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Experimental Models of Mouse and Human Hematopoietic Stem Cell Transplantation

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Hematopoietic Stem Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2567))

Abstract

Experimental hematopoietic stem cell transplantation (HSCT) is an invaluable tool in determining the function and characteristics of hematopoietic stem cells (HSC) from experimental mouse and human donor groups. These groups could include, but are not limited to, genetically altered populations (gene knockout/knockin models), ex vivo manipulated cell populations, or in vivo modulated cell populations. The basic fundamentals of this process involve taking cells from a mouse/human donor source and putting them into another mouse (recipient) after preconditioning of the recipient with either total body irradiation (TBI) for mouse donor cells or into sublethally irradiated immune-deficient mice for human donor cells. Then, at pre-determined time points post-transplant, sampling a small amount of peripheral blood (PB) and at the termination of the evalaution, bone marrow (BM) to determine donor contribution and function by phenotypic analysis. Exploiting the congenic mouse strains of C57BL/6 (CD45.1− CD45.2+), BoyJ (CD45.1+ CD45.2−), and their F1-crossed hybrid C57BL/6 × BoyJ (CD45.1+ CD45.2+), we are able to quantify donor, competitor, and recipient mouse cell contributions to the engraftment state. Human donor cell engraftment (e.g., from the cord blood [CB], mobilized PB, or BM) is assessed by human cell phenoty** in sublethally irradiated immune-deficient mouse recipients (e.g., NOD scid gamma mice that are deficient in B cells, T cells, and natural killer cells and have defective dendritic cells and macrophages). Engraftment of cells from primary mouse recipients into secondary mice allows for an estimation of the self-renewal capacity of the original donor HSC. This chapter outlines concepts, methods, and techniques for mouse and human cell models of HSCT and for assessment of donor cells collected and processed in hypoxia versus ambient air.

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Authors and Affiliations

  1. Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN, USA

    Scott H. Cooper, Maegan L. Capitano & Hal E. Broxmeyer

Authors
  1. Scott H. Cooper
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  2. Maegan L. Capitano
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  3. Hal E. Broxmeyer
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Corresponding author

Correspondence to Scott H. Cooper .

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Editors and Affiliations

  1. Department of Microbiology & Immunology and Department of Medicine/Hematology Oncology, Indiana University School of Medicine, Indianapolis, IN, USA

    Louis M. Pelus

  2. Moderna Therapeutics, Cambridge, MA, USA

    Jonathan Hoggatt

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Cooper, S.H., Capitano, M.L., Broxmeyer, H.E. (2023). Experimental Models of Mouse and Human Hematopoietic Stem Cell Transplantation. In: Pelus, L.M., Hoggatt, J. (eds) Hematopoietic Stem Cells. Methods in Molecular Biology, vol 2567. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2679-5_14

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  • DOI: https://doi.org/10.1007/978-1-0716-2679-5_14

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2678-8

  • Online ISBN: 978-1-0716-2679-5

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