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Title

Non-hematopoietic human bone marrow contains long-lasting, pluripotential mesenchymal stem cells

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Published in Journal of Cellular Physiology. 2004, vol. 198, no. 1, p. 110-118
Abstract 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 homogeneous 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 10(6)-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.
Keywords Adipocytes/cytology/metabolismAdultAgedAged, 80 and overAntigens, CD45/metabolismBone Marrow Cells/cytology/ metabolismCell Differentiation/physiologyCell DivisionCells, CulturedChondrocytes/cytology/metabolismFemur/cytology/metabolismHematopoiesis/ physiologyHumansMesoderm/ cytology/metabolismMiddle AgedMyoblasts/metabolismPhenotypePluripotent Stem Cells/cytology/ physiology
Stable URL http://archive-ouverte.unige.ch/unige:10454
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PMID: 14584050
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Research groups Thérapie cellulaire et troubles musculo-squelettiques (960)
Culture Primaire de myoblastes humains (208)
Immunité innée non leucocytaire (928)
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