Assessment of Immune Isolation of Allogeneic Mouse Pancreatic Progenitor Cells by a Macroencapsulation Device

Abstract

Background Embryonic-stem-cell (ESC)-derived islets hold the promise of providing a renewable source of tissue for the treatment of insulin-dependent diabetes. Encapsulation may allow ESC-derived islets to be transplanted without immunosuppression, thus enabling wider application of this therapy. Methods In this study, we investigated the immunogenicity of mouse pancreatic progenitor cells and efficacy of a new macroencapsulation device in protecting these cells against alloimmune and autoimmune responses in mouse models. Results Mouse pancreatic progenitor cells activated the indirect but not the direct pathway of alloimmune response and were promptly rejected in immune competent hosts. The new macroencapsulation device abolished T cell activation induced by allogeneic splenocytes and protected allogeneic MIN6 β cells and pancreatic progenitors from rejection even in pre-sensitized recipients. In addition, the device was effective in protecting MIN6 cells in spontaneously diabetic non-obese diabetic recipients against both alloimmune and recurring autoimmune responses. Conclusion Our results demonstrate that macroencapsulation can effectively prevent immune sensing and rejection of allogeneic pancreatic progenitor cells in fully sensitized and autoimmune hosts.

A nanofibrous encapsulation device for safe delivery of insulin-producing cells to treat type 1 diabetes

“…Different types of immune cells surrounded the device, including CD4 + T cells, B cells, macrophages, dendritic cells, and neutrophils; however, very few CD8 + T cells were present even in xenografts. This may be important because CD8 + T cells are known to be recruited in nonimmunoprotected  cell transplantation and can directly destroy allogeneic islets by releasing granzyme B and perforins (28,57). Moreover, antibody analysis showed that there were elevated IgG and IgM concentrations and existence of alloantibodies in the serum of recipient mice and that a stronger antibody response was found in the mice with devices encapsulating xenogeneic islets than in those with devices encapsulating syngeneic or allogeneic islets.…”

Cell Transplantation Combined with Recombinant Collagen Peptides for the Treatment of Fabry Disease

“…Two or more digit higher of enzyme release with M6P by gene-modified cells could be feasible, and work to address the number of cells and wells could be applicable to clinical fields. In addition, the encapsulation of cells via either microencapsulation or macroencapsulation to support the release of biological materials such as insulin has been intensively investigated 32,33 , but the strategy has not reached the clinical arena as a standard therapy mainly due to cellular durability. There have been no reports of the use of these technologies to treat lysosomal diseases.…”

Stem cells in the treatment of diabetes mellitus — Focus on mesenchymal stem cells

“…In addition, once maturated into insulin producing β-cells, graft cells will be attacked by persistent autoreactive T cells in patients with T1DM. Several studies have demonstrated that macroencapsulation protects embedded cells by isolation from immune responses and thereby avoids rejection and the need for immunosuppression [27,28]. Furthermore, macroencapsulation prevents escape of embedded cells into the body.…”