Utility of co-transplanting mesenchymal stem cells in islet transplantation.

Naoaki Sakata, Gumpei Yoshimatsu, Shinichi Egawa, Michiaki Unno, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.
World Journal of Gastroenterology (Impact Factor: 2.43). 12/2011; 17(47):5150-5. DOI: 10.3748/wjg.v17.i47.5150
Source: PubMed

ABSTRACT Islet transplantation is characterized by the transplantation of isolated islets from donor pancreata into a diabetic recipient. Although it is a viable choice in the treatment of insulin dependent diabetes mellitus, most patients (approximately 90%) require insulin five years after transplantation. Recently, the co-transplantation of mesenchymal stem cells (MSCs) and islets in animal studies has revealed the effectiveness of MSCs co-transplantation for improving islet function. The mechanisms underlying the beneficial impact of MSCs include immunomodulation and the promotion of angiogenesis. In this review, we discuss MSCs and how they support improved graft survival and function.

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    ABSTRACT: Biofunctionalized polyethylene glycol maleimide (PEG–MAL) hydrogels were engineered as a platform to deliver pancreatic islets to the small bowel mesentery and promote graft vascularization. VEGF, a potent stimulator of angiogenesis, was incorporated into the hydrogel to be released in an on-demand manner through enzymatic degradation. PEG–MAL hydrogel enabled extended in vivo release of VEGF. Isolated rat islets encapsulated in PEG–MAL hydrogels remained viable in culture and secreted insulin. Islets encapsulated in PEG–MAL matrix and transplanted to the small bowel mesentery of healthy rats grafted to the host tissue and revascularized by 4 weeks. Addition of VEGF release to the PEG–MAL matrix greatly augmented the vascularization response. These results establish PEG–MAL engineered matrices as a vascular-inductive cell delivery vehicle and warrant their further investigation as islet transplantation vehicles in diabetic animal models.
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    ABSTRACT: Generation of surrogate β-cells is the need of the day to compensate the short supply of islets for transplantation to diabetic patients requiring daily shots of insulin. Over the years several sources of stem cells have been claimed to cater to the need of insulin producing cells. These include human embryonic stem cells, induced pluripotent stem cells, human perinatal tissues such as amnion, placenta, umbilical cord and postnatal tissues involving adipose tissue, one marrow, blood monocytes, cord blood, dental pulp, endometrium, liver, labia minora dermis-derived fibroblasts and pancreas. Despite the availability of such heterogonous sources, there is no substantial breakthrough in selecting and implementing an ideal source for generating large number of stable insulin producing cells. Although the progress in derivation of β-cell like cells from embryonic stem cells has taken a greater leap, their application is limited due to controversy surrounding the destruction of human embryo and immune rejection. Since multipotent mesenchymal stromal cells are free of ethical and immunological complications, they could provide unprecedented opportunity as starting material to derive insulin secreting cells. The main focus of this review is to discuss the merits and demerits of MSCs obtained from human peri- and post-natal tissue sources to yield abundant glucose responsive insulin producing cells as ideal candidates for prospective stem cell therapy to treat diabetes.
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