Human Insulin Secreted from Insulinogenic Xenograft Restores Normoglycemia in Type 1 Diabetic Mice without Immunosuppression
| Autor: | J. Kim, S. Park, H. M. Kang, C. W. Ahn, H. C. Kwon, J. H. Song, Y. J. Lee, K. H. Lee, H. Yang, S. Y. Baek, S. H. Yoo, S. H. Kim, H. Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Cell Transplantation, Vol 21 (2012) |
| Druh dokumentu: | article |
| ISSN: | 0963-6897 1555-3892 68488602 |
| DOI: | 10.3727/096368912X636803 |
| Popis: | In the present study, we examined the therapeutic potential of human amnion-derived insulin-secreting cells for type 1 diabetes. Human amniotic mesenchymal stem cells (hAMs) were isolated from amnion and cultivated to differentiate into insulin-secreting cells in vitro. After culture in vitro, the differentiated cells (hAM-ISCs) were intensively stained with dithizone and secreted insulin and c-peptide in a high-glucose-dependent manner. They expressed mRNAs of pancreatic cell-related genes, including INS, PDX1, Nkx6-1, NEUROG3, ISL1, NEUROD1, GLUT1, GLUT2, PC1/3, PC2, GCK, PPY, SST, and GC, and were positive for human insulin and c-peptide. Transplantation of hAM-ISCs into the kidneys of mice with streptozotocin-induced diabetes restored body weight and normalized the blood glucose levels, which lasted for 210 days. Only human insulin and c-peptide were detected in the blood of normalized mice after 2 months of transplantation, but little mouse insulin and c-peptide. Removal of graft-bearing kidneys from these mice resulted in causing hyperglycemia again. Human cell-specific gene, hAlu, and human pancreatic cell-specific genes, insulin, PDX1, GLUT1, GLP1R, Nkx6-1, NEUROD1, and NEUROG3, were detected in the graft-bearing kidneys. Colocalization of human insulin and human nuclei antigen was also observed. These results demonstrate that hAMs could differentiate into functional insulin-secreting cells in vitro, and human insulin secreted from hAM-ISCs following transplantation into type 1 diabetic mice could normalize hyperglycemia, overcoming immune rejection for a long period. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
|