Pancreatic mesenchymal stromal cells: Characteristics and possible origin

Mesenchymal stromal cells (MSCs) are heterogeneous group of cells with multipotent capability that were primarily isolated from bone marrow. Many reports suggest that MSCs reside in almost all tissues and organs. Pancreatic stem cells are of great clinical interest due to their potential role in treatment of diabetes mellitus (DM). MSCs were isolated from both adult and fetal pancreatic tissues. These cells resemble bone marrow MSCs regarding their surface markers expression and mesodermal differentiation potential. Pancreatic MSCs are also able to differentiate into pancreatic endocrine lineage cells, suggesting a possible source for cell replacement therapy for DM. In this review, we will discuss the characterization of pancreatic MSCs, their possible origin and their use as cell therapy for diabetes. Introduction Mesenchymal stromal cells (MSCs) are heterogeneous population of cells that were primarily isolated from the bone marrow [1]. MSC-like cells have been isolated from other tissues like the human placenta [2], peripheral blood [3], umbilical cord [4], adipose tissue [5], endometrium [6] and pancreas [7,8]. According to the definition of the International Society for Cell Therapy, MSCs are characterized by being plastic-adherent in standard culture condition and can be differentiated in vitro into osteoblasts, chondroblasts and adipocytes [9-11]. They express certain surface markers such as CD105, CD90, CD73, while lack the expression of CD45, CD34, CD14, CD11b, CD79 alpha, CD19 and HLA-DR. Animal experiments showed that MSCs could engraft into wounds, and contribute to remodeling of injured tissues [10,11]. MSC transplantation has shown promising results in treatment of diseases such as diabetes [12-14], autoimmune diseases [15-17], brain repair [18,19], and blood malignancies [20,21] In this review, we will examine the characteristics of pancreatic MSCs, their possible origin and their role in cell replacement therapy for diabetes. Characteristics and origin of pancreatic MSCs MSCs isolated from exocrine pancreatic culture MSCs were isolated from exocrine tissue culture (culture that includes both acinar and duct epithelial cells [7,8,22-24]. They resembled bone marrow MSCs both morphologically and in their capability to Origin of MSCs isolated from pancreatic exocrine tissue culture As bone marrow MSCslike cells have been isolated from different tissues, it was hypothesized that organ MSCs may represent a population of migrating bone marrow MSCs, that “home” to the pancreas [25,26]. In support of this hypothesis, tracking bone marrow MSCs has shown that they populate the pancreatic tissue, and that pancreatic MSCs found in culture were shown to be derived from marrow MSCs [23,27]. A contradictory proposal was suggested by Lechner et al. [28] who showed that bone marrow do not contribute to pancreatic regeneration nor turnover [28]. This was proven through transplantation of green fluorescent protein positive (GFP), sex-mismatched bone marrow into mice. while blood cells acquired full donor chimerism, however, examination of more than 100,000 β-cells showed no GFP positive β-cells [28]. Epithelial to mesenchymal transition process(EMT) was suggested as a possible mechanism of generation of mesenchymal stem cells from cultured exocrine acinar and duct cells [22,24,29,]. EMT is a process in which epithelial cells change their phenotype to become mesenchymal cells [30,31]. For this change to occur, epithelial cells lose many of their specific structures and functions, such as cell-cell contact and their cellular polarity while gain the ability to migrate and invade the surrounding tissues. For EMT process to happen, certain cellular changes should occur. First, a change in the epithelial cell shape due to loss of cellular polarity; epithelial cells become spindle in shape. This change in the shape is mediated by the decrease in the expression of the adhesion molecules differentiate into osteoblasts, adipocytes and chondroblasts [7,8,22,23]. Interestingly, pancreatic MSCs isolated from exocrine pancreatic cultures were also shown to generate pancreatic endocrine progenitors. Upon expansion of MSCs isolated from exocrine pancreatic tissues, they expressed endocrine progenitor markers such as Isl1, Nkx2.2, Nkx6.1, nestin, Ngn3, PDX1, and NeuroD [8]. Likewise, MSCs isolated from pancreatic duct tissue cultures expressed pancreatic endocrine progenitor markers such as PAX4 and Ngn3, when induced to differentiate into cells of endocrine lineage [7]. Correspondence to: Nagwa El-Badri, M.D., Ph.D, Director, Center of Excellence of Stem Cells, Zewail City of Science and Technology, Cairo, Egypt, Tel: +20 2 385 40 401; E-mail: nelbadri@zewailcity.edu. eg