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Some outstanding challenges in the HSCT field include the paucity of immunologically-matched donors, our inability to effectively expand hematopoeitic stem cells (HSCs) ex vivo, and the high infection risk during engraftment. Scientists are striving to develop protocols to generate, expand, and maintain HSCs ex vivo, however these are not yet ready for clinical application. Given these problems, advancing our understanding of HSC specification, regulation, and differentiation in preclinical models is essential to improve the therapeutic utility of HSCT. In this review, we link biomedical researchers and transplantation clinicians by discussing the potential therapeutic implications of recent fundamental HSC research in model organisms. We consider deficiencies in current HSCT practice, such as problems achieving adequate cell dose for successful and rapid engraftment, immense inflammatory cascade activation after myeloablation, and graft-vs-host disease. Furthermore, we discuss recent advances in the field of HSC biology and transplantation made in preclinical models of zebrafish, mouse, and nonhuman primates that could inform emerging practice for clinical application.<\/jats:p>","DOI":"10.1002\/sctm.20-0294","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T10:48:56Z","timestamp":1602758936000},"page":"337-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Advances in preclinical hematopoietic stem cell models and possible implications for improving therapeutic transplantation"],"prefix":"10.1093","volume":"10","author":[{"given":"Ellen","family":"Fraint","sequence":"first","affiliation":[{"name":"Department of Pediatrics Children's Hospital at Montefiore, Bronx, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca A.","family":"Ulloa","sequence":"additional","affiliation":[{"name":"Department of Developmental and Molecular Biology Albert Einstein College of Medicine, Bronx, New York, USA"},{"name":"Gottesman Institute for Stem Cell Biology and Regenerative Medicine Albert Einstein College of Medicine, Bronx, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Feliz Norberto","sequence":"additional","affiliation":[{"name":"Department of Developmental and Molecular Biology Albert Einstein College of Medicine, Bronx, New York, USA"},{"name":"Gottesman Institute for Stem Cell Biology and Regenerative Medicine Albert Einstein College of Medicine, Bronx, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn S.","family":"Potts","sequence":"additional","affiliation":[{"name":"Department of Developmental and Molecular Biology Albert Einstein College of Medicine, Bronx, New York, USA"},{"name":"Gottesman Institute for Stem 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