Clin Sci (Lond). 2017 Nov 3. pii: CS20171251. doi: 10.1042/CS20171251. [Epub ahead of print]

Mesenchymal stromal cells improve human islet function through released products and extracellular matrix.

Arzouni AA¹, Vargas-Seymour A¹, Rackham CL¹, Dhadda P¹, Huang GC¹, Choudhary P¹, Nardi N², King AJF¹, Jones PM³.

Abstract

Aims: The aims of the current study were (i) to determine whether the reported beneficial effects of mesenchymal stromal cells (MSCs) on mouse islet function extend to clinically relevant human tissues (islets and MSCs), enabling translation into improved protocols for clinical human islet transplantation; and (ii) to identify possible mechanisms through which human MSCs influence human islet function. Materials and methods: Human islets were co-cultured with human adipose tissue-derived MSCs (hASCs) or pretreated with its products - extracellular matrix (ECM) and annexin A1 (ANXA1). Mouse islets were pretreated with mouse MSC-derived ECM. Islet insulin secretory function was assessed in vitro by radioimmunoassay. Quantitative RT-PCR was used to screen human adipMSCs for potential ligands of human islet G-protein-coupled receptors. Results: We show that co-culture with hASCs improves human islet secretory function in vitro, as measured by glucose-stimulated insulin secretion, confirming previous reports using rodent tissues. Furthermore, we demonstrate that these beneficial effects on islet function can be partly attributed to theMSC-derived products ECM and ANXA1. Conclusions: Our results suggest that hASCs have the potential to improve the quality of human islets isolated for transplantation therapy of Type 1 diabetes. Furthermore, it may be possible to achieve improvements in human islet quality in a cell-free culture system by using the MSC-derived products ANXA1 and ECM.