Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells

Abstract

Ductal structures of the adult pancreas contain stem cells that differentiate into islets of Langerhans. Here, we grew pancreatic ductal epithelial cells isolated from prediabetic adult non-obese diabetic mice in long-term cultures, where they were induced to produce functioning islets containing alpha, beta and delta cells. These in vitro-generated islets showed temporal changes in mRNA transcripts for islet cell-associated differentiation markers, responded in vitro to glucose challenge, and reversed insulin-dependent diabetes after being implanted into diabetic non-obese diabetic mice. The ability to control growth and differentiation of islet stem cells provides an abundant islet source for beta-cell reconstitution in type I diabetes.

Mechanisms of action of glucagon-like peptide 1 in the pancreas

“…In 2000 Peck and colleagues showed that it was possible to cultivate and expand a cell with neuroendocrine-type morphology from the mouse pancreas that could then give rise to isletlike clusters expressing insulin and glucagon (Ramiya et al, 2000). When implanted into the subcapsular region of the kidney of diabetic female NOD/Uf mice, (although they had slightly elevated blood glucose levels relative to controls) they survived insulin-free for up to 55 days.…”

Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors

“…Stem cells capable of reconstituting the tissues in which they reside include myosatellite cells in skeletal muscle (Grounds, 1999), chondroblasts in the perichondrium surrounding cartilage (Yotsuyanagi et al, 1999), oval cells in the liver (Gordon et al, 2000), preductal stem cells in the pancreas (Bonner-Wier et al, 2000;Ramiya et al, 2000), basal stem cells of epithelial tissues (Slack, 2000), and neuronal stem cells in the brain (Gage, 2000). By contrast, other studies have shown that stem cells residing in one tissue can differentiate into cell types of another tissue.…”

Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells

“…The endocrine compartment consists of the islets of Langerhans, which contain clusters of studies have shown the existence of pancreatic stem cells [2,3,4,5], these cells have not yet been isolated from the pancreas in a pure form.…”