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Saito, Y.* ; Ellegast, J.M.* ; Rafiei, A.* ; Song, Y.* ; Kull, D. ; Heikenwälder, M. ; Rongvaux, A.* ; Halene, S.* ; Flavell, R.A.* ; Manz, M.G.*

Peripheral blood CD34+ cells efficiently engraft human cytokine knock-in mice.

Blood 128, 1829-1833 (2016)
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Human CD34(+) hematopoietic stem and progenitor cells (HSPCs) can reconstitute a human hemato-lymphoid system when transplanted into immunocompromised mice. While fetal liver- and cord blood-derived CD34(+) cells lead to high engraftment levels, engraftment of mobilized, adult donor-derived CD34(+) cells has remained poor. We generated so-called MSTRG and MISTRG hu-manized mice on a Rag2(-/-)Il2rg(-/-) background carrying a transgene for human SIRPα and human homologues of the cytokines macrophage-colony stimulating factor, thrombopoietin, with or without interleukin-3 and granulocyte-macrophage colony stimulating factor under murine promotors. Here we transplanted mobilized peripheral blood CD34(+) cells in sub-lethally irradiated newborn and adult recipients. Human hematopoietic engraftment levels were significantly higher in bone marrow, spleen and peripheral blood in newborn transplanted MSTRG/MISTRG as compared to non-obese diabetic/severe combined immunodeficient Il2rg(-/-) or human SIRPα-transgenic Rag2(-/-)Il2rg(-/-) recipients. Furthermore newborn transplanted MSTRG/MISTRG mice supported higher engraftment levels of human phenotypically defined HSPCs in bone marrow, T-cells in the thymus, and myeloid cells in non-hematopoietic organs such as liver, lung, colon and skin, approximating the levels in the human system. Similar results were obtained in adult recipient mice. Thus, human cytokine knock-in mice might open new avenues for personalized studies of human (patho)physiology of the hematopoietic and immune system in vivo.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Hematopoietic Stem-cells; Lymphoid-system Mice; Dendritic Cells; Immune-system; Thrombopoietin; Challenges
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 128, Issue: 14, Pages: 1829-1833 Article Number: , Supplement: ,
Publisher American Society of Hematology
Publishing Place Washington
Reviewing status Peer reviewed