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, 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 and Pimanda, John E. (2016) PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells. Proc Natl Acad Sci U S A, 113 16: E2306-E2315. doi:10.1073/pnas.1518244113


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.
Title PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells
Journal name Proc Natl Acad Sci U S A   Check publisher's open access policy
ISSN 1091-6490
0027-8424
Publication date 2016-04-19
Year available 2016
Sub-type Article (original research)
DOI 10.1073/pnas.1518244113
Open Access Status Not Open Access
Volume 113
Issue 16
Start page E2306
End page E2315
Total pages 10
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Collection year 2017
Language eng
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 lineagecommitted 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.
Keyword Platelet-derived growth factor-AB
5-Azacytidine
Tissue regeneration
Multipotent stem cells
Cell reprogramming
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
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Created: Wed, 27 Jul 2016, 14:48:21 EST by Amelie Casgrain on behalf of School of Medicine