Insulin‐Producing Cells Derived from Rat Bone Marrow and Their Autologous Transplantation in the Duodenal Wall for Treating Diabetes

Abstract

Islet cell transplantation is one of the most promising therapies for diabetes mellitus (DM). However, the limited availability of purified islets for transplantation and the risk of immunological rejection severely limit its use. In vitro transdifferentiation of autologous bone marrow-derived mesenchymal stem cells (BMSCs) into insulin-producing cells (IPCs) could provide an abundant source of cells for this procedure and avoid immunological rejection. Here, we isolated and characterized BMSCs and induced their in vitro differentiation into IPCs. Reverse-transcription polymerase chain reaction analysis revealed that these IPCs could express Ins1, Ins2, glucagon, glucose transporter 2, and pancreatic duodenal homeobox-1. Insulin production by the IPCs was confirmed by immunocytochemistry and Western blot analysis. On this basis, donor rats supplying BMSCs were made diabetic by a single intraperitoneal injection of streptozotocin. The IPCs were then autologously transplanted into the duodenal submucosa of diabetic rats. Grafted cells could be visualized in sections after 2, 4, and 8 weeks by immunohistochemical staining for insulin. Furthermore, in the IPC-implanted group, hyperglycemia was normalized, compared with a persistent increase in glucose levels in the diabetic group and intraperitoneal glucose tolerance test-induced responses were observed in the IPC-implanted group. These results on autologous transplantation of IPCs derived from BMSCs into the duodenal wall could offer a novel potential therapeutical protocol for DM. Anat Rec, 292:728-735, 2009. V V C 2009 Wiley-Liss, Inc.

Supplementation of Zinc Induces Retinoic Acid-Mediated Differentiation of Rat Bone Marrow Mesenchymal Stem Cells (Mscs) in to Insulin Producing Cells (Ipcs) in-Vitro

“…The cells were positive for CD 44 and negative for CD 45 surface antigens as established already. 15,16 Hence they are unlikely to be hematopoietic stem cells and should be able to generate insulin producing cells. 8,9 Induction of retinoic acid was successful as the cell morphology changed with time.…”

“…Rat MSCs are known to be CD 44(+) and CD 45(-) 15,16 . Rat specific CD 44 and CD 45 antibodies were purchased from Biorad, USA and used following the manufacturer's recommendations.…”

Fibroblasts have plasticity and potential utility for cell therapy

“…During the first 4 days of induction culture, 10 ng/ml EGF was added. To induce conversion to insulin-producing cells, the fibroblasts were exposed to the culture conditions described for bone marrow-derived mesenchymal stem cells (MSCs) [13], with some modifications. In brief, fibroblasts were seeded at 2.0 9 10 5 per 35-mm glassbottom dish.…”

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

“…MSCs were isolated from many organs and tissues, such as bone marrow, fat tissue, umbilical cord blood, pancreas etc. (Hisanaga et al 2008;Sun et al 2007;Zhang et al 2009b). Mesenchymal stem cells are a heterogeneous population of cells capable to multidirectional differentiation (Ding et al 2011).…”