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Essay: Regenerative medicine

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  • Published: 27 October 2015*
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  • Words: 715 (approx)
  • Number of pages: 3 (approx)

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Regenerative medicine represents one of the main concerns of medicine. The present study aims to investigate an alternative technique for islet transplantation by evaluating the effect of transplanting newly generated islet-like cell clusters (ILCs) from human mesenchymal stem cells of the umbilical cord (hUCMSCs) into streptozotocin (STZ) -induced diabetic rats via the tail vein or intraperitoneally as two different transplantation methods. Human UCMSCs were found to express CD90, and were negative for CD33, CD23, CD45 and HLA DR. When hUCMSCs subjected to specific differentiation factors, these cells differentiated into ILCs. These newly formed ILCs stained positive for H&E staining and expressed insulin. On transplantation via the tail vein or intraperitoneally into diabetic rats, these ILCs restored normoglycemia, indicating their functional status. Histomorphological and morphometric examination of the stained pancreatic sections revealed a significant increase in the area, and diameter of the ??-cells of pancreatic islets in the ILCs-treated groups. Thus, Transplanting ILCs generated from hUCMSCs either via the tail vein or intraperitoneally, seem to be the preferential stem cell therapy to alleviate hyperglycemia in the STZ- induced diabetic rats .
Keywords: Mesenchymal stem cell; Islet-like cell clusters; tail vein; intraperitoneal; histology; histomorphometry
Abbreviations: hUCMSCs, Human mesenchymal stem cells of umbilical cord; ILCs, Islet-like cell clusters; STZ, Streptozotocin
1. Introduction
Type 1 diabetes mellitus (DM) is an organ specific autoimmune disease, because of the destruction of the insulin secreting beta cells in the islets of Langerhans of the pancreas [1]. At the clinical onset of type 1 DM, about 80% of islets contain no insulin secreting islet cells, and the islets maybe infiltrated with mononuclear cells [2], with a predominance of macrophages and CD8+ T lymphocytes [3]. This infiltrate is, directly or indirectly, probably the major cause of the beta-cells destruction. Replacement of a diabetic patient’s islets is the only treatment of type 1 DM that achieves constant normoglycaemic state and avoids hypoglycaemic episodes [4]. However, islet transplantation has been hampered by the worldwide shortage of transplant-ready islets, immune rejection, and recurrent attacks against islets by the underlying autoimmunity [5].
Recently, there is a widespread interest in generating new insulin- producing cells in vitro from non-?? cells [6-10]. Progenitor cells from various cellular sources, including pancreatic stem cells [11,12], hepatic stem cells [13], neural progenitor cells [14], umbilical cord blood cells [15], bone marrow- derived cells [16], and embryonic stem cells [17] have previously been used in research on regeneration therapies for DM. However, both embryonic stem cells (ESCs) and fetus-derived stem cells have ethical problems which impede there application into the clinical settings. Meanwhile, bone marrow-derived cells were reported to have more limited expansion and differentiation capacities with advanced age [18]. Considering all of these limitations, postnatal stem cells may yet prove to be the most important and potentially, the useful source of stem cells.
As an excellent candidate for cell-based therapy in regenerative medicine and tissue engineering, mesenchymal stem cells (MSCs) are multipotent, and it has been demonstrated that mouse marrow MSCs cultured in high glucose for 4 months or rat marrow MSCs cultured with pancreatic extract [9,19] can differentiate into insulin-expressing cells..
Mesenchymal stem cells isolated from the Wharton’s jelly of the human umbilical cord (hUCMSCs) have been found to contain fibroblast-like cells , which are similar to MSCs in the bone marrow [20] and could be differentiated into adipogenic cells , osteogenic cells , cardiomyogenic cells , and insulin- producing cells [20,21]. They are also easily obtained and processed [22,23], compared with embryonic and other stem cells. In the present study, we first characterized undifferentiated hUCMSCs and islet-like cell clusters (ILCs) generated from the differentiation by various methods. Subsequently, we transplanted the undifferentiated hUCMSCs into the tail vein of some streptozotocin- induced diabetic rats, while other rats were transplanted with the newly formed ILCs in two various ways (via the tail vein or intraperitoneally) rather than using portal vein [24,25] or renal sub-capsular space [26] . In our study, we used the streptozotocin (STZ) which is a naturally occurring diabetogenic chemical in diabetes research , and its toxicity to the pancreatic ??- cells in mammals can induce type 1 DM in an animal model as was extensively evidenced previously [27-30]. The objective of this study was to investigate the potential of transplanting undifferentiated hUCMSCs and ILCs generated from differentiation in the treatment of diabetic rats via various ways of transplantation. Our results demonstrated that transplanting newly generated ILCs either via the tail vein or intraperitoneally attenuated hyperglycemia effectively in vivo.

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