Change in Viability and Function of Pancreatic Islets after Coculture with Mesenchymal Stromal Cells: A Systemic Review and Meta-Analysis

Abstract

Background. There is no clear consensus on the effect of coculture of islets with mesenchymal stem cells (MSCs) on islet function and viability. Methods. We conducted a meta-analysis of relevant studies to evaluate the effect of coculture of islets with MSCs on the function and viability of islets, both in vitro and in vivo. We searched PubMed, Embase, and Web of Science databases for all relevant studies that compared the effect of coculture of islets with MSCs on the function and viability of islets (language of publication: English; reference period: January 2000-May 2019). Data pertaining to islet function and viability, concentrations of some cytokines, and in vivo experimental outcomes were extracted and compared. Results. Twenty-four articles were included in the meta-analysis. In comparison to islets cultured alone, coculture of islets with MSCs was associated with a significantly higher islet viability [weighted mean difference (WMD),-15.59;-22.34 to-8.83; P<0.00001], insulin level (WMD,-5.74;-9.29 to-2.19; P=0.002), insulin secretion index (WMD,-2.45;-3.70 to-1.21; P=0.0001), and higher concentrations of interleukin-6 (WMD,-1225.66;-2044.47 to-406.86; P=0.003) and vascular endothelial growth factor (WMD,-1.19;-2.25 to-0.14; P=0.03). Direct coculture of islets and MSCs significantly increased islet viability (WMD,-19.82;-26.56 to-13.07; P<0.00001). In the in vivo experiments, coculture of islets with MSCs induced lower fasting blood glucose level (on postoperative days 21 and 28, WMD, 102.60; 27.14 to 178.05; P=0.008 and WMD, 121.19; 49.56 to 192.82; P=0.0009) and better glucose tolerance (blood glucose at 30 minutes after intraperitoneal injection of glucose, WMD, 85.92; 5.33 to 166.51; P=0.04). Conclusion. Coculture of islets with MSCs improves insulin secretory function of islets and enhances islet viability. Direct coculture of two cells significantly increased islet viability. MSC-based strategy may be beneficial for clinical islet transplantation for type 1 diabetes in the future.