+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Improved differentiation of umbilical cord blood-derived mesenchymal stem cells into insulin-producing cells by PDX-1 mRNA transfection



Improved differentiation of umbilical cord blood-derived mesenchymal stem cells into insulin-producing cells by PDX-1 mRNA transfection



Differentiation; Research in Biological Diversity 87(5): 200-208



Numerous studies have sought to identify diabetes mellitus treatment strategies with fewer side effects. Mesenchymal stem cell (MSC) therapy was previously considered as a promising therapy; however, it requires the cells to be trans-differentiated into cells of the pancreatic-endocrine lineage before transplantation. Previous studies have shown that PDX-1 expression can facilitate MSC differentiation into insulin-producing cells (IPCs), but the methods employed to date use viral or DNA-based tools to express PDX-1, with the associated risks of insertional mutation and immunogenicity. Thus, this study aimed to establish a new method to induce PDX-1 expression in MSCs by mRNA transfection. MSCs were isolated from human umbilical cord blood and expanded in vitro, with stemness confirmed by surface markers and multipotentiality. MSCs were transfected with PDX-1 mRNA by nucleofection and chemically induced to differentiate into IPCs (combinatorial group). This IPC differentiation was then compared with that of untransfected chemically induced cells (inducer group) and uninduced cells (control group). We found that PDX-1 mRNA transfection significantly improved the differentiation of MSCs into IPCs, with 8.3±2.5% IPCs in the combinatorial group, 3.21±2.11% in the inducer group and 0% in the control. Cells in the combinatorial group also strongly expressed several genes related to beta cells (Pdx-1, Ngn3, Nkx6.1 and insulin) and could produce C-peptide in the cytoplasm and insulin in the supernatant, which was dependent on the extracellular glucose concentration. These results indicate that PDX-1 mRNA may offer a promising approach to produce safe IPCs for clinical diabetes mellitus treatment.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 053743924

Download citation: RISBibTeXText

PMID: 25201603

DOI: 10.1016/j.diff.2014.08.001


Related references

Mechanism study for hypoxia induced differentiation of insulin-producing cells from umbilical cord blood-derived mesenchymal stem cells. Biochemical and Biophysical Research Communications 466(3): 444-449, 2015

Notch signaling: a novel regulating differentiation mechanism of human umbilical cord blood-derived mesenchymal stem cells into insulin-producing cells in vitro. Chinese Medical Journal 123(5): 606-614, 2010

In Vitro Differentiation of Human Umbilical Cord Blood CD133(+)Cells into Insulin Producing Cells in Co-Culture with Rat Pancreatic Mesenchymal Stem Cells. Cell Journal 17(2): 211-220, 2015

Generation of glucose-responsive, insulin-producing cells from human umbilical cord blood-derived mesenchymal stem cells. Cell Transplantation 21(6): 1321-1339, 2012

Extracellular matrix gel is necessary for in vitro cultivation of insulin producing cells from human umbilical cord blood derived mesenchymal stem cells. Chinese Medical Journal 121(9): 811-818, 2008

Study on differentiation of mesenchymal stem cells derived from human umbilical cord blood into insulin secreting cells. Zhonghua Xue Ye Xue Za Zhi 29(10): 679-683, 2008

Differentiation of umbilical cord derived mesenchymal stem cells to hepatocyte cells by transfection of miR-106a, miR-574-3p, and miR-451. Gene 667: 1-9, 2018

Transfection of hBMP-2 into mesenchymal stem cells derived from human umbilical cord blood and bone marrow induces cell differentiation into chondrocytes. Minerva Medica 105(4): 283-288, 2014

Immunogenicity of insulin-producing cells derived from human umbilical cord mesenchymal stem cells. Experimental and Therapeutic Medicine 13(4): 1456-1464, 2017

Human umbilical cord blood-derived stromal cells are superior to human umbilical cord blood-derived mesenchymal stem cells in inducing myeloid lineage differentiation in vitro. Stem Cells and Development 21(9): 1429-1440, 2012

Transplantation of insulin-producing cells derived from umbilical cord stromal mesenchymal stem cells to treat NOD mice. Cell Transplantation 20(3): 455-466, 2011

Differentiation of PDX1 gene-modified human umbilical cord mesenchymal stem cells into insulin-producing cells in vitro. International Journal of Molecular Medicine 28(6): 1019-1024, 2011

Human umbilical cord mesenchymal stem cells derived from Wharton's jelly differentiate into insulin-producing cells in vitro. Chinese Medical Journal 124(10): 1534-1539, 2011

Comparison of different methods for the isolation of mesenchymal stem cells from umbilical cord matrix: proliferation and multilineage differentiation as compared to mesenchymal stem cells from umbilical cord blood and bone marrow. Cell Biology International 2013:, 2013

In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells. Biochemical and Biophysical Research Communications 330(4): 1153-1161, 2005