Immunohistochemical Localization of Stem Cell-Related Markers (CD133, Nestin and Bmi-1) and mTOR in the Pancreas of Rat Models of Type 1 and Type 2 Diabetes Mellitus

Research Article

J Stem Cells Res, Rev & Rep. 2014;1(1): 1004.

Immunohistochemical Localization of Stem Cell-Related Markers (CD133, Nestin and Bmi-1) and mTOR in the Pancreas of Rat Models of Type 1 and Type 2 Diabetes Mellitus

Murata E1, Matsumoto S2, Shuto M1 and Akita M2*

1Department of Health and Medical Care, Saitama Medical University, Japan

2Division of Morphological Science, Biomedical Research Center, Saitama Medical University, Japan

*Corresponding author: Masumi Akita, Division of Morphological Science, Biomedical Research Center, Saitama Medical University, 38 Moroyama, Iruma-gun, Saitama 350-0495, Japan

Received: Aug 07, 2014; Accepted: Aug 20, 2014; Published: Aug 21, 2014

Abstract

Stem cell-related markers (CD133, nestin and Bmi-1) and mammalian target of rapamycin (mTOR) were detected in the pancreas of rat models of type 1 and type 2 Diabetes Mellitus (DM). As a model of type 1 DM, Komeda Diabetes-Prone (KDP) rat and control rat (KND rat) were used. As a model of type 2 DM, spontaneously diabeticTorii (SDT) rat and control rat (SD rat) were used. In each control rat, pancreatic islets were strongly positive for CD133, nestin, Bmi-1and mTOR. In the KDP rat, CD133, nestin, Bmi-1and mTOR positive cells did not show cellular mass like pancreatic islets. These positive cells were associated with invasion by mononuclear cells. Partial acinar cells showed increased immunoreactivity for CD133, Bmi-1 and mTOR, although nestin immunoreactivity was almost negative. In the SDT rat, CD133, nestin, Bmi-1and mTOR positive cells also did not show cellular mass like pancreatic islets. These positive cells were associated with increased fibrillar element. Strong immunoreactivity for CD133, Bmi-1 and mTOR was observed in the pancreatic ductal epithelial cells and partial acinar cells compared with control rat. Nestin immunoreactivity was almost negative. Although β-cell denaturation in the pancreatic islet is present in the rat models of DM, pancreatic acinar and ductal epithelial cells express immunoreactivity for CD133, Bmi-1 and mTOR. Present study suggests that pancreatic acinar and ductal epithelial cells expressing CD133, Bmi-1 and mTOR are considerable as an alternative source of pancreatic stem/progenitors, even individuals who showed a diabetic condition.

Keywords: CD133; Nestin; Bmi-1; mTOR; Type 1 diabetes; Type 2 diabetes; KDP rat; SDT rat; Pancreas

Introduction

Type 1 and type 2 Diabetes Mellitus (DM) are the two main forms of DM. Both types are characterized by progressive β-cell failure in the pancreatic islet [1]. In type 1 DM, this is typically caused by an autoimmune assault against the β-cells, inducing progressive β-cell death [1]. The pathogenesis of type 2 DM is more variable, comprising different degrees of β-cell failure relative to varying degrees of insulin resistance [1]. Pancreatic islet transplantation is a promising method to restore functional islet β-cell mass for patients with DM [2]. Pancreatic islet transplants hold significant potential advantages over whole-gland transplants [3]. However, pancreatic islet transplantation is associated with several clinically relevant risks [4-6]. Because of the limited supply of human donor islets, it is critical that new strategies are explored as alternative renewable sources of transplantation [7]. Stem cells are characterized by extensive proliferation and multilineage differentiation capacity [8]. Mouse embryonic stem cells differentiate into cells of all three primary germ layers including endodermal cells that produce insulin in vitro [9]. Transplanted embryonicstem cells [9-11] and fetal pancreatic progenitor cells [12, 13] have been successfully used to treat DM in murine models. Multipotent adult stem cells are harvested from bone marrow [14,15], adipose tissue [16] and umbilical cord and placenta [17]. Stem cells, as alternative islet cell sources, may be a valuable source for cell replacement therapy. In the pancreatic islet, CD133 [18,19], nestin [7,20-22] and B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) [23] have been reported as molecular markers of pancreatic stem cells. Recently, Yilmaz et al. [24] show that reduction in caloric intake inhibits the nutrientsensitive kinase mammalian target of rapamycin (mTOR) pathway and amplify intestinal stem cell numbers during caloric restriction.