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Type: Journal article
Title: Pdgf-ab and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells
Author: Chandrakanthan, V.
Yeola, A.
Kwan, J.
Oliver, R.
Qiao, Q.
Kang, Y.
Zarzour, P.
Beck, D.
Boelen, L.
Unnikrishnan, A.
Villanueva, J.
Nunez, A.
Knezevic, K.
Palu, C.
Nasrallah, R.
Carnell, M.
Macmillan, A.
Whan, R.
Yu, Y.
Hardy, P.
et al.
Citation: Proceedings of the National Academy of Sciences of USA, 2016; 113(16):E2306-E2315
Publisher: National Academy of Sciences of the United States of America
Issue Date: 2016
ISSN: 0027-8424
Statement of
Vashe Chandrakanthan, Avani Yeola, Jair C. Kwan, Rema A. Oliver, Qiao Qiao … Shane T. Grey … et al.
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
Rights: For volumes 106–114 (2009–September 2017), the author(s) retains copyright to individual articles, and NAS retains an exclusive License to Publish these articles and holds copyright to the collective work. Volumes 90–105 (1993–2008) are copyright © National Academy of Sciences. For volumes 1–89 (1915–1992), the author(s) retains copyright to individual articles, and NAS holds copyright to the collective work.
DOI: 10.1073/pnas.1518244113
Grant ID: ARC
Appears in Collections:Aurora harvest 3
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