Melissa Mahoney, Ph.D. - Account Profile
Recent advances in the treatment of juvenile-onset diabetes include islet transplantation; however, this therapy is limited in application by the shortage of donor islets available for grafting. Motivated by the potential benefits of this therapy for millions of patients, researchers have begun looking for a sustainable source of islets. Pancreatic precursor cells are of interest in this endeavor because they are proliferative and have the potential to become any cell type found in the mature pancreas, including insulin-secreting beta cells, the major component of islet tissue that tends to die in patients. While promising, techniques to reproducibly expand and differentiate pancreatic precursor are lacking. Extracellular matrix molecules and growth factors, key regulators of precursor cell function in other organ systems are present in the developing pancreas, however their role in controlling pancreas development is not well studied, a problem that scientists in the field believe could be mitigated if better in vitro culture techniques were available.
In our approach, pancreatic precursor cells are cultured in a three-dimensional environment in which non-specific signaling cues from the 3D culture itself are minimal—polyethylene glycol (PEG)-based hydrogels. Key biological components of the developing pancreas extracellular environment are incorporated into 3D PEG hydrogels in a controlled manner. Within a PEG hydrogel, the effect of individual signaling molecules exogenously added into the hydrogel environment can be clearly elucidated, without the confounding effects that would be observed in a protein-based 3D matrix. Using a combination of gene expression analysis and immunocytochemistry chemical environments that promote (1) differentiation into insulin-producing beta cells, or (2) proliferation of multipotent pancreatic precursor cells which can be subsequently differentiated into insulin-producing beta cells are being identified. To sum, the focus of our work is to develop novel cell culture techniques to control pancreatic precursor expansion and differentiation. The resulting 3D hydrogels laden with insulin positive cells would be suitable for direct implantation into patients with Type I diabetes.
Scientific Interests/Keywords
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