Arthritis Research & Therapy · 2000 · 747 citations · 39 references
Life SciencesCell BiologyDevelopmental BiologyBone MetabolismRegenerative MedicineStem Cell BiologyBone DevelopmentBone FormationBone Morphogenetic Protein SignalingBone RegenerationBone TissueMesenchymal DifferentiationBmp ReceptorsBone Marrow-derived Mesenchymal Stromal CellsBone Morphogenetic Protein ReceptorsGrowth FactorsOsteogenic DifferentiationOsteogenic MarkersStromal TissueTartrate-resistant Acid Phosphatase Activity
Mesenchymal precursor cells in normal blood adhere to plastic and glass and proliferate logarithmically in DMEM‑20% fetal calf serum without added growth factors. When cultured with osteogenic supplements, these cells differentiate into osteoblast‑like cells that express alkaline phosphatase (enhanced by BMP‑2), with 30 % becoming osteocalcin‑positive after two weeks, while the cultures also generate adipocytes, multinucleated giant cells, and express mesenchymal markers such as vimentin, type I collagen, BMP receptors, and CD105.
Mesenchymal precursor cells found in the blood (BMPCs) of normal persons adhere to plastic and glass and proliferate logarithmically in DMEM-20% fetal calf serum (FCS) without growth factors. They form cells with fibroblast-like and stromal morphology, which is not affected by eliminating CD34, CD3, or CD14 cells. Osteogenic supplements (dexamethasone, ascorbic acid, and β-glycerophosphate) added to the culture inhibited fibroblast formation, and BMPCs assumed the cuboidal shape of osteoblasts. After 5 days in supplemented medium, the elutriated cells displayed alkaline phosphatase (AP), and the addition of bone morphogenetic protein (BMP)2 (1 ng) doubled AP production (P < 0.04). Two weeks later, 30% of the cells were very large and reacted with anti-osteocalcin antibody. The same cultures also contained sudanophlic adipocytes and multinucleated giant cells that stained for tartrate-resistant acid phosphatase (TRAP) and vitronectin receptors. Cultured BMPCs immunostain with antibodies to vimentin, type I collagen, and BMP receptors, heterodimeric structures expressed on mesenchymal lineage cells. In addition, BMPCs stain with anti-CD105 (endoglin), a putative marker for bone-marrow mesenchymal stem cells (MSCs).
39
Multilineage Potential of Adult Human Mesenchymal Stem Cells
Mark F. Pittenger, Alastair M. Mackay, Stephen C. Beck et al. · Science · 1999 · 21.1K citations
Isolation of Putative Progenitor Endothelial Cells for Angiogenesis
Takayuki Asahara, Toyoaki Murohara, Alison Sullivan et al. · Science · 1997 · 8.7K citations
Arnold I. Caplan · Journal of Orthopaedic Research® · 1991 · 6.5K citations
Muscle Regeneration by Bone Marrow-Derived Myogenic Progenitors
Giuliana Ferrari, Maria Gabriella Cusella De Angelis, De Angelis et al. · Science · 1998 · 2.7K citations · Full text