Date of Award


Degree Type


Degree Name

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.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.