4.7 Article

Development and Angiogenic Potential of Cell-Derived Microtissues Using Microcarrier-Template

Journal

BIOMEDICINES
Volume 9, Issue 3, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines9030232

Keywords

poly-lactic acid microcarriers; Cultispher (R) S; rat bone marrow mesenchymal stem cells; microtissue; cell-derived matrix; angiogenesis

Funding

  1. Severo Ochoa Program for Centers of Excellence in RD 2016-2019
  2. European Commission-ERANET [nAngioderm JTC2018-103]
  3. Spanish network of cell therapy (TERCEL)
  4. European Regional Development Fund (FEDER)
  5. Spanish Ministry of Science [MAT2015-68906-R, RTI2018096320-B-C21]
  6. Spanish Ministry of Economy, Industry and Competitiveness [BES-2016077182]
  7. BEST Postdoctoral Programme - European Commission under the Horizon 2020 Marie Sklodowska-Curie Actions COFUND scheme [712754]
  8. Spanish Ministry of Science and Competitiveness [SEV-2014-0425]
  9. Marie Sklodowska-Curie (2019) grant [712754]
  10. Severo Ochoa (2014) grant [SEV-2014-0425]
  11. Severo Ochoa (2018) grant [CEX2018-000789-S]

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The study focuses on using cell-derived matrix microtissues to mimic tissue conditions and promote vascularization. By seeding rat bone marrow mesenchymal stem cells on poly-lactic acid and microcarriers, cells are able to generate extracellular matrix and provide a complex environment with angiogenic potential.
Tissue engineering and regenerative medicine approaches use biomaterials in combination with cells to regenerate lost functions of tissues and organs to prevent organ transplantation. However, most of the current strategies fail in mimicking the tissue's extracellular matrix properties. In order to mimic native tissue conditions, we developed cell-derived matrix (CDM) microtissues (MT). Our methodology uses poly-lactic acid (PLA) and Cultispher(R) S microcarriers' (MCs') as scaffold templates, which are seeded with rat bone marrow mesenchymal stem cells (rBM-MSCs). The scaffold template allows cells to generate an extracellular matrix, which is then extracted for downstream use. The newly formed CDM provides cells with a complex physical (MT architecture) and biochemical (deposited ECM proteins) environment, also showing spontaneous angiogenic potential. Our results suggest that MTs generated from the combination of these two MCs (mixed MTs) are excellent candidates for tissue vascularization. Overall, this study provides a methodology for in-house fabrication of microtissues with angiogenic potential for downstream use in various tissue regenerative strategies.

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