{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T15:02:34Z","timestamp":1775746954989,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology of Taiwan","doi-asserted-by":"publisher","award":["MOST-104-2313-B-005-043-MY3"],"award-info":[{"award-number":["MOST-104-2313-B-005-043-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology of Taiwan","doi-asserted-by":"publisher","award":["MOE-112-S-0023-A"],"award-info":[{"award-number":["MOE-112-S-0023-A"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education","award":["MOST-104-2313-B-005-043-MY3"],"award-info":[{"award-number":["MOST-104-2313-B-005-043-MY3"]}]},{"name":"Ministry of Education","award":["MOE-112-S-0023-A"],"award-info":[{"award-number":["MOE-112-S-0023-A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hemophilia is a genetic disorder linked to the sex chromosomes, resulting in impaired blood clotting due to insufficient intrinsic coagulation factors. There are approximately one million individuals worldwide with hemophilia, with hemophilia A being the most prevalent form. The current treatment for hemophilia A involves the administration of clotting factor VIII (FVIII) through regular and costly injections, which only provide temporary relief and pose inconveniences to patients. In utero transplantation (IUT) is an innovative method for addressing genetic disorders, taking advantage of the underdeveloped immune system of the fetus. This allows mesenchymal stromal cells to play a role in fetal development and potentially correct genetic abnormalities. The objective of this study was to assess the potential recovery of coagulation disorders in FVIII knockout hemophilia A mice through the administration of human amniotic fluid mesenchymal stromal cells (hAFMSCs) via IUT at the D14.5 fetal stage. The findings revealed that the transplanted human cells exhibited fusion with the recipient liver, with a ratio of approximately one human cell per 10,000 mouse cells and produced human FVIII protein in the livers of IUT-treated mice. Hemophilia A pups born to IUT recipients demonstrated substantial improvement in their coagulation issues from birth throughout the growth period of up to 12 weeks of age. Moreover, FVIII activity reached its peak at 6 weeks of age, while the levels of FVIII inhibitors remained relatively low during the 12-week testing period in mice with hemophilia. In conclusion, the results indicated that prenatal intrahepatic therapy using hAFMSCs has the potential to improve clotting issues in FVIII knockout mice, suggesting it as a potential clinical treatment for individuals with hemophilia A.<\/jats:p>","DOI":"10.3390\/ijms242216411","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T07:11:27Z","timestamp":1700118687000},"page":"16411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["In Utero Cell Treatment of Hemophilia A Mice via Human Amniotic Fluid Mesenchymal Stromal Cell Engraftment"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0318-0337","authenticated-orcid":false,"given":"Yung-Tsung","family":"Kao","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan"},{"name":"Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Health Research Institutes and National Chung Hsing University, Taichung 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-7961","authenticated-orcid":false,"given":"Chih-Ching","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pulmonary Medicine Section, China Medical University Hospital, and China Medical University, Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3485-7558","authenticated-orcid":false,"given":"Hueng-Chuen","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Department of Medical Research, Tungs\u2019 Taichung Metroharbor Hospital, Wuchi, Taichung 435, Taiwan"},{"name":"Department of Rehabilitation, Jen-Teh Junior College of Medicine, Miaoli 356, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3433-5971","authenticated-orcid":false,"given":"Jen-Kun","family":"Chen","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Health Research Institutes and National Chung Hsing University, Taichung 402, Taiwan"},{"name":"Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 350, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Shan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Ditmanson Medical Foundation Chia-Yi Christion Hospital, Chia-Yi 600, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Wei","family":"Lan","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45237, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1601-3653","authenticated-orcid":false,"given":"Shang-Hsun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2461-9150","authenticated-orcid":false,"given":"Chuan-Mu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan"},{"name":"Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Health Research Institutes and National Chung Hsing University, Taichung 402, Taiwan"},{"name":"The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan"},{"name":"Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/hae.14046","article-title":"WFH Guidelines for the Management of Hemophilia, 3rd Edition","volume":"26","author":"Srivastava","year":"2020","journal-title":"Haemophilia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1111\/j.1365-2516.2012.02909.x","article-title":"Guidelines for the Management of Hemophilia","volume":"19","author":"Srivastava","year":"2013","journal-title":"Haemophilia"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Yen, C.C., Liu, Y.W., Chang, G.R.L., Lan, Y.W., Kao, Y.T., Cheng, S.N., Chen, W., and Chen, C.M. 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