Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion
Open accessAbstract
Strategies for expanding hematopoietic stem cells (HSCs) include coculture with cells that recapitulate their natural microenvironment, such as bone marrow stromal stem/progenitor cells (BMSCs). Plastic-adherent BMSCs may be insufficient to preserve primitive HSCs. Here, we describe a method of isolating and culturing human BMSCs as nonadherent mesenchymal spheres. Human mesenspheres were derived from CD45- CD31- CD71- CD146+ CD105+ nestin+ cells but could also be simply grown from fetal and adult BM CD45--enriched cells. Human mesenspheres robustly differentiated into mesenchymal lineages. In culture conditions where they displayed a relatively undifferentiated phenotype, with decreased adherence to plastic and increased self-renewal, they promoted enhanced expansion of cord blood CD34+ cells through secreted soluble factors. Expanded HSCs were serially transplantable in immunodeficient mice and significantly increased long-term human hematopoietic engraftment. These results pave the way for culture techniques that preserve the self-renewal of human BMSCs and their ability to support functional HSCs.
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HSCs lose function when maintained ex vivo, even in the presence of niche cells that sustain HSC potency in vivo.
“HSCs lose function when maintained ex vivo, even in the presence of niche cells that sustain HSC potency in vivo234.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [234]
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References 48 · Cited by 141
- Authors
- Isern, J., Martín-Antonio, B., Ghazanfari, R., Martín, A. M., López, J. A., del Toro, R., Sánchez-Aguilera, A., Arranz, L., Martín-Pérez, D., Suárez-Lledó, M., Marín, P., Van Pel, M., Fibbe, W. E., Vázquez, J., Scheding, S., Urbano-Ispizúa, Á., & Méndez-Ferrer, S.
- Affiliations
- Spanish National Centre for Cardiovascular Research (ES)
- Hospital Clínic de Barcelona (ES)
- Lund University (SE)
- Leiden University Medical Center (NL)
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 3
- Issue
- 5
- Pages
- 1714-1724
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2168357515
- Cited by
- 141
- References
- 48
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 14 · 2021: 8 · 2020: 17 · 2019: 10 · 2018: 13 · 2017: 7 · 2016: 19 · 2015: 12 · 2014: 13 · 2013: 9
- FWCI
- 12.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion, cc-by)
- Funders
- Centro Nacional de Investigaciones Cardiovasculares
- Swedish Cancer Foundation
- Barncancerfonden
- Marie Curie (FP7-PEOPLE-2011-RG-294096, FP7-PEOPLE-2011-RG-294262)
- Consejería de Salud y Familias, Junta de Andalucía (PI0079)
- Ministerio de Educación, Cultura y Deporte
- Ministerio de Economía y Competitividad (BIO2009-07990, RYC-2009-04703, RYC-2011-09209, RYC-2011-09726, SAF2011-30308)
- Vetenskapsrådet
- Howard Hughes Medical Institute
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- hematopoietic stem cell expansion, bone marrow mesenchymal stem cells, self-renewal, cord blood CD34+ cells, soluble factors, hematopoietic engraftment, stem cell niche, mesenchymal differentiation, serial transplantation
- MeSH terms
- Animals, Bone Marrow Cells, Cell Differentiation, Cells, Cultured, Fetal Blood, Hematopoietic Stem Cells, Humans, Antigens, CD, Mice, Inbred NOD, Coculture Techniques, Cell Lineage, Mice, Mesenchymal Stem Cells, Nestin
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