Title:Small Molecule-induced Beta-cell Regeneration from Alternate Cell Sources
VOLUME: 1 ISSUE: 1
Author(s):Kai Hui Hu He, Tamara J. Gilbert, Dina Fomina-Yadlin and Bridget K. Wagner
Affiliation:Chemical Biology Program, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA.
Keywords:Small molecules, beta cells, stem cells, cell therapy, type 1 diabetes, insulin, alpha cells, pancreatic islets, pregnancy, adenoviruses.
Abstract:Restoring functional pancreatic beta-cell mass in patients with type 1 diabetes would achieve insulin independence,
and ultimately improve quality of life. Historically, animal models have represented the majority of work done to
understand beta-cell regeneration. The outcomes of such studies have provided important insights on genetic approaches
to replenish beta-cell mass, but these genetic perturbations limit the suitability of such methods for clinical purposes. An
alternate discovery path involves the use of beta cells from stem-cell sources. Recent advances in the stem-cell field demonstrate
the possibility of inducing pluripotent stem cells from somatic cells and subsequently differentiating them into
beta cells, but these derived cells also face important barriers to their use. Pancreatic alpha cells represent an alternative
cellular source, and mouse studies show that there is ample capacity for beta-cell reprogramming. For all of these cell
sources, chemical compounds have several advantages over genetic approaches, in terms of their convenience of use and
provision for temporal control, and represent a promising avenue to attain insulin independence. We present in this review
the prospects of using small molecules to induce beta-cell regeneration from other cell types in the body.
