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.
Highlights
Type 1 diabetes mellitus (T1DM) is a disease of impaired glucose homeostasis resulting from autoimmune destruction of pancreatic islet cells accounting for 5–10% of diabetes mellitus worldwide [1]
With the assistance of a chitosan matrix, adipose-derived stem cells (ADSCs) derived from dorsal subcutaneous adipose tissues of piglets can be differentiated into high insulin-secreting Pancreatic Islet-Like Clusters (PILC) that are responsive to a glucose challenge
Functional characterization of multipotency confirms that our porcine ADSCs (pADSCs) can be differentiated into adipocytes, osteocytes and chondrocytes (Fig 1B), as stained by specific dyes
Summary
Type 1 diabetes mellitus (T1DM) is a disease of impaired glucose homeostasis resulting from autoimmune destruction of pancreatic islet cells accounting for 5–10% of diabetes mellitus worldwide [1]. Approaches using tissue transplantation with human or animal pancreatic islets [3,4,5,6] and cell therapy [7] with various sources of β-cell-like cells have emerged as alternatives. These cells can be derived from embryonic [8,9] or adult-tissue stem cells obtained from liver [10], umbilical cord blood [11,12], skin fibroblasts [13], placenta [14], bone marrow [15], pancreatic progenitor cells [16] and periosteum [17]
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