Reduction of Marginal Mass Required for Successful Islet Transplantation in a Diabetic Rat Model Using Adipose Tissue–Derived Mesenchymal Stromal Cells Publisher Pubmed



Navaeinigjeh M^{1, 2, 7} ; Moloudizargari M³ ; Baeeri M² ; Gholami M² ; Lotfibakhshaiesh N^{1, 7} ; Soleimani M⁴ ; Vasheghanifarahani E⁵ ; Ai J^{1, 7} ; Abdollahi M^{2, 6}
Source: Cytotherapy Published:2018

Abstract

Background aims: Adipose tissue–derived mesenchymal stromal cells (AT-MSCs), widely known as multipotent progenitors, release several cytokines that support cell survival and repair. There are in vitro and in vivo studies reporting the regenerative role of AT-MSCs possibly mediated by their protective effects on functional islet cells as well as their capacity to differentiate into insulin-producing cells (IPCs). Methods: On such a basis, our goal in the present study was to use three different models including direct and indirect co-cultures and islet-derived conditioned medium (CM) to differentiate AT-MSCs into IPCs and to illuminate the molecular mechanisms of the beneficial impact of AT-MSCs on pancreatic islet functionality. Furthermore, we combined in vitro co-culture of islets and AT-MSCs with in vivo assessment of islet graft function to assess whether co-transplantation of islets with AT-MSCs can reduce marginal mass required for successful islet transplantation and prolong graft function in a diabetic rat model. Results: Our findings demonstrated that AT-MSCs are suitable for creating a microenvironment favorable for the repair and longevity of the pancreas β cells through the improvement of islet survival and maintenance of cell morphology and insulin secretion due to their potent properties in differentiation. Most importantly, hybrid transplantation of islets with AT-MSCs significantly promoted survival, engraftment and insulin-producing function of the graft and reduced the islet mass required for reversal of diabetes. Conclusions: This strategy might be of therapeutic potential solving the problem of donor islet material loss that currently limits the application of allogeneic islet transplantation as a more widespread therapy for type 1 diabetes. © 2018 Elsevier Ltd