Journal Article

Islet-Like Clusters Derived from Mesenchymal Stem Cells in Wharton's Jelly of the Human Umbilical Cord for Transplantation to Control Type 1 Diabetes

Fu, Yu Show, Liu, Shing Hwa, Chao, Kuo Fang, Chao, Kuo Ching

2008

Overview

There is a widespread interest in developing renewable sources of islet-replacement tissue for type I diabetes mellitus. Human mesenchymal cells isolated from the Wharton's jelly of the umbilical cord (HUMSCs), which can be easily obtained and processed compared with embryonic and bone marrow stem cells, possess stem cell properties. HUMSCs may be a valuable source for the generation of islets. HUMSCs were induced to transform into islet-like cell clusters in vitro through stepwise culturing in neuron-conditioned medium. To assess the functional stability of the islet-like cell clusters in vivo, these cell clusters were transplanted into the liver of streptozotocin-induced diabetic rats via laparotomy. Glucose tolerance was measured on week 12 after transplantation accompanied with immunohistochemistry and electron microscopy analysis. These islet-like cell clusters were shown to contain human C-peptide and release human insulin in response to physiological glucose levels. Real-time RT-PCR detected the expressions of insulin and other pancreatic beta-cell-related genes (Pdx1, Hlxb9, Nkx2.2, Nkx6.1, and Glut-2) in these islet-like cell clusters. The hyperglycemia and glucose intolerance in streptozotocin-induced diabetic rats was significantly alleviated after xenotransplantation of islet-like cell clusters, without the use of immunosuppressants. In addition to the existence of islet-like cell clusters in the liver, some special fused liver cells were also found, which characterized by human insulin and nuclei-positive staining and possessing secretory granules. In this study, we successfully differentiate HUMSCs into mature islet-like cell clusters, and these islet-like cell clusters possess insulin-producing ability in vitro and in vivo. HUMSCs in Wharton's Jelly of the umbilical cord seem to be the preferential source of stem cells to convert into insulin-producing cells, because of the large potential donor pool, its rapid availability, no risk of discomfort for the donor, and low risk of rejection.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Apoptosis / Base Sequence / Biotechnology/Chemical Biology of the Cell / Blood Glucose - metabolism / Bone marrow / Cardiomyocytes / Cell Differentiation / Cell Line / Cell Transplantation / Cluster analysis / Clusters / Comparative analysis / Conditioning / Diabetes / Diabetes and Endocrinology/Type 1 Diabetes / Diabetes mellitus / Diabetes Mellitus, Type 1 - surgery / Diabetes therapy / Diagnosis / Discomfort / DNA Primers / Electron microscopy / Embryo cells / Gastroenterology and Hepatology/Pancreas / Glucose / Glucose tolerance / Graft rejection / Hepatocytes / Human behavior / Humans / Hyperglycemia / Immunohistochemistry / Immunological tolerance / Immunosuppressive agents / Insulin / Insulin - blood / Intolerance / Islets of Langerhans - cytology / Liver / Liver transplantation / Liver transplants / Medicine / Mesenchymal stem cells / Mesenchyme / Metabolism / Nervous system / Neurons / Nkx2.2 protein / Nuclei (cytology) / Pancreas / Physiological aspects / Polymerase chain reaction / Rats / Rodents / Secretory vesicles / Stability analysis / Stem cell transplantation / Stem cells / Streptozocin / Studies / Toxicology / Transplantation / Transplants & implants / Type 1 diabetes / Umbilical cord / Umbilical Cord - transplantation / Xenografts / Xenotransplantation