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

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 (ALDHhi) reduce hyperglycemia after transplantation into streptozotocin (STZ)-treated NOD/SCID mice. However, UCB-derived ALDHhi 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 ALDHhi cells for therapy. ALDHhi cells expanded for 6 days with BMS 493 showed a 2.70-fold-increase in ALDHhi 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.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Physiology and Pharmacology

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2017

Author dc:creator

• Elgamal, Ruth

Advisor dc:contributor.advisor

• David Hess

• Diabetes
• Stem Cells
• Islet Regeneration
• Retinoic Acid

Language dc:language.iso

en_ca

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/27536

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/27536