Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone
Open accessAbstract
Treatment with isolated allogeneic mesenchymal cells has the potential to enhance the therapeutic effects of conventional bone marrow transplantation in patients with genetic disorders affecting mesenchymal tissues, including bone, cartilage, and muscle. To demonstrate the feasibility of mesenchymal cell therapy and to gain insight into the transplant biology of these cells, we used gene-marked, donor marrow-derived mesenchymal cells to treat six children who had undergone standard bone marrow transplantation for severe osteogenesis imperfecta. Each child received two infusions of the allogeneic cells. Five of six patients showed engraftment in one or more sites, including bone, skin, and marrow stroma, and had an acceleration of growth velocity during the first 6 mo postinfusion. This improvement ranged from 60% to 94% (median, 70%) of the predicted median values for age- and sex-matched unaffected children, compared with 0% to 40% (median, 20%) over the 6 mo immediately preceding the infusions. There was no clinically significant toxicity except for an urticarial rash in one patient just after the second infusion. Failure to detect engraftment of cells expressing the neomycin phosphotransferase marker gene suggested the potential for immune attack against therapeutic cells expressing a foreign protein. Thus, allogeneic mesenchymal cells offer feasible posttransplantation therapy for osteogenesis imperfecta and likely other disorders originating in mesenchymal precursors.
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Clinical applications involving systemic administration of MSCs require a large number of cells (1-10 × 106 cells/kg) to demonstrate therapeutic efficacy.
“Clinical applications involving systemic administration of MSCs require a large number of cells (1–10 × 106 cells/kg) to demonstrate a therapeutic efficacy [27–29].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [27]
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- Authors
- Horwitz, E. M., Gordon, P. L., Koo, W. K. K., Marx, J. C., Neel, M. D., McNall, R. Y., Muul, L., & Hofmann, T.
- Affiliations
- National Institutes of Health (US)
- Transplantation and Gene Therapy Program, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105; Wayne State University, 4707 St. Antoine Boulevard, Detroit, MI 48201; and Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-06-25
- Volume
- 99
- Issue
- 13
- Pages
- 8932-8937
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC124401
- OpenAlex
- W2061981400
- Cited by
- 1,650
- References
- 38
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 27 · 2023: 34 · 2022: 33 · 2021: 32 · 2020: 42 · 2019: 64 · 2018: 54 · 2017: 55 · 2016: 73 · 2015: 79 · 2014: 110 · 2013: 131 · 2012: 122
- FWCI
- 20.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Doris Duke Charitable Foundation
- American Lebanese Syrian Associated Charities (CA 21765)
- National Cancer Institute (CA21765, 21765, P30CA021765)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Keywords
- osteogenesis imperfecta, cell therapy, cell engraftment, bone marrow transplantation, growth rate, children
- MeSH terms
- Base Sequence, Cell Division, Child, Preschool, Female, Humans, Male, Osteogenesis Imperfecta, Transplantation, Homologous, Absorptiometry, Photon, Bone Marrow Transplantation, DNA Primers
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