Preculturing Islets With Adipose-Derived Mesenchymal Stromal Cells Is an Effective Strategy for Improving Transplantation Efficiency at the Clinically Preferred Intraportal Site.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

We have recently shown that preculturing islets with kidney-derived mesenchymal stromal cells (MSCs) improves transplantation outcome in streptozotocin-diabetic mice implanted with a minimal mass of islets beneath the kidney capsule. In the present study, we have extended our previous observations to investigate whether preculturing islets with MSCs can also be used to enhance islet function at the clinically used intraportal site. We have used MSCs derived from adipose tissue, which are more readily accessible than alternative sources in human subjects and can be expanded to clinically efficacious numbers, to preculture islets throughout this study. The in vivo efficacy of grafts consisting of islets precultured alone or with MSCs was tested using a syngeneic streptozotocin-diabetic minimal islet mass model at the clinically relevant intraportal site. Blood glucose concentrations were monitored for 1 month. The vascularization of islets precultured alone or with MSCs was investigated both in vitro and in vivo, using immunohistochemistry. Islet insulin content was measured by radioimmunoassay. The effect of preculturing islets with MSCs on islet function in vitro was investigated using static incubation assays. There was no beneficial angiogenic influence of MSC preculture, as demonstrated by the comparable vascularization of islets precultured alone or with MSCs, both in vitro

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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