Human fetal pancreatic insulin-producing cells proliferate in vitro
| Autor: | Mugdha V. Joglekar, Sheela V Joglekar, Vinay M. Joglekar, Anandwardhan A. Hardikar |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
medicine.medical_specialty Endocrinology Diabetes and Metabolism Cell Culture Techniques Enteroendocrine cell Gestational Age Biology Epigenesis Genetic Histones Endocrinology Fetus Pregnancy Internal medicine Insulin-Secreting Cells medicine Humans Insulin Epigenetics Promoter Regions Genetic Pancreas Cells Cultured Cell Proliferation Pancreatic islets Mesenchymal stem cell Histone-Lysine N-Methyltransferase In vitro Chromatin medicine.anatomical_structure Cell culture Histone Methyltransferases Female |
| Zdroj: | The Journal of endocrinology. 201(1) |
| ISSN: | 1479-6805 |
| Popis: | There have been considerable efforts towards understanding the potential of human pancreatic endocrine cells to proliferate and transition into mesenchymal cell populations. Since rodent studies have demonstrated that mouse insulin-producing cells do not proliferate in vitro, a similar possibility has been considered for human islet endocrine cells. Considering the inherent differences in mouse and human pancreatic islets, we decided to assess the potential of human fetal pancreatic insulin-producing cells to proliferate in vitro. We studied the proliferative potential of human fetal pancreatic islet-derived populations from second or third trimester fetal pancreas and characterized the cells that grow out during their expansion. We have used seven different approaches including in situ hybridization and immunostaining, quantitative estimation of multiple gene transcripts in populations as well as in single cells, clonal analysis of islet cells, assessment of heritable marks of active insulin promoter, and thymidine analog-based lineage tracing. Our studies demonstrate that human fetal pancreatic insulin-producing cells proliferate in vitro to generate mesenchymal cell populations. Interestingly, epigenetic modifications that mark open chromatin conformation of insulin promoter regions are retained even after a million fold expansion/proliferation in vitro. These findings demonstrate that hormone-producing cells in pancreatic islets proliferate in vitro and retain epigenetic marks that characterize an active insulin promoter. Such in vitro-derived mesenchymal cells may be of potential use in cell-replacement therapy for diabetes. |
| Databáze: | OpenAIRE |
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