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Retinoic Acid Pathway Inhibition To Expand Human Hematopoietic Progenitor Cells With Islet Regenerative Capacity, Ruth Elgamal

Electronic Thesis and Dissertation Repository

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 …}