File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Pdgf-ab and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells

TitlePdgf-ab and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells
Authors
KeywordsMultipotent stem cells
Platelet-derived growth factor-AB
Tissue regeneration
5-Azacytidine
Cell reprogramming
Issue Date2016
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2016, v. 113, n. 16, p. E2306-E2315 How to Cite?
AbstractCurrent 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.
Persistent Identifierhttp://hdl.handle.net/10722/251155
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChandrakanthan, Vashe-
dc.contributor.authorYeola, Avani-
dc.contributor.authorKwan, Jair C.-
dc.contributor.authorOliver, Rema A.-
dc.contributor.authorQiao, Qiao-
dc.contributor.authorKang, Young Chan-
dc.contributor.authorZarzour, Peter-
dc.contributor.authorBeck, Dominik-
dc.contributor.authorBoelen, Lies-
dc.contributor.authorUnnikrishnan, Ashwin-
dc.contributor.authorVillanueva, Jeanette E.-
dc.contributor.authorNunez, Andrea C.-
dc.contributor.authorKnezevic, Kathy-
dc.contributor.authorPalu, Cintia-
dc.contributor.authorNasrallah, Rabab-
dc.contributor.authorCarnell, Michael-
dc.contributor.authorMacmillan, Alex-
dc.contributor.authorWhan, Renee-
dc.contributor.authorYu, Yan-
dc.contributor.authorHardy, Philip-
dc.contributor.authorGrey, Shane T.-
dc.contributor.authorGladbach, Amadeus-
dc.contributor.authorDelerue, Fabien-
dc.contributor.authorIttner, Lars-
dc.contributor.authorMobbs, Ralph-
dc.contributor.authorWalkley, Carl R.-
dc.contributor.authorPurton, Louise E.-
dc.contributor.authorWard, Robyn L.-
dc.contributor.authorWong, Jason W.H.-
dc.contributor.authorHesson, Luke B.-
dc.contributor.authorWalsh, William-
dc.contributor.authorPimanda, John E.-
dc.date.accessioned2018-02-01T01:54:45Z-
dc.date.available2018-02-01T01:54:45Z-
dc.date.issued2016-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2016, v. 113, n. 16, p. E2306-E2315-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/251155-
dc.description.abstractCurrent 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.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectMultipotent stem cells-
dc.subjectPlatelet-derived growth factor-AB-
dc.subjectTissue regeneration-
dc.subject5-Azacytidine-
dc.subjectCell reprogramming-
dc.titlePdgf-ab and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1518244113-
dc.identifier.pmid27044077-
dc.identifier.scopuseid_2-s2.0-84964343832-
dc.identifier.volume113-
dc.identifier.issue16-
dc.identifier.spageE2306-
dc.identifier.epageE2315-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000374393800015-
dc.identifier.f1000726263494-
dc.identifier.issnl0027-8424-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats