{"corpus_id":230779214,"paper_sha":"fbd7cae952b9ec9bedcb01fdd45a3b58fa60d50e","doi":"10.1158/1538-7445.AM2019-511","arxiv_id":null,"pmid":null,"pmcid":null,"mag_id":2953952012,"dblp_id":null,"acl_id":null,"title":"Abstract 511: An assessment of pre-conditioning regimens for optimal hCD34+ hematopoietic stem cell humanization of NSGTMmice","year":2019,"publication_date":"2019-07-01","venue":"Immunology","journal":{"name":"Immunology","pages":null,"volume":null},"journal_issn":null,"journal_title":null,"publication_types":[],"pubmed_pub_types":null,"s2_fields_of_study":["Medicine"],"reference_count":0,"citation_count":0,"influential_citation_count":0,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":null,"chemicals":null,"comments_corrections":null,"source_flags":1,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Humanized immune system (HIS) mice - immunocompromised Nod.Cg-PrkdcscidIl2rgtm1Wjl/SzJ animals in which the immune system has been humanized by the engraftment of CD34+ hematopoietic stem cells (HSC), peripheral blood mononuclear cells (PBMC), or other human cells/tissues - represent an important tool in pre-clinical oncology research. Here we investigated several pre-conditioning regimens (Busulfan pre-treatment or total body irradiation (TBI)) to determine which would yield maximum human leukocyte engraftment and lineage diversity. Animals were pre-treated either one or two doses of Busulfan (25 mg/kg) or varying doses of TBI (1.75, 2.0, or 2.5 Gy). One to two days later, animals received an adoptive transfer of native hCD34+ HSCs. Engraftment was monitored by flow cytometry assessment of peripheral blood four weeks after adoptive-transfer, and every four weeks thereafter through experiment termination at Week 16. Upon termination, spleen and bone-marrow were assessed for various leukocyte populations by flow cytometry. Animals undergoing pre-conditioning displayed increased human CD45+ cell engraftment at all timepoints as compared to animals without pre-conditioning, with animals treated with two doses of Busulfan demonstrating the greatest human CD45+ engraftment at all timepoints and reaching statistical significance at endpoint (vs no pre-conditioning; p Citation Format: Caitlin S. Parello, Benjamin G. Cuiffo, Alexandria Kury, Kasey Reardon, Brett Van Dam, Sallyann Vu, Catarina Costa, Veronica Ritchie, Gavin Gagnon, Timothy Bateson, Samantha Rogers, Gregory D. Lyng, Stephen T. Sonis. An assessment of pre-conditioning regimens for optimal hCD34+ hematopoietic stem cell humanization of NSGTMmice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 511.","claims":[{"public_id":"cl_3f5ab20e020201bc02b127865ba69161","status":"active","text":"Animals receiving pre-conditioning show increased human CD45+ cell engraftment at all measured timepoints compared to animals without pre-conditioning.","confidence":0.9,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_3f5ab20e020201bc02b127865ba69161"},{"public_id":"cl_c3cff5c91f151181c8b3357ce7092cf9","status":"active","text":"Pre-conditioning regimens using Busulfan or total body irradiation prior to adoptive transfer of native hCD34+ hematopoietic stem cells were evaluated for their effect on human leukocyte engraftment in NSG mice, with engraftment monitored by flow cytometry in peripheral blood every four weeks through week 16 and in spleen and bone marrow at study termination.","confidence":0.85,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_c3cff5c91f151181c8b3357ce7092cf9"},{"public_id":"cl_23f53023bcff667025b901f3281f54e9","status":"active","text":"Two doses of Busulfan pre-conditioning produce the greatest human CD45+ cell engraftment among the tested regimens, reaching statistical significance at study endpoint compared to no pre-conditioning.","confidence":0.88,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_23f53023bcff667025b901f3281f54e9"}],"concepts":[{"public_id":"co_219d3e32d4c177c9663f56b9c7ea4a33","status":"active","name":"human CD45+ cell engraftment","description":"The presence and level of human CD45-positive leukocytes measured in mouse blood and tissues as an indicator of humanization success.","types":["outcome measure"],"aliases":[],"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale 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