Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jan 23;31(2):603-616.
doi: 10.3390/curroncol31020044.

Homing and Engraftment of Hematopoietic Stem Cells Following Transplantation: A Pre-Clinical Perspective

Tanvir Hasan  1 , Ajay Ratan Pasala  1   2 , Dhuha Hassan  1 , Justine Hanotaux  1 , David S Allan  1   2   3 , Harinad B Maganti  1   2
Affiliations
Review

Homing and Engraftment of Hematopoietic Stem Cells Following Transplantation: A Pre-Clinical Perspective

Tanvir Hasan et al. Curr Oncol. .

Abstract

Hematopoietic stem-cell (HSC) transplantation (HSCT) is used to treat various hematologic disorders. Use of genetically modified mouse models of hematopoietic cell transplantation has been critical in our fundamental understanding of HSC biology and in developing approaches for human patients. Pre-clinical studies in animal models provide insight into the journey of transplanted HSCs from infusion to engraftment in bone-marrow (BM) niches. Various signaling molecules and growth factors secreted by HSCs and the niche microenvironment play critical roles in homing and engraftment of the transplanted cells. The sustained equilibrium of these chemical and biologic factors ensures that engrafted HSCs generate healthy and durable hematopoiesis. Transplanted healthy HSCs compete with residual host cells to repopulate stem-cell niches in the marrow. Stem-cell niches, in particular, can be altered by the effects of previous treatments, aging, and the paracrine effects of leukemic cells, which create inhospitable bone-marrow niches that are unfavorable for healthy hematopoiesis. More work to understand how stem-cell niches can be restored to favor normal hematopoiesis may be key to reducing leukemic relapses following transplant.

Keywords: clonal hematopoiesis; clonal leukemogenesis; competitive repopulation; engraftment; hematopoietic stem-cell transplantation; homing; xeno-transplantation.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of clonal hematopoiesis. Somatic mutations caused as people age give certain clones of HSCs a competitive advantage over other clones, thereby leading to their taking over the hematopoietic system.
Figure 2
Figure 2
Schematic representation of competitive repopulation assay to estimate the engraftment and hematopoietic system repopulation capacity of donor vs. competitor HSCs. Donor and competitor BM cells are distinguished by unique genetic markers. Donor and competitor cells are then mixed and transplanted into lethally irradiated recipient mice. Following approximately 6 months of repopulation period, recipient BM is harvested to assess cellular composition and the contribution of donor origin vs. competitor origin, based on selected genetic markers. Figure created with BioRender.com (accessed on 15 December 2023).
See this image and copyright information in PMC

References

    1. Shultz L.D., Lyons L.B., Burzenski L.M., Gott B., Chen X., Chaleff S., Kotb M., Gillies S.D., King M., Mangada J., et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J. Immunol. 2005;174:6477–6489. doi: 10.4049/jimmunol.174.10.6477. - DOI - PubMed
    1. Ishikawa F., Yasukawa M., Lyons B., Yoshida S., Miyamoto T., Yoshimoto G., Watanabe T., Akashi K., Shultz L.D., Harada M. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chainnull mice. Blood. 2005;106:1565–1573. doi: 10.1182/blood-2005-02-0516. - DOI - PMC - PubMed
    1. Pearson T., Shultz L.D., Miller D., King M., Laning J., Fodor W., Cuthbert A., Burzenski L., Gott B., Lyons B., et al. Non-obese diabetic-recombination activating gene-1 (NOD-Rag1null) interleukin (IL)-2 receptor common gamma chain (IL2r γ null) null mice: A radioresistant model for human lymphohaematopoietic engraftment. Clin. Exp. Immunol. 2008;154:270–284. doi: 10.1111/j.1365-2249.2008.03753.x. - DOI - PMC - PubMed
    1. Hamilton N., Sabroe I., Renshaw S.A. A method for transplantation of human HSCs into zebrafish, to replace humanised murine transplantation models. F1000Research. 2018;7:594. doi: 10.12688/f1000research.14507.2. - DOI - PMC - PubMed
    1. Konantz M., Müller J.S., Lengerke C. Zebrafish Xenografts for the In Vivo Analysis of Healthy and Malignant Human Hematopoietic Cells. Methods Mol. Biol. 2019;2017:205–217. - PubMed

Publication types