{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:38:12Z","timestamp":1785753492427,"version":"3.56.0"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Stem cell therapy has shown immense promise in treating genetic disorders, particularly muscular diseases like Duchenne muscular dystrophy (DMD). This study investigates a novel method to enhance the viability of stem cell transplants in DMD by upregulating Programmed Death Ligand 1 (PD-L1) in muscle stem cells (MuSCs) through preconditioning with hypoxia and\/or interferon-\u03b3 (IFN-\u03b3) to mitigate T cell immune rejection. MuSCs were treated with 5% hypoxia for 72\u00a0h and further treated with IFN-\u03b3 to enhance PD-L1 expression. Additionally, gain and loss experiments using a PD-L1 inhibitor (BMS-1) were conducted to investigate cellular expression profiles <jats:italic>in vitro<\/jats:italic> and cell transplantation outcomes <jats:italic>in vivo<\/jats:italic>. Our results showed significant upregulation of PD-L1 in MuSCs under hypoxia and IFN-\u03b3 conditions without affecting cellular proliferation and differentiation <jats:italic>in vitro<\/jats:italic>. <jats:italic>In vivo<\/jats:italic>, these preconditioned MuSCs led to decreased infiltration of CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells in implanted limb muscles of mouse models. Blocking PD-L1 reduced graft survival in muscles treated with MuSCs. Conversely, increased PD-L1 expression and reduced T cell infiltration correlated with improved graft survival, as identified by pre-labeled LacZ + MuSCs following transplantation. This study provides evidence that hypoxia and IFN-\u03b3 preconditioning of MuSCs can significantly enhance the efficacy of cell therapy for DMD by mitigating immune rejection. Our strategic approach aimed to improve donor cell survival and function post-transplantation by modifying immune responses towards the donor cells.<\/jats:p>","DOI":"10.3389\/fphar.2024.1471563","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T08:29:43Z","timestamp":1730449783000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Hypoxia-induced PD-L1 expression and modulation of muscle stem cell allograft rejection"],"prefix":"10.3389","volume":"15","author":[{"given":"Jacob","family":"Raiten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve M.","family":"Abd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane B.","family":"Handelsman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshank V.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer C.","family":"Ku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata M.","family":"Parsons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan L.","family":"Wassink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheridan L.","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Overbay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.stemcr.2021.11.012","article-title":"Tubastatin A maintains adult skeletal muscle stem cells in a quiescent state ex vivo and improves their engraftment ability in vivo","volume":"17","author":"Arjona","year":"2022","journal-title":"Stem Cell Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e150846","DOI":"10.1172\/JCI150846","article-title":"Targeting HIF-1\u03b1 abrogates PD-L1-mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues","volume":"132","author":"Bailey","year":"2022","journal-title":"J. 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