Multipotent Mesenchymal Stromal Cells Interact and Support Islet of Langerhans Viability and Function

Abstract

Type 1 diabetes (T1D) is a widespread disease, affecting approximately 41.5 million people worldwide. It is generally treated with exogenous insulin, maintaining physiological blood glucose levels but also leading to long-term therapeutic complications. Pancreatic islet cell transplantation offers a potential alternative treatment to insulin injections. Shortage of human organ donors has raised the interest for porcine islet xenotransplantation. Neonatal porcine islets are highly available, can proliferate and mature in vitro as well as after transplantation in vivo. Despite promising preclinical results, delayed insulin secretion caused by immaturity and immunogenicity of the neonatal porcine islets remains a challenge for their clinical application. Multipotent mesenchymal stromal cells (MSCs) are known to have pro-angiogenic, anti-inflammatory and immunomodulatory effects. The current state of research emphasizes the great potential of co-culture and co-transplantation of islet cells with MSCs. Studies have shown enhanced islet proliferation and maturation, insulin secretion and graft survival, resulting in an improved graft outcome. This review summarizes the immunomodulatory and anti-inflammatory properties of MSC in the context of islet transplantation.

Keywords: MSC; cell encapsulation; diabetes; neonatal porcine islets; xenotransplantion.

Figure 1

In vitro differentiation of isolated porcine pancreatic islet cell clusters: Panel (A) shows cell clusters containing insulin-positive beta cells (green) and CK7-positive pancreatic exocrine tissue (red) at 3 days after isolation. Panel (B) shows pancreatic islet cell clusters 7 days after culture in neonatal pig islet differentiation media (scale bar represents 250 μm).