Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges

Bruni, Anthony; Gala-López, Boris; Pepper, Andrew R.; Abualhassan, Nasser; Shapiro, AM James

doi:10.2147/dmso.s50789

Cited by 106 publications

(58 citation statements)

References 113 publications

(139 reference statements)

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“…Islet transplantation has been demonstrated to be the most promising approach to elucidating a cure for type 1 diabetics and it may also be a direct way to verify the in vivo activity of isolated islets (30). The intraperitoneal cavity has been shown to be one of best transplantation sites, where nutrition and oxygen are abundant (31). Blood glucose levels exhibited the same trend for all the protocols, and xenograft islets were able to control the blood glucose levels of diabetic mice following transplantation.…”

Section: Discussionmentioning

confidence: 99%

Facile mechanical shaking method is an improved isolation approach for islet preparation and transplantation

Yin

Chen

et al. 2016

Experimental and Therapeutic Medicine

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Successful islet isolation is crucial for islet transplantation and cell treatment for type 1 diabetes. Current isolation methods are able to obtain 500–1,000 islets per rat, which results in a waste of ≥50% of total islets. In the present study, a facile mechanical shaking method for improving islet yield (up to 1,500 per rat) was developed and summarized, which was demonstrated to be more effective than the existing well-established stationary method. The present results showed that isolated islets have a maximum yield of 1,326±152 when shaking for 15 min for the fully-cannulated pancreas. For both fully-cannulated and half-cannulated pancreas in the presence of rat DNAse inhibitor, the optimal shaking time was amended to 20 min with a further increased yield of 1,344±134 and 1,286±124 islets, respectively. Furthermore, the majority of the isolated islets were morphologically intact with a well-defined surface and almost no central necrotic zone, which suggested that the condition of islets obtained via the mechanical shaking method was consistent with the stationary method. Islet size distribution was also calculated and it was demonstrated that islets from the stationary method exhibited the same size distribution as the non-cannulated group, which had more larger islets than the fully-cannulated and half-cannulated groups isolated via the shaking method. In addition, the results of glucose challenge showed that the refraction index of each group was >2.5, which indicated the well-preserved function of isolated islets. Furthermore, the transplanted islets exhibited a therapeutic effect after 1 day of transplantation; however, they failed to control blood glucose levels after ~7 days of transplantation. In conclusion, these results demonstrated that the facile mechanical shaking method may markedly improve the yield of rat islet isolation, and in vitro and in vivo investigation demonstrated the well-preserved function of isolated islets in the control of blood glucose. Therefore, the facile mechanical shaking method may be an alternative improved procedure to obtain higher islet yield for islet preparation and transplantation in the treatment of type 1 diabetes.

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Section: Discussionmentioning

confidence: 99%

Facile mechanical shaking method is an improved isolation approach for islet preparation and transplantation

Yin

Chen

et al. 2016

Experimental and Therapeutic Medicine

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“…PEC-Direct™ is a macrodevice designed to allow direct vascularization of specific pancreatic progenitor cells (referred as PEC-01™), guaranteeing their maturation and in-vivo differentiation into insulin-producing cells ( 41 , 42 ).…”

Section: Encapsulation Technologymentioning

confidence: 99%

Regenerative Medicine and Diabetes: Targeting the Extracellular Matrix Beyond the Stem Cell Approach and Encapsulation Technology

et al. 2018

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According to the Juvenile Diabetes Research Foundation (JDRF), almost 1. 25 million people in the United States (US) have type 1 diabetes, which makes them dependent on insulin injections. Nationwide, type 2 diabetes rates have nearly doubled in the past 20 years resulting in more than 29 million American adults with diabetes and another 86 million in a pre-diabetic state. The International Diabetes Ferderation (IDF) has estimated that there will be almost 650 million adult diabetic patients worldwide at the end of the next 20 years (excluding patients over the age of 80). At this time, pancreas transplantation is the only available cure for selected patients, but it is offered only to a small percentage of them due to organ shortage and the risks linked to immunosuppressive regimes. Currently, exogenous insulin therapy is still considered to be the gold standard when managing diabetes, though stem cell biology is recognized as one of the most promising strategies for restoring endocrine pancreatic function. However, many issues remain to be solved, and there are currently no recognized treatments for diabetes based on stem cells. In addition to stem cell resesarch, several β-cell substitutive therapies have been explored in the recent era, including the use of acellular extracellular matrix scaffolding as a template for cellular seeding, thus providing an empty template to be repopulated with β-cells. Although this bioengineering approach still has to overcome important hurdles in regards to clinical application (including the origin of insulin producing cells as well as immune-related limitations), it could theoretically provide an inexhaustible source of bio-engineered pancreases.

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“…This method is limited by the scarcity of donors and the inherent graft decay, with only 44% of the recipients being insulin-independent 3 years after transplantation 7 . Consequently, finding a more accessible source of β-cells is mandatory for the development of regenerative therapies to treat diabetes.…”

Section: Choosing a β-Cell Reconstitution Strategy: Replacement Vs Rmentioning

confidence: 99%

Regeneration of pancreatic insulin-producing cells by in situ adaptive cell conversion

Chera

Herrera

2016

Current Opinion in Genetics & Development

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The impaired ability to produce or respond to insulin, a hormone synthetized by the pancreatic β-cells, leads to diabetes. There is an excruciating need of finding new approaches to protect or restore these cells once they are lost. Replacement and ex vivo directed reprogramming methods have an undeniable therapeutic potential, yet they exhibit crucial flaws. The in vivo conversion of adult cells to functional insulin-producing cells is a promising alternative for regenerative treatments in diabetes. The stunning natural transdifferentiation potential of the adult endocrine pancreas was recently uncovered. Modulating molecular targets involved in β-cell fate maintenance or in general differentiation mechanisms can further potentiate this intrinsic cell plasticity, which leads to insulin production reconstitution.

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Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges

Cited by 106 publications

References 113 publications

Facile mechanical shaking method is an improved isolation approach for islet preparation and transplantation

Facile mechanical shaking method is an improved isolation approach for islet preparation and transplantation

Regenerative Medicine and Diabetes: Targeting the Extracellular Matrix Beyond the Stem Cell Approach and Encapsulation Technology

Regeneration of pancreatic insulin-producing cells by in situ adaptive cell conversion

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