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Directed Differentiation (directed + differentiation)

Distribution by Scientific Domains
Medical Sciences75%

Selected Abstracts

Progenitor cells in the adult pancreas

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2004
Andrew M. Holland
Abstract The ,-cell mass in the adult pancreas possesses the ability to undergo limited regeneration following injury. Identifying the progenitor cells involved in this process and understanding the mechanisms leading to their maturation will open new avenues for the treatment of type 1 diabetes. However, despite steady advances in determining the molecular basis of early pancreatic development, the identification of pancreatic stem cells or ,-cell progenitors and the molecular mechanisms underlying ,-cell regeneration remain unclear. Recent advances in the directed differentiation of embryonic and adult stem cells has heightened interest in the possible application of stem cell therapy in the treatment of type 1 diabetes. Drawing on the expanding knowledge of pancreas development, ,-cell regeneration and stem cell research, this review focuses on progenitor cells in the adult pancreas as a potential source of ,-cells. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Electrical and neurotransmitter activity of mature neurons derived from mouse embryonic stem cells by Sox-1 lineage selection and directed differentiation

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2004
R. J. Lang
Abstract Sx1TV2/16C is a mouse embryonic stem (ES) cell line in which one copy of the Sox1 gene, an early neuroectodermal marker, has been targeted with a neomycin (G418) selection cassette. A combination of directed differentiation with retinoic acid and G418 selection results in an enriched neural stem cell population that can be further differentiated into neurons. After 6,7 days post-plating (D6,7PP) most neurons readily fired tetrodotoxin (TTX)-sensitive action potentials due to the expression of TTX-sensitive Na+ and tetraethylammonium (TEA)-sensitive K+ channels. Neurons reached their maximal cell capacitance after D6,7PP; however, ion channel expression continued until at least D21PP. The percentage of cells receiving spontaneous synaptic currents (s.s.c.) increased with days in culture until 100% of cells received a synaptic input by D20PP. Spontaneous synaptic currents were reduced in amplitude and frequency by TTX, or upon exposure to a Ca2+ -free, 2.5 mm Mg2+ saline. S.s.c. of rapid decay time constants were preferentially blocked by the nonNMDA glutamatergic receptor antagonists CNQX or NBQX. Ca2+ levels within ES cell-derived neurons increased in response to glutamate receptor agonists l -glutamate, AMPA, N -methyl- d -aspartate (NMDA) and kainic acid and to acetylcholine, ATP and dopamine. ES cell-derived neurons also generated cationic and Cl, -selective currents in response to NMDA and glycine or GABA, respectively. It was concluded that ES-derived neurons fire action potentials, receive excitatory and inhibitory synaptic input and respond to various neurotransmitters in a manner akin to primary central neurons. [source]

Toward a cell-based cure for diabetes: advances in production and transplant of beta cells

MOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 4 2008
Kathryn C. Claiborn
Abstract Type 1 diabetes results from autoimmune destruction of the insulin-producing beta cells of the pancreatic islets of Langerhans. Although developments in exogenous insulin therapy have greatly improved clinical outcomes in patients with diabetes, the ability of the pancreatic beta cell to exquisitely regulate the delivery of insulin and maintain normal levels of blood glucose is still far superior to what can be achieved by external delivery of insulin. As a result, the majority of patients with type 1 diabetes still experience the complications of chronic hyperglycemia or serious and potentially life-threatening hypoglycemia. The shortcomings of medical therapy have driven research toward more direct approaches of beta cell replacement. Indeed, the specificity of beta cell loss in type 1 diabetes makes this disease a particularly attractive candidate for cell-based therapies. In order for significant progress to be made, however, a thorough understanding of beta cell biology and more broadly islet biology is necessary. This review addresses recent advances in developmental biology that have expanded our understanding of islet cell differentiation, assesses the promise and limitations of islet transplantation, and discusses the future of alternative sources of beta cells, including directed differentiation of stem cells, replication of adult beta cells, and transdifferentiation of nonislet cells to a beta cell fate. Mt Sinai J Med 75:362,371, 2008. © 2008 Mount Sinai School of Medicine [source]

Stem cells and diabetes treatment,

APMIS, Issue 11-12 2005
OLE DRAGSBÆK MADSEN
Diabetes mellitus types 1 and 2 are characterized by absolute versus relative lack of insulin-producing , cells, respectively. Reconstitution of a functional ,-cell mass by cell therapy , using organ donor islets of Langerhans , has been demonstrated to restore euglycaemia in the absence of insulin treatment. This remarkable achievement has stimulated the search for appropriate stem cell sources from which adequate expansion and maturation of therapeutic , cells can be achieved. This recent activity is reviewed and presented with particular focus on directed differentiation from pluripotent embryonic stem cells (versus other stem/progenitor cell sources) based on knowledge from pancreatic ,-cell development and the parallel approach to controlling endogenous ,-cell neogenesis. [source]