title: Improved osteogenesis and upregulated immunogenicity in human placenta-derived mesenchymal stem cells primed with osteogenic induction medium.
abstract: Mesenchymal stem cells (MSCs) are widely used in cell-based therapy owing to their multilineage potential and low immunogenicity. However, low differentiation efficiency and unpredictable immunogenicity of allogeneic MSCs in vivo limit their success in therapeutic treatment. Herein, we evaluated the differentiation potential and immunogenicity of human placenta-derived MSCs manipulated with osteogenic priming and dedifferentiation process.
  
  
  
  MSCs from human placentas were subjected to osteogenic induction and then cultivated in osteogenic factor-free media; the obtained cell population was termed dedifferentiated mesenchymal stem cells (De-MSCs). De-MSCs were induced into osteo-, chondro- and adipo-differentiation in vitro. Cell proliferation was quantified by a Cell-Counting Kit-8 or tritiated thymidine ([(3)H]-TdR) incorporation. Meanwhile, the osteogenesis of De-MSCs in vivo was assayed by real-time PCR and histological staining. The expressions of stem cell markers and co-stimulatory molecules on De-MSCs and lymphocytes from primed BALB/c mouse with De-MSCs were determined by flow cytometry.
  
  
  
  De-MSCs exhibited some properties similar to MSCs including multiple differentiation potential and hypoimmunogenicity. Upon re-osteogenic induction, De-MSCs exhibited higher differentiation capability than MSCs both in vitro and in vivo. Of note, De-MSCs had upregulated immunogenicity in association with their osteogenesis, reflected by the alternated expressions of co-stimulatory molecules on the surface and decreased suppression on T cell activation. Functionally, De-MSC-derived osteoblasts could prime lymphocytes of peripheral blood and spleen in BALB/c mice in vivo.
  
  
  
  These data are of great significance for the potential application of De-MSCs as an alternative resource for regenerative medicine and tissue engineering. In order to avoid being rejected by the host during allogeneic De-MSC therapy, we suggest that immune intervention should be considered to boost the immune acceptance and integration because of the upregulated immunogenicity of De-MSCs with redifferentiation in clinical applications.
authors.affiliation: Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China.
authors.forename: Xuejie
authors.initials: X
authors.lastname: Fu
authors.affiliation: Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Yang
authors.affiliation: Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China.
authors.forename: Guichao
authors.initials: G
authors.lastname: Wang
authors.affiliation: Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine and i-Lab, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, People's Republic of China.
authors.forename: Guangcun
authors.initials: G
authors.lastname: Chen
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China. gyz_1982@yeah.net.|Key Laboratory of Stem Cell of Jiangsu Province, Institute of Medical Biotechnology, Soochow University, No.188 Shizi Street, Suzhou, 215006, People's Republic of China. gyz_1982@yeah.net.
authors.forename: Yanzheng
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China. shiqin@suda.edu.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D054337:Cell Dedifferentiation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D003470:Culture Media
keywords: Dedifferentiated mesenchymal stem cells; Immunogenicity; Mesenchymal stem cells; Osteogenesis