Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology

Supervisor

Dr. David Hess

Abstract

Human umbilical cord blood (UCB) progenitor cells with high aldehyde dehydrogenase activity (ALDHhi), can stimulate endogenous islet regeneration after transplantation into mice with steptozotocin (STZ)-induced diabetes. However, UCB ALDHhi cell are extremely rare, and expansion will be required to develop cell-mediated strategies to treat patients with diabetes. To increase the number of progenitor cells available for clinical application, we expanded ALDHhi UCB cells under clinically applicable, serum-free hematopoietic-restricted conditions. 6 day expansion resulted in a 15-fold increase in total cell number, and a 3-fold increase in the number of HPC retaining high ALDH (ALDHhi HPC) activity. ALDHhi HPC highly expressed primitive hematopoietic cell surface markers, and demonstrated hematopoietic colony forming capacity in vitro. Culture expanded ALDHhi HPC transplanted STZ-treated mice demonstrated improved islet function, increased islet size, and vascularization. Therefore, culture expanded ALDHhi HPC represent a novel population for the development of cellular therapies to promote islet regeneration.

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