Mesenchymal stem cells secreting angiopoietin-like-5 support efficient expansion of human hematopoietic stem cells without compromising their repopulating potential
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Author(s)
Drake, Adam
Chen, Qingfeng
Dong, Di
Leskov, Ilya B.
Fragoso, Maria F.
Li, Yan
Iliopoulou, Bettina P.
Hwang, William
Lodish, Harvey F.
Chen, Jianzhu
Date Issued
December 2010
Journal
Stem Cells and Development
Publisher
Mary Ann Liebert
Citation
Khoury, Maroun et al. “Mesenchymal Stem Cells Secreting Angiopoietin-Like-5 Support Efficient Expansion of Human Hematopoietic Stem Cells Without Compromising Their Repopulating Potential.” Stem Cells and Development 20.8 (2011): 1371–1381. Copyright © 2011 Mary Ann Liebert, Inc. publishers.
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Final published version
Abstract
Clinical and preclinical applications of human hematopoietic stem cells (HSCs) are often limited by scarcity of cells. Expanding human HSCs to increase their numbers while maintaining their stem cell properties has therefore become an important area of research. Here, we report a robust HSC coculture system wherein cord blood CD34+ CD133+ cells were cocultured with mesenchymal stem cells engineered to express angiopoietin-like-5 in a defined medium. After 11 days of culture, SCID repopulating cells were expanded 60-fold by limiting dilution assay in NOD-scid Il2rg−/− (NSG) mice. The cultured CD34+ CD133+ cells had similar engraftment potential to uncultured CD34+ CD133+ cells in competitive repopulation assays and were capable of efficient secondary reconstitution. Further, the expanded cells supported a robust multilineage reconstitution of human blood cells in NSG recipient mice, including a more efficient T-cell reconstitution. These results demonstrate that the expanded CD34+ CD133+ cells maintain both short-term and long-term HSC activities. To our knowledge, this 60-fold expansion of SCID repopulating cells is the best expansion of human HSCs reported to date. Further development of this coculture method for expanding human HSCs for clinical and preclinical applications is therefore warranted.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1089/scd.2010.0456
