Chitosan-assisted differentiation of porcine adipose tissue-derived stem cells into glucose-responsive insulin-secreting clusters

Abstract

The unique advantage of easy access and abundance make the adipose-derived stem cells (ADSCs) a promising system of multipotent cells for transplantation and regenerative medicine. Among the available sources, porcine ADSCs (pADSCs) deserve especial attention due to the close resemblance of human and porcine physiology, as well as for the upcoming availability of humanized porcine models. Here, we report on the isolation and conversion of pADSCs into glucose-responsive insulin-secreting cells. We used the stromal-vascular fraction of the dorsal subcutaneous adipose from 9-day-old male piglets to isolate pADSCs, and subjected the cells to an induction scheme for differentiation on chitosan-coated plates. This one-step procedure promoted differentiation of pADSCs into pancreatic islet-like clusters (PILC) that are characterized by the expression of a repertoire of pancreatic proteins, including pancreatic and duodenal homeobox (Pdx-1), insulin gene enhancer protein (ISL-1) and insulin. Upon glucose challenge, these PILC secreted high amounts of insulin in a dose-dependent manner. Our data also suggest that chitosan plays roles not only to enhance the differentiation potential of pADSCs, but also to increase the glucose responsiveness of PILCs. Our novel approach is, therefore, of great potential for transplantation-based amelioration of type 1 diabetes.

Effect of Stem Cells and Gene Transfected Stem Cells Therapy on the Pancreas of Experimentally Induced Type 1 Diabetes

“…In agreement, Liu et al (37) mentioned that in case of treatment with MSCs, β-cells insulin immunoreactions were obviously improved and referred the previous findings to the multipotency of MSCs and their abililty to transdifferentiate into insulin producing β cells.…”

Properties of porcine adipose-derived stem cells and their applications in preclinical models

“…Currently, it has been reported that pASCs can transdifferentiate into hepatocytes, 17,24 neurons, 11,25 and pancreatic islet-like clusters. 26 Using lentivirals carrying reprogramming factors, pASCs have also been reprogrammed into induced pluripotent stem cells (iPSCs). 19,27 Song et al also described that pASCs could also differentiate into oocyte-like cells.…”

Engineering immunomodulatory biomaterials for type 1 diabetes

“…For example, 3D printed cell-laden hydrogel scaffolds could not only provide precise spatial distribution of the transplanted cells 241 , but also allow co-printing with immune regulatory cells or agents 242 , enabling highly localized immunregulation. Biomaterials and microprinting technologies can further assist in improving stem cellderived beta cell differentiation and pseudo islet formation 243,244 . The transition from cadaveric islet sources, with unpredictable HLA profiles, to a defined stem cell-derived beta cell source, with the capacity to generate HLA-typed cell banks, provides the opportunity to decrease allogeneic beta cell rejection by tailoring the donor MHC to the patient.…”