Wharton’s Jelly Mesenchymal Stem Cells as Candidates for Beta Cells Regeneration: Extending the Differentiative and Immunomodulatory Benefits of Adult Mesenchymal Stem Cells for the Treatment of Type 1 Diabetes

Abstract

Mesenchymal stem cells (MSC) are uniquely capable of crossing germinative layers borders (i.e. are able to differentiate towards ectoderm-, mesoderm- and endoderm-derived cytotypes) and are viewed as promising cells for regenerative medicine approaches in several diseases. Type I diabetes therapy should potentially benefit from such differentiated cells: the search for alternatives to organ/islet transplantation strategies via stem cells differentiation is an ongoing task, significant goals having been achieved in most experimental settings (e.g. insulin production and euglycaemia restoration), though caution is still needed to ensure safe and durable effects in vivo. MSC are obtainable in high numbers via ex vivo culture and can be differentiated towards insulin-producing cells (IPC). Moreover, recent reports evidenced that MSC possess immunomodulatory activities (acting on both innate and acquired immunity effectors) which should result in a reduction of the immunogenicity of transplanted cells, thus limiting rejection. Moreover it has been proposed that MSC administration should be used to attenuate the autoimmune processes which lead to the destruction of beta cells. This review illustrates the recent advances made in differentiating human MSC to IPC. In particular, we compare the effectiveness of the differentiation protocols applied, the markers and functional assays used to characterize differentiated progeny, and the in vivo controls. We further speculate on how MSC derived from Wharton's jelly of human umbilical cord may represent a more promising regenerative medicine tool, as recently demonstrated for endoderm-derived organs (as liver) in human subjects, also considering their peculiar immunomodulatory features compared to other MSC populations.

Pluripotent Stem Cells in Bone Marrow and Cord Blood

“…are able to differentiate towards ectoderm-, mesoderm-and endoderm-derived cell types) and do not express the major histocompatibility complex (MHC) class II Human Leukocyte Antigen (HLA-DR) antigens. This, together with their in vitro proliferative potential and their immunoregulatory properties, renders them extremely promising for regenerative medicine applications in several diseases [7].…”

In Vitro Studies of Horse Umbilical Cord Matrix-Derived Cells: From Characterization to Labeling for Magnetic Resonance Imaging

“…Due to their primitive embryonic stem-cell-like characteristics, UCM-derived cells, when exposed to specific stimuli, have the ability to differentiate into multiple germ layers including mesoderm in horses [9,10,13] and ectoderm in pigs [8,14] and horses [9,11]. Others: SOX2+ [9][10][11][12] Swine Embryonic cell markers: OCT-3/4+ Others: SOX2+, NANOG+ [8] As in human medicine (for review see [7,15,16]), also in veterinary medicine an important property to evaluate stem cells is to assess their usefulness in allogenic regenerative medicine. To test the immunological properties of UCM-derived cells, Carrade et al, (2010) studied healthy horses following a single intra-articular injection of autologous and allogeneic MSCs from equine UCM and found no significant differences between the degree and type of inflammation elicited by self and non-self-MSC [17].…”

Perinatal sources of mesenchymal stem cells: Wharton’s jelly, amnion and chorion

“…Stem cells isolated from Wharton's jelly are a highly homogeneous population of cells, which distinguishes these cells from the population of many other somatic stem cells. It has been shown that UC-MSCs may differentiate into several lineages, including adipose cells, chondrocytes, osteoblasts, neuronal cells, endothelial cells, cardiomyocytes, hepatocyte-like and pancreas beta cells [26][27][28]. In this context, UC-MSCs are an example of multipotent or even pluripotent stem cells.…”