{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:34:49Z","timestamp":1787841289784,"version":"build-2784847793"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,4,19]],"date-time":"2016-04-19T00:00:00Z","timestamp":1461024000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Hemophilia A is an X-linked rescessive bleeding disorder that results from\n                      <jats:italic toggle=\"yes\">F8<\/jats:italic>\n                      gene aberrations. Previously, we established embryonic stem (ES) cells (tet-226aa\/N6-Ainv18) that secrete human factor VIII (hFVIII) by introducing the human\n                      <jats:italic toggle=\"yes\">F8<\/jats:italic>\n                      gene in mouse Ainv18 ES cells. Here, we explored the potential of cell transplantation therapy for hemophilia A using the ES cells. Transplant tet-226aa\/N6-Ainv18 ES cells were injected into the spleens of severe combined immunodeficiency (SCID) mice, carbon tetrachloride (CCl\n                      <jats:sub>4<\/jats:sub>\n                      )-pretreated wild-type mice, and CCl\n                      <jats:sub>4<\/jats:sub>\n                      -pretreated hemophilia A mice.\n                      <jats:italic toggle=\"yes\">F8<\/jats:italic>\n                      expression was induced by doxycycline in drinking water, and hFVIII-antigen production was assessed in all cell transplantation experiments. Injecting the ES cells into SCID mice resulted in an enhanced expression of the hFVIII antigen; however, teratoma generation was confirmed in the spleen. Transplantation of ES cells into wild-type mice after CCl4-induced liver injury facilitated survival and engraftment of transplanted cells without teratoma formation, resulting in hFVIII production in the plasma. Although CCl\n                      <jats:sup>4<\/jats:sup>\n                      was lethal to most hemophilia A mice, therapeutic levels of FVIII activity, as well as the hFVIII antigen, were detected in surviving hemophilia A mice after cell transplantation. Immunolocalization results for hFVIII suggested that transplanted ES cells might be engrafted at the periportal area in the liver. Although the development of a safer induction method for liver regeneration is required, our results suggested the potential for developing an effective ES-cell transplantation therapeutic model for treating hemophilia A in the future.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.hemonc.2016.04.002","type":"journal-article","created":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T19:51:37Z","timestamp":1461959497000},"page":"64-70","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Therapeutic approaches for treating hemophilia A using embryonic stem cells"],"prefix":"10.4103","volume":"9","author":[{"given":"Shogo","family":"Kasuda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Tatsumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Shima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Hatake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1016\/j.hemonc.2016.04.002_b0005","first-page":"292","article-title":"Plasma-derived versus recombinant factor VIII concentrates for the treatment of haemophilia A: recombinant is better","volume":"8","author":"Franchini","year":"2010","journal-title":"Blood 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