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

  • Se Young Van
  • Yong Kwan Noh
  • Seong Who Kim
  • Yeon Mok Oh
  • Ik Hwan Kim
  • Kwideok Park
Regular Article

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.

Keywords

Extracellular matrix (ECM) Human fibroblast-derived matrix (hFDM) Umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) MSCs expansion Emphysema 

Notes

Funding information

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.

Compliance with ethical standards

Competing interest

The authors declare that they have no competing financial interests.

Supplementary material

441_2018_2971_MOESM1_ESM.docx (4.5 mb)
ESM 1 (DOCX 4645 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Center for BiomaterialsKorea Institute of Science and Technology (KIST)SeoulRepublic of Korea
  2. 2.Department of BiotechnologyKorea UniversitySeoulRepublic of Korea
  3. 3.Department of Biochemistry and Molecular Biology, College of Medicine, Asan Medical CenterUniversity of UlsanSeoulRepublic of Korea
  4. 4.Department of Pulmonary and Critical Care Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
  5. 5.Division of Bio-Medical Science and Technology, KIST SchoolKorea University of Science and Technology (UST)SeoulRepublic of Korea

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