Expanding Functional Cord Blood Stem Cells for Transplantation

Patients who suffer from blood-based diseases such as leukemia, lymphoma, and other blood-related diseases sometimes require bone marrow transplants in order to live. The paucity of available bone marrow necessitates the use of umbilical cord blood for these patients, but cord blood suffers from one flaw and that is small volumes of blood and low numbers of stem cells. Scientists have tried to grow cord blood stem cells in culture in order to beef up the numbers of stem cells, but cord blood stem cells sometimes lose their ability to repopulate the bone marrow while in culture.

To solve this problem, researchers at the Icahn School of Medicine at Mount Sinai have designed a new technique to expand the number of cord blood stem cells without causing any loss of potency.

“Cord blood stem cells have always posed limitations for adult patients because of the small number of stem cells present in a single collection,” said Partita Chaurasia of the Tisch Cancer Institute at Mount Sinai. “These limitations have resulted in a high rate of graft failure and delayed engraftment in adult patients.”.

Chaurasia and coworkers used a technique called “epigenetic reprogramming” to reshape the structure of the genome of the stem cells. They used a combination of a drug called valproic acid and histone deacetylase inhibitors (HDACIs). The valproic acid-treated cells produced greater numbers of marrow repopulating stem cells in culture. These expanded cord blood stem cells were also able to reconstitute the bone marrow of immune-deficient mice, and when the reconstituted bone marrow of that mouse could be used to reconstitute the bone marrow of another immune-deficient mouse. Bone marrow from this second mouse could also reconstitute the bone marrow of a third immune deficient mouse.

These results have extremely important implications for patients who are in the midst of a battle with blood cancers, and might mean the difference between a successful cord blood transplant and one that fails.