Dependence of Human Stem Cell Engraftment and Repopulation of NOD/SCID Mice on CXCR4
Abstract
Stem cell homing and repopulation are not well understood. The chemokine stromal cell–derived factor-1 (SDF-1) and its receptor CXCR4 were found to be critical for murine bone marrow engraftment by human severe combined immunodeficient (SCID) repopulating stem cells. Treatment of human cells with antibodies to CXCR4 prevented engraftment. In vitro CXCR4-dependent migration to SDF-1 of CD34 + CD38 −/low cells correlated with in vivo engraftment and stem cell function. Stem cell factor and interleukin-6 induced CXCR4 expression on CD34 + cells, which potentiated migration to SDF-1 and engraftment in primary and secondary transplanted mice. Thus, up-regulation of CXCR4 expression may be useful for improving engraftment of repopulating stem cells in clinical transplantation.
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- Authors
- Peled, A., Petit, I., Kollet, O., Magid, M., Ponomaryov, T., Byk, T., Nagler, A., Ben-Hur, H., Many, A., Shultz, L., Lider, O., Alon, R., Zipori, D., & Lapidot, T.
- Affiliations
- Department of Immunology and
- Weizmann Institute of Science (IL)
- Hadassah Medical Center (IL)
- Kaplan Medical Center, Rehovot 76100, Israel.
- Tel Aviv Sourasky Medical Center (IL)
- Jackson Laboratory (US)
- Corresponding author
- Lapidot, Tsvee
- Venue
- Science
- Published
- 1999-02-05
- Volume
- 283
- Issue
- 5403
- Pages
- 845-848
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2141837666
- Cited by
- 1,644
- References
- 0
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 6 · 2023: 39 · 2022: 25 · 2021: 32 · 2020: 35 · 2019: 39 · 2018: 38 · 2017: 55 · 2016: 51 · 2015: 51 · 2014: 76 · 2013: 72 · 2012: 59
- FWCI
- 40.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- U.S. Public Health Service (A130 389)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- CXCR4, CXCL12, stem cell homing, stem cell engraftment, hematopoietic repopulation, NOD/SCID mice, CD34+ cells, chemokine receptors, stem cell migration, stem cell factor, interleukin-6, bone marrow transplantation, human stem cells
- MeSH terms
- Animals, Antibodies, Antigens, Differentiation, Chemotaxis, Colony-Forming Units Assay, Fetal Blood, Hematopoietic Stem Cells, Humans, Membrane Glycoproteins, NAD+ Nucleosidase, Tetradecanoylphorbol Acetate, Antigens, CD, Interleukin-6, Up-Regulation, Mice, SCID, Mice, Inbred NOD, Mice, Knockout, Hematopoietic Stem Cell Transplantation, Antigens, CD34, Stem Cell Factor, Hematopoietic Stem Cell Mobilization, Receptors, CXCR4, Chemokines, CXC, ADP-ribosyl Cyclase, Mice, ADP-ribosyl Cyclase 1, Chemokine CXCL12
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