Distinct Human Progenitor Subtypes Promote Islet Regeneration via Activation of Endogenous Angiogenic or Neogenic Programs
Date of Award
Master of Science
Physiology and Pharmacology
Dr. David Hess
Transplanted murine bone marrow (BM) progenitor cells stimulate endogenous beta cell proliferation and insulin production. To enrich for analogous human progenitor cells, we purified human umbilical cord blood (UCB) and BM based on high aldehyde dehydrogenase activity (ALDHhl), a conserved function in multiple progenitor lineages. Transplantation of ALDHhl mixed progenitor cells or culture- expanded multipotent stromal cells (MSC) into streptozotocin-treated NOD/SCID mice revealed endogenous islet regeneration occurred via distinct mechanisms. Transplantation of ALDHhl cells improved systemic hyperglycemia via increased islet vascularization and proliferation resulting in increased islet size, but not islet number. Contrary to mixed-progenitor cells, transplantation of cultured MSC stably reduced hyperglycemia via an increase in islet number directly associated with the ductal epithelium without evidence of NGN3+ endocrine precursor activation. Further understanding of these endogenous angiogenic or putative neogenic programs activated by distinct human progenitor subsets may provide new approaches for combinatorial cellular therapies to treat diabetes.
Bell, Gillian Irina, "Distinct Human Progenitor Subtypes Promote Islet Regeneration via Activation of Endogenous Angiogenic or Neogenic Programs" (2010). Digitized Theses. 3742.