Epigenetically Reprogrammed Cells Generate Functional Cord Blood Stem Cells for Transplantation
The use of cord blood cells as hematopoietic stem cell grafts for patients with hematologic malignancies receiving an allogeneic stem cell transplant has been limited to children due to the small number of stem cells present in a single cord blood collection. The result of these limitations has been a high rate of graft failures in adult patients.
To overcome these limitations, researchers from the Icahn School of Medicine at Mount Sinai in New York City treated CD34-positivecells with a combination of histone deacetylase (HDAC) inhibitors and valproic acid. They found that the treated cells produced a greater number of repopulating cells, and established multilineage hematopoiesis in primary, secondary, and tertiary immune-deficient mice. The findings may provide clinical benefit for adults with leukemia, lymphoma, and other blood cancers. The study is published in The Journal of Clinical Investigation.
Study Methods and Results
The researchers treated dividing cord blood CD34-positive cells ex vivo with several HDAC inhibitors. They found that after an initial 16-hour cytokine priming, the cells treated with the most active HDAC inhibitor, valproic acid, increased the number of multipotent (CD34-positive and CD90-positive) cells that were generated. However, the increase was substantially greater in the presence of both valproic acid and cytokines for 7 days.
Compared with the cord blood CD34-positive cells, the valproic acid–treated CD34-positive cells produced a greater number of severe combined immunodeficiency–repopulating cells and established multilineage hematopoiesis in primary and secondary immune-deficient recipient mice. The data indicate that greater numbers of functional cord blood stem cells can be generated by epigenetically reprogramming dividing cord blood CD34-positive cells with valproic acid, according to the study.
“We’re excited by these results,” study coauthor Ronald Hoffman, MD, of the Tisch Cancer Institute at Mount Sinai, said in a statement. “The findings have important implications for patients battling blood cancers and the difference between success and failure of lifesaving stem cell transplants.”
Dr. Hoffman and Pratima Chaurasia, PhD, of the Tisch Cancer Institute at Mount Sinai, are the corresponding authors for The Journal of Clinical Investigation article.
Funding for this study was supported by a grant from the Empire State Stem Cell Board. The study authors reported no conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
