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Functional characteristics of mesenchymal stem cells derived from the adipose tissue of a patient with achondroplasia

  • Jeong-Ran Park
  • Hanbyeol Lee
  • Chung-Hyo Kim
  • Seok-Ho Hong
  • Kwon-Soo Ha
  • Se-Ran YangEmail author
Article

Abstract

Mesenchymal stem cells (MSCs) can be isolated from various tissues including bone marrow, adipose tissue, skin dermis, and umbilical Wharton’s jelly as well as injured tissues. MSCs possess the capacity for self-renewal and the potential for differentiation into adipogenic, osteogenic, and chondrogenic lineages. However, the characteristics of MSCs in injured tissues, such as achondroplasia (ACH), are not well known. In this study, we isolated MSCs from human subcutaneous adipose (ACH-SAMSCs) tissue and circumjacent human adipose tissue of the cartilage (ACH-CAMSCs) from a patient with ACH. We then analyzed the characterization of ACH-SAMSCs and ACH-CAMSCs, compared with normal human dermis-derived MSCs (hDMSCs). In flow cytometry analysis, the isolated ACH-MSCs expressed low levels of CD73, CD90, and CD105, compared with hDMSCs. Moreover, both ACH- SAMSCs and ACH-CAMSCs had constitutionally overactive fibroblast growth factor receptor 3 (FGFR3) and exhibited significantly reduced osteogenic differentiation, compared to enhanced adipogenic differentiation. The activity of extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK) was increased in ACH-MSCs. In addition, the efficacy of osteogenic differentiation was slightly restored in osteogenic differentiation medium with MAPKs inhibitors. These results suggest that they play essential roles in MSC differentiation toward adipogenesis in ACH pathology. In conclusion, the identification of the characteristics of ACH-MSCs and the favoring of adipogenic differentiation via the FGFR3/MAPK axis might help to elucidate the pathogenic mechanisms relevant to other skeletal diseases and could provide targets for therapeutic interventions.

Keywords

Achondroplasia Mesenchymal stem cell Adipogenesis FGFR3 

Notes

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2013R1A1A2057787, NRF-2014R1A2A2A01003737), 2015 research grant from Kangwon National University (520150343) and 2009 Kangwon National University Hospital Grant.

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Copyright information

© The Society for In Vitro Biology 2016

Authors and Affiliations

  • Jeong-Ran Park
    • 1
    • 5
  • Hanbyeol Lee
    • 1
  • Chung-Hyo Kim
    • 2
  • Seok-Ho Hong
    • 3
  • Kwon-Soo Ha
    • 4
  • Se-Ran Yang
    • 1
    • 5
    • 6
    Email author
  1. 1.Department of Thoracic and Cardiovascular SurgeryKangwon National UniversityChuncheonRepublic of Korea
  2. 2.Department of NeurosurgeryKangwon National University HospitalChuncheonRepublic of Korea
  3. 3.Department of Internal MedicineKangwon National UniversityChuncheonRepublic of Korea
  4. 4.Department of Molecular and Cellular BiochemistryKangwon National University School of MedicineChuncheonSouth Korea
  5. 5.Institute of Medical ScienceKangwon National UniversityChuncheonRepublic of Korea
  6. 6.Stem Cell InstituteKangwon National UniversityChuncheonRepublic of Korea

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