PMID- 17537129 OWN - NLM STAT- MEDLINE DCOM- 20070810 LR - 20181201 IS - 1067-1927 (Print) IS - 1524-475X (Electronic) IS - 1067-1927 (Linking) VI - 15 IP - 3 DP - 2007 May-Jun TI - Inhibition of osteogenic differentiation of human mesenchymal stem cells. PG - 413-21 AB - Mesenchymal stem cells (hMSCs) have been shown to differentiate into osteoblasts that, in turn, are capable of forming tissues analogous to bone. The present study was designed to investigate the inhibition of osteogenesis by hMSCs. Bone marrow-derived hMSCs were treated with transforming growth factor beta-3 (TGFbeta3) at various doses during or after their differentiation into osteogenic cells. TGFbeta3 was encapsulated in poly(DL-lactic-co-glycolic acid) (PLGA) microspheres and released via controlled delivery in the osteogenic culture of hMSCs and hMSC-derived osteoblasts for up to 28 days. Controlled release of TGFbeta3 inhibited the osteogenic differentiation of hMSCs, as evidenced by significantly reduced alkaline phosphatase activity and staining, as well as decreased mineral deposition. After hMSCs had been differentiated into osteoblasts, controlled release of TGFbeta3 further inhibited not only alkaline phosphatase and mineral deposition but also osteocalcin expression. These findings demonstrate the potential for sustained modulation of the behavior of stem cells and/or stem cell-derived lineage-specific cells via controlled release of growth factor(s). The attenuation of osteogenic differentiation of MSCs may facilitate understanding not only the regulation and patterning of osteogenesis in development but also several pathological models such as osteopetrosis, craniosynostosis, and heart valve calcification. FAU - Moioli, Eduardo K AU - Moioli EK AD - Department of Biomedical Engineering, College of Dental Medicine, Columbia University, Fu Foundation School of Engineering and Applied Sciences, New York, New York 10032, USA. FAU - Hong, Liu AU - Hong L FAU - Mao, Jeremy J AU - Mao JJ LA - eng GR - RC2 DE020767-02/DE/NIDCR NIH HHS/United States GR - DE15391/DE/NIDCR NIH HHS/United States GR - RC2 DE020767/DE/NIDCR NIH HHS/United States GR - R01 EB002332/EB/NIBIB NIH HHS/United States GR - R01 DE015391/DE/NIDCR NIH HHS/United States GR - EB02332/EB/NIBIB NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Wound Repair Regen JT - Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society JID - 9310939 RN - 0 (Delayed-Action Preparations) RN - 0 (Transforming Growth Factor beta3) RN - 26009-03-0 (Polyglycolic Acid) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Alkaline Phosphatase/metabolism MH - Cell Differentiation/drug effects MH - Cells, Cultured MH - Delayed-Action Preparations MH - Humans MH - Kinetics MH - *Mesenchymal Stem Cells/cytology/drug effects/enzymology MH - Microspheres MH - Osteoblasts/drug effects MH - Osteogenesis/*drug effects MH - Polyglycolic Acid MH - Transforming Growth Factor beta3/administration & dosage/*pharmacology PMC - PMC4035040 MID - NIHMS232011 EDAT- 2007/06/01 09:00 MHDA- 2007/08/11 09:00 PMCR- 2014/05/27 CRDT- 2007/06/01 09:00 PHST- 2007/06/01 09:00 [pubmed] PHST- 2007/08/11 09:00 [medline] PHST- 2007/06/01 09:00 [entrez] PHST- 2014/05/27 00:00 [pmc-release] AID - WRR244 [pii] AID - 10.1111/j.1524-475X.2007.00244.x [doi] PST - ppublish SO - Wound Repair Regen. 2007 May-Jun;15(3):413-21. doi: 10.1111/j.1524-475X.2007.00244.x.