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Human umbilical cord blood mesenchymal stem cells expansion via human fibroblast-derived matrix and their potentials toward regenerative application

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Abstract

Large expansion of human mesenchymal stem cells (MSCs) is of great interest for clinical applications. In this study, we examine the feasibility of human fibroblast-derived extracellular matrix (hFDM) as an alternative cell expansion setting. hFDM is obtained from decellularized extracellular matrix (ECM) derived from in vitro cultured human lung fibroblasts. Our study directly compares conventional platforms (tissue culture plastic (TCP), fibronectin (FN)-coated TCP) with hFDM using umbilical cord blood-derived MSCs (UCB-MSCs). Early cell morphology shows a rather rounded shape on TCP but highly elongated morphology on hFDM. Cell proliferation demonstrates that MSCs on hFDM were significantly better compared to the others in both 10 and 2% serum condition. Cell migration assay suggests that cell motility was improved and a cell migration marker CXCR4 was notably up-regulated on hFDM. MSCs differentiation into osteogenic lineage on hFDM was also very effective as examined via gene expression, von Kossa staining and alkaline phosphatase activity. In addition, as the MSCs were expanded on each substrate, transferred to 3D polymer mesh scaffolds and then cultivated for a while, the data found better cell proliferation and more CXCR4 expression with MSCs pre-conditioned on hFDM. Moreover, higher gene expression of stemness and engraftment-related markers was noticed with the hFDM group. Furthermore when UCB-MSCs expanded on TCP or hFDM were injected into emphysema (a lung disease) animal model, the results indicate that MSCs pre-conditioned on hFDM (with 2% serum) retain more advanced therapeutic efficacy on the improvement of emphysema than those on TCP. Current works demonstrate that compared to the conventional platforms, hFDM can be a promising source of cell expansion with a naturally derived biomimetic ECM microenvironment and may find some practical applications in regenerative medicine.

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Funding

This study was supported by the Korea Health Industry Development Institute (KHIDI) and funded by the Ministry of Health and Welfare (HI16C0133), Republic of Korea.

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Author notes

  1. Se Young Van and Yong Kwan Noh contributed equally to this work.

Authors and Affiliations

  1. Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea

    Se Young Van, Yong Kwan Noh & Kwideok Park

  2. Department of Biotechnology, Korea University, Seoul, 02841, Republic of Korea

    Yong Kwan Noh & Ik Hwan Kim

  3. Department of Biochemistry and Molecular Biology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, 05505, Republic of Korea

    Seong Who Kim

  4. Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea

    Yeon Mok Oh

  5. Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul, 02792, Republic of Korea

    Kwideok Park

Authors
  1. Se Young Van
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  2. Yong Kwan Noh
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Correspondence to Ik Hwan Kim or Kwideok Park.

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Van, S.Y., Noh, Y.K., Kim, S.W. et al. Human umbilical cord blood mesenchymal stem cells expansion via human fibroblast-derived matrix and their potentials toward regenerative application. Cell Tissue Res 376, 233–245 (2019). https://doi.org/10.1007/s00441-018-2971-2

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  • DOI: https://doi.org/10.1007/s00441-018-2971-2

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