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PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells
Chandrakanthan, Vashe Yeola, Avani Kwan, Jair C. Oliver, Rema A. Qiao, Qiao Kang, Young Chan Zarzour, Peter Beck, Dominik Boelen, Lies Unnikrishnan, Ashwin
Chandrakanthan, Vashe
Yeola, Avani
Kwan, Jair C.
Oliver, Rema A.
Qiao, Qiao
Kang, Young Chan
Zarzour, Peter
Beck, Dominik
Boelen, Lies
Unnikrishnan, Ashwin
Author
Chandrakanthan, Vashe
Yeola, Avani
Kwan, Jair C.
Oliver, Rema A.
Qiao, Qiao
Kang, Young Chan
Zarzour, Peter
Beck, Dominik
Boelen, Lies
Unnikrishnan, Ashwin
Villanueva, Jeanette E.
Nunez, Andrea C.
Knezevic, Kathy
Palu, Cintia
Nasrallah, Rabab
Carnell, Michael
Macmillan, Alex
Whan, Renee
Yu, Yan
Hardy, Philip
Grey, Shane T.
Gladbach, Amadeus
Delerue, Fabien
Ittner, Lars
Mobbs, Ralph
Walkley, Carl R.
Purton, Louise E.
Ward, Robyn L.
Wong, Jason W. H.
Hesson, Luke B.
Walsh, William
Pimanda, John E.
Yeola, Avani
Kwan, Jair C.
Oliver, Rema A.
Qiao, Qiao
Kang, Young Chan
Zarzour, Peter
Beck, Dominik
Boelen, Lies
Unnikrishnan, Ashwin
Villanueva, Jeanette E.
Nunez, Andrea C.
Knezevic, Kathy
Palu, Cintia
Nasrallah, Rabab
Carnell, Michael
Macmillan, Alex
Whan, Renee
Yu, Yan
Hardy, Philip
Grey, Shane T.
Gladbach, Amadeus
Delerue, Fabien
Ittner, Lars
Mobbs, Ralph
Walkley, Carl R.
Purton, Louise E.
Ward, Robyn L.
Wong, Jason W. H.
Hesson, Luke B.
Walsh, William
Pimanda, John E.
Abstract
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.
Keywords
platelet-derived growth factor-AB, 5-Azacytidine, tissue regeneration, multipotent, stem cells, cell reprogramming
Date
2016
Type
Journal article
Journal
Proceedings of the National Academy of Sciences of USA
Book
Volume
113
Issue
16
Page Range
E2306-E2315
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
File Access
Open