Retinoic Acid Pathway Inhibition to Expand Human Hematopoietic Progenitor Cells with Islet Regenerative Capacity

Author

Ruth Elgamal, The University of Western OntarioFollow

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Dr. David Hess

Abstract

Cellular therapy to induce islet regeneration is emerging as a novel treatment strategy for diabetes. Umbilical cord blood (UCB)-derived hematopoietic stem/progenitor cells (HSPC) isolated by high aldehyde dehydrogenase activity (ALDH^hi) reduce hyperglycemia after transplantation into streptozotocin (STZ)-treated NOD/SCID mice. However, UCB-derived ALDH^hi cells are rare and expansion without the loss of regenerative function is required. We hypothesized that BMS 493, an inverse retinoic acid receptor agonist, will prevent HSPC differentiation of HSPC during expansion, generating more ALDH^hi cells for therapy. ALDH^hi cells expanded for 6 days with BMS 493 showed a 2.70-fold-increase in ALDH^hi cells compared to untreated cells. Conditioned media from BMS 493-treated cells also increased human ß-cell proliferation in vitro. However, intrapancreatic transplantation of BMS 493-treated cells did not reduce hyperglycemia in STZ-treated NOD/SCID mice. Further characterization of HSPC expansion without differentiation is required for islet regenerative therapies.

Recommended Citation

Elgamal, Ruth, "Retinoic Acid Pathway Inhibition to Expand Human Hematopoietic Progenitor Cells with Islet Regenerative Capacity" (2017). Electronic Thesis and Dissertation Repository. 4874.
https://ir.lib.uwo.ca/etd/4874