title: Replicative senescence of human bone marrow and umbilical cord derived mesenchymal stem cells and their differentiation to adipocytes and osteoblasts.
abstract: Mesenchymal stem cells (MSC) which have self-renewal and multiple differentiation potential in vitro play important roles in regenerative medicine and tissue engineering. However, long-term culture in vitro leads to senescence which results in the growth arrest and reduction of differentiation. In this study, MSC derived from human bone-marrow (BM-MSC) and umbilical cord (UC-MSC) were cultured in vitro lasted to senescence. Senescence and apoptosis detection showed that the senescent cells increased significantly but the increase of apoptosis was not significant in the long term culture. Senescence related genes p16, p21 and p53 increased gradually in BM-MSC. However, p16 and p53 reduced and then increased but with the gradual increase of p21 in UC-MSC. Adipogenic differentiation decreased whereas the propensity for osteogenic differentiation increased in senescent MSC. Real time RT-PCR demonstrated that both C/EBPα and PPARγ decreased in senescent BM-MSC. However, in UC-MSC, PPARγ decreased but C/EBPα increased in late phase compared to early phase. The study demonstrated p21 was important in the senescence of BM-MSC and UC-MSC. C/EBPα and PPARγ could regulate the balance of adipogenic differentiation in BM-MSC but only PPARγ not C/EBPα was involved in the adipogenic differentiation in UC-MSC.
authors.affiliation: Institute of Harbin Hematology & Oncology, Harbin First Hospital, Number 149 of Diduan Street, 150010 Harbin, People's Republic of China.
authors.forename: Huanchen
authors.initials: H
authors.lastname: Cheng
authors.forename: Lin
authors.initials: L
authors.lastname: Qiu
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Cheng
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xuefei
authors.initials: X
authors.lastname: Zhao
authors.forename: Keyu
authors.initials: K
authors.lastname: Liu
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D048430:Cell Shape; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology*; D055815:Young Adult
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047495:PPAR gamma; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D000469:Alkaline Phosphatase