Scientists in Drs. Hoffman and Chaurasia’s laboratories have developed a novel approach to substantially expand the numbers of functional Cord blood (CB) hematopoietic stem cells (HSCs) while maintaining true stem cell engraftment capability. Cord blood (CB) cells that express CD34 have extensive hematopoietic capacity and rapidly divide ex-vivo in the presence of cytokine combinations. However, many of these CB CD34+ cells lose their marrow-repopulating potential.
To overcome this functional decline, dividing CB-CD34+ cells were treated with histone deacetylase inhibitors (HDACI) valproic acid (VPA) for seven days using a serum-free (SF) culture system supplemented with a specific cytokine combination. Treated CD34+ cells were characterized based on the upregulation of pluripotency genes, increased aldehyde dehydrogenase activity, and enhanced expression of CD90, c-Kit (CD117), integrin alpha-6 (CD49f), and CXCR4 (CD184).
Compared with CB CD34+ cells, VPA-treated CD34+ cells produced a greater number of SCID-repopulating cells and established multilineage hematopoiesis in primary and secondary immune-deficient recipient mice. These data indicate that dividing CB CD34+ cells can be epigenetically reprogrammed by treatment with VPA so as to generate greater numbers of functional CB stem cells for use as transplantation grafts.
Current Development Status
- Pre-clinical
Applications
- Transplantation
Advantages
- Simple, reproducible protocol
Publications
- Chaurasia P, et al. “Epigenetic reprogramming induces the expansion of cord blood stem cells.” J Clin Invest. 2014 Jun 2;124(6):2378-95. doi: 10.1172/JCI70313. Epub 2014 Apr 24.
Patent Status
- International Application PCT/US2014/038361 filed May 16, 2014
- Status: Pending
Contact Information
Felipe Araujo, PhD
Director, Blue Mountain Technologies
Mount Sinai Innovation Partners | Icahn School of Medicine at Mount Sinai
Phone: 646.605.7304