Diabetes Mellitus-Cell Transplantation and Gene Therapy Approaches.

Halvorsen, Tanya; Levine, Fred

doi:10.2174/1566524013363951

Cited by 12 publications

(5 citation statements)

References 93 publications

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“…Attempts to expand β‐cells In vitro have been difficult. Typically purified islets divide slowly in culture, lose insulin expression and are gradually overtaken by insulin negative cells [152–155]. Recent data from three groups, however, suggested cultured human islets can dedifferentiate and expand, via an epithelialmesenchymal transition, and then be directed to redifferentiate back toward a β‐cell phenotype [9, 52, 156].…”

Section: β‐Cell Replication Increases During Pregnancymentioning

confidence: 99%

Slow and steady is the key to β‐cell replication

Brennand

Melton

2009

J Cellular Molecular Medi

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The β-cells of the pancreas are responsible for insulin production and their destruction results in type I diabetes. β-cell maintenance, growth and regenerative repair is thought to occur predominately, if not exclusively, through the replication of existing β-cells, not via an adult stem cell. It was recently found that all β-cells contribute equally to islet growth and maintenance. The fact that all β-cells replicate homogeneously makes it possible to set up straightforward screens for factors that increase β-cell replication either In vitro or in vivo. It is possible that a circulating factor may be capable of increasing β-cell replication or that intrinsic cell cycle regulators may affect β-cell growth. An improved understanding of the in vivo maintenance and growth of β-cells will facilitate efforts to expand β-cells In vitro and may lead to new treatments for diabetes.

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Section: β‐Cell Replication Increases During Pregnancymentioning

confidence: 99%

Slow and steady is the key to β‐cell replication

Brennand

Melton

2009

J Cellular Molecular Medi

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“…Various endeavors to solve this challenge have been made through stimulating the endogenous regeneration of islets and through transplantation of donor islets or in vitro-differentiated islet-like cells. [11][12][13][14] Recent reports have described, a multipotent stem cell within the pancreas. 15 These cells have the capacity to differentiate into pancreatic islet-like structures in vitro.…”

mentioning

confidence: 99%

Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes

Muzzonigro²,

Bae³

et al. 2004

Laboratory Investigation

245

176

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Recent findings suggest that bone marrow (BM) cells have the capacity to differentiate into a variety of cell types including endocrine cells of the pancreas. We report that BM derived cells, when cultured under defined conditions, were induced to trans-differentiate into insulin-producing cells. Furthermore, these insulinproducing cells formed aggregates that, upon transplantation into mice, acquired architecture similar to islets of Langerhans. These aggregates showed endocrine gene expression for insulin (I and II), glucagon, somatostatin and pancreatic polypeptide. Immunohistochemistry also confirmed that these aggregates were positive for insulin, somatostatin, pancreatic polypeptide and C-peptide. Also, Western and ELISA analysis demonstrated expression of proinsulin and/or secretion of active insulin upon glucose challenge. Subcapsular renal transplantation of these aggregates into hyperglycemic mice lowered circulating blood glucose levels and maintained comparatively normal glucose levels for up to 90 days post-transplantation. Graft removal resulted in rapid relapse and death in experimental animals. In addition, electron microscopy revealed these aggregates had acquired ultrastructure typically associated with mature beta (b) cells. These results demonstrate that adult BM cells are capable of trans-differentiating into a pancreatic lineage in vitro and may represent a pool of cells for the treatment of diabetes mellitus.

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“…The understanding of β‐cell neogenesis regulatory signals would allow not only the possibility to enhance in vivo regeneration of islet cells, but also the possibility to exogenously replace insulin‐producing cells. Improved conditions of transplantation of pancreatic islet cells are currently investigated as a strategy of diabetes therapy (Halvorsen and Levine, 2001; Shapiro et al, 2001). Recent studies, performed on human and rat pancreatic ductal cell line (hPANC‐1 and ARIP), indicated that treatment with GLP‐1 is indeed able to promote their differentiation into insulin producing and secreting cells (Hui et al, 2001), and for this reason, these cells represent a valuable in vitro model to study β‐cell differentiation.…”

mentioning

confidence: 99%

3,5,3′‐Triiodo‐L‐thyronine enhances the differentiation of a human pancreatic duct cell line (hPANC‐1) towards a β‐cell‐Like phenotype

Misiti

Anastasi

Sciacchitano

et al. 2005

Journal Cellular Physiology

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The thyroid hormone, 3,5,3'-Triiodo-L-thyronine (T3), is essential for growth, differentiation, and regulation of metabolic functions in multicellular organisms, although the specific mechanisms of this control are still unknown. In this study, treatment of a human pancreatic duct cell line (hPANC-1) with T3 blocks cell growth by an increase of cells in G(0)/G(1) cell cycle phase and enhances morphological and functional changes as indicated by the marked increase in the synthesis of insulin and the parallel decrease of the ductal differentiation marker cytokeratin19. Expression analysis of some of the genes regulating pancreatic beta-cell differentiation revealed a time-dependent increase in insulin and glut2 mRNA levels in response to T3. As last step of the acquisition of a beta-cell-like phenotype, we present evidence that thyroid hormones are able to increase the release of insulin into the culture medium. In conclusion, our results suggest, for the first time, that thyroid hormones induce cell cycle perturbations and play an important role in the process of transdifferentiation of a human pancreatic duct line (hPANC-1) into pancreatic-beta-cell-like cells. These findings have important implications in cell-therapy based treatment of diabetes and may provide important insights in the designing of novel therapeutic agents to restore normal glycemia in subjects with diabetes.

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Diabetes Mellitus-Cell Transplantation and Gene Therapy Approaches.

Cited by 12 publications

References 93 publications

Slow and steady is the key to β‐cell replication

Slow and steady is the key to β‐cell replication

Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes

3,5,3′‐Triiodo‐L‐thyronine enhances the differentiation of a human pancreatic duct cell line (hPANC‐1) towards a β‐cell‐Like phenotype

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