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Recently, a strain of immunodeficient pigs (termed RGD pigs) was developed through the genetic inactivation of\n                    <jats:italic>RAG1<\/jats:italic>\n                    ,\n                    <jats:italic>IL2RG<\/jats:italic>\n                    , and\n                    <jats:italic>CD47<\/jats:italic>\n                    . These RGD pigs lack functional T, B, and NK cells and do not exhibit CD47\u2010SIRP\u03b1 incompatibility\u2010triggered macrophage xenoresponses. Transplantation of human hematopoietic stem\/progenitor cells (HSPCs) into RGD pigs results in high levels of durable human hematopoietic engraftment and systemic repopulation with multilineage human lymphohematopoietic cells, including T, B, NK, and myeloid cells. The transplanted pigs maintain robust human hematopoiesis in the bone marrow (BM) and ongoing thymopoiesis in the thymus. Human T and B cells developing in these pigs express broad antigen receptor repertoires and exhibit tolerance to the recipient pig. The RGD pig is considered a valuable preclinical model for investigating normal or diseased human hematopoiesis and related therapies, and offers a potential bioreactor for large\u2010scale production of human immune cells. These pigs are also highly valuable for in vivo studies on other types of human tissues and cells.\n                  <\/jats:p>","DOI":"10.1111\/xen.70077","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T12:25:45Z","timestamp":1757939145000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Human Hematopoietic Stem Cell Engraftment and Differentiation in Immunodeficient Pigs"],"prefix":"10.1111","volume":"32","author":[{"given":"Chen\u2010Chen","family":"Pi","sequence":"first","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education The First Hospital of Jilin University  Changchun China"},{"name":"National\u2010local Joint Engineering Laboratory of Animal Models For Human Diseases Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education The First Hospital of Jilin University  Changchun China"},{"name":"National\u2010local Joint Engineering Laboratory of Animal Models For Human Diseases Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghui","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education The First Hospital of Jilin University  Changchun China"},{"name":"National\u2010local Joint Engineering Laboratory of Animal Models For Human Diseases Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education The First Hospital of Jilin University  Changchun China"},{"name":"National\u2010local Joint Engineering Laboratory of Animal Models For Human Diseases Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong\u2010Guang","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education The First Hospital of Jilin University  Changchun China"},{"name":"National\u2010local Joint Engineering Laboratory of Animal Models For Human Diseases Jilin University  Changchun China"},{"name":"International Center of Future Science Jilin University  Changchun Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1296-1329"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/367645a0"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139851"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.1.180"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.10.6477"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200001150-00027"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702881104"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609661104"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2099"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1527"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2858"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-301507"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093933"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-02-0516"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-10-3697"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4388"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1431"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.034"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710415114"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0225-9"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100122"},{"issue":"2","key":"e_1_2_11_23_1","first-page":"39","article-title":"Immune\u2010Deficient Mice as Models of Normal and Leukemic Human Hematopoiesis","volume":"3","author":"Dick J. 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