Islet-like clusters derived from mesenchymal stem cells in Wharton's jelly of the human umbilical cord for transplantation to control type 1 diabetes
Journal
PLoS ONE
Journal Volume
3
Journal Issue
1
Date Issued
2008
Author(s)
Abstract
Background. There is a widespread interest in developing renewable sources of islet-replacement tissue for type 1 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. Methodology and Principal Findings. HUMSCs were incluted 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 β-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. Conclusions and Significance. 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. ? 2008 Chao et al.
Other Subjects
C peptide; glucose; glucose transporter 2; insulin; streptozocin; transcription factor PDX 1; insulin; primer DNA; animal cell; animal experiment; animal model; animal tissue; article; cell differentiation; cell fusion; controlled study; cord blood stem cell transplantation; culture medium; electron microscopy; gene expression; glucose intolerance; glucose tolerance; hepatocyte transplantation; human; human cell; hyperglycemia; immunohistochemistry; in vitro study; in vivo study; insulin dependent diabetes mellitus; insulin release; laparotomy; mesenchymal stem cell; nerve cell culture; nonhuman; pancreas islet beta cell; pancreas islet cell; rat; reverse transcription polymerase chain reaction; secretory granule; streptozocin diabetes; xenotransplantation; blood; cell line; cell transplantation; cytology; glucose blood level; insulin dependent diabetes mellitus; metabolism; nucleotide sequence; pancreas islet; transplantation; umbilical cord; Rattus; Base Sequence; Blood Glucose; Cell Differentiation; Cell Line; Cell Transplantation; Diabetes Mellitus, Type 1; DNA Primers; Humans; Immunohistochemistry; Insulin; Islets of Langerhans; Umbilical Cord
Type
journal article