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Respiration deficiency, disruption in energy metabolism, and consequently OS induction change the biophysical, biochemical, and cellular components of the native tissue. Additionally, the homeostatic molecular players and cell signaling might be changed. Despite all aforementioned issues, in the native stem cell niche, physiological hypoxia is not toxic; rather, it is vitally required for homing, self\u2010renewal, and differentiation. Hence, the key macromolecular players involved in the support of stem cell survival and re\u2010adaptation to a new dysfunctional niche must be understood for managing the cell therapy outcome. Hypoxia\u2010inducible factor 1\u2010alpha is the master transcriptional regulator, involved in the cell response to hypoxia and the adaptation of stem cells to a new niche. This protein is regulated by interaction with sirtuins. Sirtuins are highly conserved NAD+\u2010dependent enzymes that monitor the cellular energy status and modulate gene transcription, genome stability, and energy metabolism in response to environmental signals to modulate the homing and fate of stem cells. Herein, new insights into the nesting of stem cells in hypoxic\u2013ischemic injured tissues were provided and their programming in a new dysfunctional niche along with the involved complex macromolecular players were critically discussed.<\/jats:p>","DOI":"10.1002\/biof.1674","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T04:12:07Z","timestamp":1600315927000},"page":"6-20","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nesting and fate of transplanted stem cells in hypoxic\/ischemic injured tissues: The role of<scp>HIF1\u03b1<\/scp>\/sirtuins and downstream molecular interactions"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8429-3618","authenticated-orcid":false,"given":"Abolfazl","family":"Barzegari","sequence":"first","affiliation":[{"name":"Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute Tabriz University 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