiana University School of Medicine study published in Science

Blood-making stem cells found in bone marrow, umbilical cord blood and some adult blood products have been used in transplants to treat cancers, leukemia and immune system disorders and to restore blood cell production compromised by chemotherapy and irradiation. But insufficient numbers of donor cells sometime limit success, especially with cord blood transplants.

An Indiana University School of Medicine study suggests these stem cells can be enhanced in trafficking to the bone marrow and may increase transplant success, particularly in adults. The study, "Modulation of Hematopoietic Stem Cell Homing and Engraftment by CD26," appears in the Aug. 13 issue of Science.

Hematopoietic stem cells, rich sources found in the umbilical cord and placenta, are precursors of mature blood cells. They have the ability to replace damaged or diseased bone marrow systems and can continue to produce mature blood cells. Bone marrow is found in soft fatty tissue inside bones, where red blood cells, white blood cells and platelets are produced and developed.

"The efficiency of hematopoietic stem cell transplantation is important when donor-cell numbers are limiting," says study co-author Hal E. Broxmeyer, Ph.D., Distinguished Professor and chair of the School's Department of Microbiology and Immunology. "Attempts at growing hematopoietic stem cells outside the body for clinical transplantation have not been encouraging."

Using a mouse model, the study sought an alternative means to enhance the engraftment of stem cells by increasing their homing capability to the bone marrow. IU researchers focused on CD26, an enzyme on the surface of stem cells. They inhibited or deleted the CD protein on donor cells and were able to boost short-term homing, long-term engraftment and hematopoietic stem cell repopulation.

"The results were revealing," says Dr. Broxmeyer. "By inhibiting or deleting CD26, it was possible to increase greatly the efficiency of transplantation. This indicates that improvement of stem cell transplants may be possble in the clinic."

The IU research team also included principal author Kent W. Christopherson, Ph.D., Giao Hangoc, D.V.M., and Charlie Mantel. All are affiliated with the Walther Oncology Center, which Dr. Broxmeyer directs.

Dr. Broxmeyer's laboratory research, which led to the use of umbilical cord blood for stem cell transplantation to treat a large number of malignant and non-malignant diseases, is internationally recognized.

He was a member of the team that successfully performed the first cord blood transplant in 1988 in France for a young boy suffering from Fanconi anemia, a pre-leukemic and often fatal disease. Dr. Broxmeyer's laboratory set up the world's first cord blood bank, which processed the blood for the first five cord blood transplants.

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