{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:56:55Z","timestamp":1789851415282,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2007,9,17]],"date-time":"2007-09-17T00:00:00Z","timestamp":1189987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hemophilia B is a bleeding disorder caused by defective factor IX (FIX), currently treated by regular infusions of plasma\u2010derived or recombinant FIX. We propose a gene therapy strategy based on the implantation of cells secreting FIX enclosed in alginate microcapsules as a highly desirable alternative treatment. We have reported sustained delivery of human factor IX (hFIX) in immunocompetent mice implanted with encapsulated primary mouse myoblasts engineered to secrete hFIX. As a step towards the treatment of human patients, in this study we report the implantation of encapsulated human primary myoblasts secreting hFIX in hemophilia B mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human primary myoblasts were transfected with plasmids pKL4M\u2010hFIX, pLNM\u2010\u03b2IXL, pMFG\u2010hFIX, and transduced with retrovirus MFG\u2010hFIX. Two human primary myoblast clones secreting \u223c1 \u00b5g hFIX\/10<jats:sup>6<\/jats:sup> cells\/day were enclosed in biocompatible alginate microcapsules and implanted intraperitoneally into SCID and hemophilic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Circulating hFIX (peak of \u223c120 ng\/ml) was detected in hemophilia B mice on day 1 after implantation. Human FIX delivery was transient, however, becoming undetectable on day 14. Concurrently, anti\u2010hFIX antibodies were detected. At the same time, activated partial thromboplastin time (APTT) was reduced from 94 s before treatment to 78\u201380 s. Tail bleeding time decreased from 15 min to 1.5\u20137 min after treatment, some mice being normalised. These findings indicate that the delivered hFIX is biologically active. Similarly treated NOD\/SCID mice had circulating hFIX levels of 170 ng\/ml on day 1 that remained detectable for 1 month, albeit at low levels. Cell viability of microcapsules retrieved on day 60 was below 5%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings indicate that encapsulated human primary myoblasts secrete functional hFIX. Furthermore, implantation of encapsulated human primary myoblasts can partially correct the phenotype of hemophilia B mice, supporting the feasibility of this gene therapy approach for hemophilia B. However, the long\u2010term viability of the encapsulated human myoblasts must first be improved. Copyright \u00a9 2007 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.1098","type":"journal-article","created":{"date-parts":[[2007,9,17]],"date-time":"2007-09-17T10:17:29Z","timestamp":1190024249000},"page":"1002-1010","source":"Crossref","is-referenced-by-count":17,"title":["Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice"],"prefix":"10.1002","volume":"9","author":[{"given":"Jianping","family":"Wen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Bourgeois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick A.","family":"Ofosu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Hortelano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,9,17]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"575","volume-title":"The Molecular Basis of Blood Diseases","author":"Sadler JE","year":"1987"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.2165\/00063030-200418040-00002"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0268-960X(03)00038-9"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-825637"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2003.00725.x"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3296"},{"key":"e_1_2_6_8_2","volume-title":"Cell Transplants: from Laboratory to Clinic","author":"Gomez\u2010Vargas A","year":"2006"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200106073442301"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0103-104"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2003.11.004"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2006.03.014"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-005-0687-3"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.12.5095.bloodjournal87125095"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/4751"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.04.010"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2001.00492.x"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.852"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.8.3357"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01233861"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1159\/000016776"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02721371"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.21.11563"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-825638"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-825639"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088547"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1358"},{"key":"e_1_2_6_28_2","first-page":"119","article-title":"Myoblast transplantation: clinical trials and perspectives","volume":"24","author":"Vilquin JT","year":"2005","journal-title":"Acta Myol"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio0399"},{"key":"e_1_2_6_30_2","first-page":"128","article-title":"Myoblast transfer therapy: is there any light at the end of the tunnel?","volume":"24","author":"Mouly V","year":"2005","journal-title":"Acta Myol"},{"key":"e_1_2_6_31_2","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.1182\/blood.V95.10.3102","article-title":"Beta 2 microglobulin\u2010deficient (B2m(null)) NOD\/SCID mice are excellent recipients for studying human stem cell function","volume":"95","author":"Kollet O","year":"2000","journal-title":"Blood"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1163\/15685620360674236"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1159\/000086228"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10265"}],"container-title":["The Journal of Gene Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjgm.1098","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgm.1098","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T15:26:00Z","timestamp":1700061960000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jgm.1098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9,17]]},"references-count":33,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2007,11]]}},"alternative-id":["10.1002\/jgm.1098"],"URL":"https:\/\/doi.org\/10.1002\/jgm.1098","archive":["Portico"],"relation":{},"ISSN":["1099-498X","1521-2254"],"issn-type":[{"value":"1099-498X","type":"print"},{"value":"1521-2254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,9,17]]}}}