Use of Mesenchymal Stem Cell-Conditioned Medium to Activate Islets in Preservation Solution

Abstract

Pancreatic islet transplantation has received widespread attention as a promising treatment for type 1 diabetes. However, islets for transplantation are subject to damage from a number of sources, including ischemic injury during removal and delivery of the donor pancreas, enzymatic digestion during islet isolation, and reperfusion injury after transplantation in the recipient. Here we found that protein fractions secreted by mesenchymal stem cells (MSCs) were capable of activating preserved islets. A conditioned medium from the supernatant obtained by culturing adipose tissue MSCs (derived from wild-type Lewis rats) was prepared for 2 days in serum-free medium. Luc-Tg rat islets to which an organ preservation solution was added were then incubated at 4°C with fractions of various molecular weights prepared from the conditioned medium. Under the treatment with some of the fractions, by 4 days the relative luminescence intensities (representative of the ATP levels of the cold-preserved islets) had increased to over 150% of their initial values. Our novel system may be able to restore isolated islets to the condition they were in before transport, culture, and transplantation.

Distinct Factors Secreted by Adipose Stromal Cells Protect the Endothelium From Barrier Dysfunction and Apoptosis

“…As one can expect, the MW of active fraction depends on the nature of activity for which it is tested for. For example, the ability to preserve pancreatic islets was assigned to 10-30 and > 50 kDa fractions of ASC-CM (Kasahara et al, 2013). The ability to promote macrophage shift to anti-inflammatory phenotype was assigned to < 3 and 50-100 kDa fractions of CM (Ylostalo et al, 2012).…”

Role of Mesenchymal Stem/Stromal Cells in Modulating Ischemia/Reperfusion Injury: Current State of the Art and Future Perspectives

“…Across the last decade, it has been shown that the treatment with MSCs was able to induce islet regeneration, increase islet function, and inhibit immune system reactions in various animal models of T1D [ 131 ]. Kasahara et al found that AdMSCs-CM administered through a preservation solution was able to restore rat islets to the condition they were in before transport, culture, and transplantation [ 132 ]. Similar results were found by Teratani et al, in which the MSC-derived CM added to the UW solution was able to preserve porcine islets during both transportation and cultures [ 133 ].…”

Therapeutic Potential of Mesenchymal Stem Cell‐Derived Conditioned Medium for Diabetes Mellitus and Related Complications

“…[ 151 ] Implantation difficulties can occur for several reasons, including ischemic injury during removal and delivery of the donor pancreas, enzymatic digestion during islet isolation, and reperfusion injury in the recipient after transplantation. [ 152 ] In this regard, the proliferative, angiogenic, and anti‐apoptotic properties of MSCs can increase survival, and cell formation after transplantation, and their immunosuppressive properties may reduce the likelihood of rejection. It was indicated in a study that protein fractions secreted by MSCs could activate preserved islets.…”

“…Using these factors, it could be possible to return islets to their pre‐culture conditions. [ 152 ] Hypoxia is one of the crucial factors reducing the survival of islet cells after transplantation. The angiogenic and protective effects of MSCs can be exploited to increase their chances of survival in the hypoxic microenvironment in which they are transplanted.…”