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Moreover, it causes progressive heterotopic ossification (HO) in connective tissues. Using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) and mouse models, we elucidated the underlying mechanisms of FOP pathogenesis and identified a candidate drug for FOP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In the current study, healthy mesenchymal stem\/stromal cells derived from iPSCs (iMSCs) expressing ACVR2B-Fc (iMSC\n                      <jats:sup>ACVR2B-Fc<\/jats:sup>\n                      ), which is a neutralizing receptobody, were constructed. Furthermore, patient-derived iMSCs and FOP mouse model (ACVR1\n                      <jats:sup>R206H<\/jats:sup>\n                      , female) were used to confirm the inhibitory function of ACVR2B-Fc fusion protein secreted by iMSC\n                      <jats:sup>ACVR2B-Fc<\/jats:sup>\n                      on BMP signaling pathways and HO development, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that secreted ACVR2B-Fc attenuated BMP signaling initiated by Activin-A and BMP-9 in both iMSCs and FOP-iMSCs in vitro. Transplantation of ACVR2B-Fc-expressing iMSCs reduced primary HO in a transgenic mouse model of FOP. Notably, a local injection of ACVR2B-Fc-expressing iMSCs and not an intraperitoneal injection improved the treadmill performance, suggesting compound effects of ACVR2B-Fc and iMSCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results offer a new perspective for treating FOP through stem cell therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13287-024-03691-7","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T16:01:32Z","timestamp":1710777692000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["iMSC-mediated delivery of ACVR2B-Fc fusion protein reduces heterotopic ossification in a mouse model of fibrodysplasia ossificans progressiva"],"prefix":"10.1186","volume":"15","author":[{"given":"Pan","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Inada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitsu","family":"Hotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3930-8032","authenticated-orcid":false,"given":"Makoto","family":"Ikeya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"3691_CR1","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/ng1783","volume":"38","author":"EM Shore","year":"2006","unstructured":"Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho T-J, Choi IH, et al. 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Written informed consent was provided by each donor. All animal experiments were approved by the institutional animal committee of Kyoto University (Research on development of regenerative medicine using pluripotent stem cell-derived stem cells (#16\u201373, 04\/01\/2016\u201303\/31\/2022), Ectopic bone origin exploration study using model mice (#22\u2013154, 04\/01\/2022\u2013), Development of a treatment for fibrodysplasia ossificans progressiva using a mouse model (#23\u2013218, 08\/22\/2023\u2013).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"83"}}