PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells
Autor: | Ralph J. Mobbs, Lies Boelen, Amadeus Gladbach, Ashwin Unnikrishnan, Philip Hardy, William R. Walsh, Jeanette E. Villanueva, Avani Yeola, Louise E. Purton, Vashe Chandrakanthan, Yan Yu, Carl R. Walkley, Shane T. Grey, Alexander Macmillan, John E. Pimanda, Peter Zarzour, Lars M. Ittner, Robyn L. Ward, Qiao Qiao, Andrea Nuñez, Kathy Knezevic, Jair C. Kwan, Young Chan Kang, Luke B. Hesson, Jason W. H. Wong, Cintia Palu, Fabien Delerue, Rabab Nasrallah, Dominik Beck, Michael Carnell, Rema A. Oliver, Renee Whan |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Cellular differentiation Induced Pluripotent Stem Cells Clinical uses of mesenchymal stem cells Mice Transgenic tissue regeneration Biology 03 medical and health sciences Mice stem cells Animals Cells Cultured Stem cell transplantation for articular cartilage repair Platelet-Derived Growth Factor Multidisciplinary Mesenchymal Stromal Cells cell reprogramming 5-Azacytidine Amniotic stem cells Mesenchymal Stem Cells multipotent Cellular Reprogramming Molecular biology Neural stem cell Cell biology 030104 developmental biology PNAS Plus Multipotent Stem Cell Organ Specificity Azacitidine platelet-derived growth factor-AB Stem cell Adult stem cell |
Popis: | Current approaches in tissue engineering are geared toward generating tissue-specific stem cells. Given the complexity and heterogeneity of tissues, this approach has its limitations. An alternate approach is to induce terminally differentiated cells to dedifferentiate into multipotent proliferative cells with the capacity to regenerate all components of a damaged tissue, a phenomenon used by salamanders to regenerate limbs. 5-Azacytidine (AZA) is a nucleoside analog that is used to treat preleukemic and leukemic blood disorders. AZA is also known to induce cell plasticity. We hypothesized that AZA-induced cell plasticity occurs via a transient multipotent cell state and that concomitant exposure to a receptive growth factor might result in the expansion of a plastic and proliferative population of cells. To this end, we treated lineage-committed cells with AZA and screened a number of different growth factors with known activity in mesenchyme-derived tissues. Here, we report that transient treatment with AZA in combination with platelet-derived growth factor–AB converts primary somatic cells into tissue-regenerative multipotent stem (iMS) cells. iMS cells possess a distinct transcriptome, are immunosuppressive, and demonstrate long-term self-renewal, serial clonogenicity, and multigerm layer differentiation potential. Importantly, unlike mesenchymal stem cells, iMS cells contribute directly to in vivo tissue regeneration in a context-dependent manner and, unlike embryonic or pluripotent stem cells, do not form teratomas. Taken together, this vector-free method of generating iMS cells from primary terminally differentiated cells has significant scope for application in tissue regeneration. |
Databáze: | OpenAIRE |
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