Non-hematopoietic human bone marrow contains long-lasting, pluripotential mesenchymal stem cells
Article first published online: 3 SEP 2003
Copyright © 2003 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 198, Issue 1, pages 110–118, January 2004
How to Cite
Suva, D., Garavaglia, G., Menetrey, J., Chapuis, B., Hoffmeyer, P., Bernheim, L. and Kindler, V. (2004), Non-hematopoietic human bone marrow contains long-lasting, pluripotential mesenchymal stem cells. J. Cell. Physiol., 198: 110–118. doi: 10.1002/jcp.10396
- Issue published online: 20 OCT 2003
- Article first published online: 3 SEP 2003
- Manuscript Accepted: 6 JUN 2003
- Manuscript Received: 12 MAY 2003
- Fonds National Suisse pour la Recherche Scientifique. Grant Numbers: 3165409.01, 4046-058639
- Fondation Suisse pour la Recherche sur les Maladies Musculaires
Mesenchymal stem cells (MSC) are considered as potential agents for reconstructive and gene-targeting therapies since they differentiate into various cell-lineages, exhibit an extended survival once injected into a host, and can easily be transfected with engineered DNA. MSC are essentially isolated from hematopoietic bone marrow (BM), a process that is rather invasive and may raise ethical concerns. In an attempt to find an alternative source, we evaluated whether non-hematopoietic (nh)BM recovered from femoral heads of patients undergoing hip arthroplasty contained MSC. Ex vivo, 99% of nhBM cells were CD45+ leukocytes. After culture, leukocytes were replaced by a homogenous layer of adherent CD45− CD14− CD34− CD11b− CD90+ HLA-ABC+ cells. Culture doubling time (mean = 4 days, range 1.6–6.7 days) was not correlated with patient age (27–81 years, n = 16). Amplified cultures supported long-term hematopoiesis, and could be differentiated in vitro into adipocytes and chondrocytes. Moreover, a small fraction of nhBM cells spontaneously expressed MyoD1 and formed myotubes, suggesting that myogenic differentiation also occurred. nhBM contained clonogenic cells whose frequency (1/13,000), doubling time (2.1 days), and maximal amplification (up to 106-fold) were not age-related. All 14 clones analyzed (from five patients, ages 27–78 years) differentiated into at least one mesenchymal lineage, and 66% were bipotential (n = 8/12), or tripotential (n = 2/3). In conclusion, nhBM contains pluripotential mesenchymal progenitors which are similar to hematopoietic BM-derived MSC, and whose biological functions are not altered by aging. Furthermore, if MSC-based therapies hold their promises, nhBM may become the source of choice for responding to the increasing demand for MSC. J. Cell. Physiol. 198: 110–118, 2004. © 2003 Wiley-Liss, Inc.