Open AccessAutocrine Action of Thrombospondin‐2 Determines the Chondrogenic Differentiation Potential and Suppresses Hypertrophic Maturation of Human Umbilical Cord Blood‐Derived Mesenchymal Stem Cells
Author(s) -
Jeong Sang Young,
Ha Jueun,
Lee Miyoung,
Jin Hye Jin,
Kim Dong Hyun,
Choi Soo Jin,
Oh Wonil,
Yang Yoon Sun,
Kim JaeSung,
Kim ByungGyu,
Chang Jeong Ho,
Cho DongHyung,
Jeon Hong Bae
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2120
Subject(s) - chondrogenesis , mesenchymal stem cell , biology , microbiology and biotechnology , stem cell , cellular differentiation , immunology , wharton's jelly , umbilical cord , genetics , gene
Abstract Previous studies have shown that mesenchymal stem cell (MSC)‐based therapies have varying efficacies for the treatment of various diseases, including cartilage defects. In this study, we demonstrated that the chondrogenic differentiation potential of human umbilical cord blood‐derived MSCs (hUCB‐MSCs) obtained from different individual donors varies, and we investigated the molecular basis for this variation. Microarray gene expression analysis identified thrombospondin‐2 ( TSP2 ) as a candidate gene underlying the interindividual variation in the chondrogenic differentiation potential of hUCB‐MSCs. To assess the association between TSP‐2 and the differentiation potential, we evaluated chondrogenic differentiation of hUCB‐MSCs treated with TSP2 siRNA. In addition, we studied the effect of supplementing exogenous recombinant TSP‐2 on TSP2 siRNA‐treated hUCB‐MSCs. We found that TSP‐2 autocrinally promoted chondrogenic differentiation of hUCB‐MSCs via the Notch signaling pathway, which was confirmed in MSCs from other sources such as bone marrow and adipose tissue. Interestingly, we observed that TSP‐2 attenuated hypertrophy, which inevitably occurs during chondrogenic differentiation of hUCB‐MSCs. Our findings indicated that the variable chondrogenic differentiation potential of MSCs obtained from different donors is influenced by the TSP‐2 level in the differentiating cells. Thus, the TSP‐2 level can be used as a marker to select MSCs with superior chondrogenic differentiation potential for use in cartilage regeneration therapy. S tem C ells 2015;33:3291–3303