Mesenchymal stem cell-derived extracellular matrices assembled in the presence of high molecular weight hyaluronic acid exhibit anti-inflammatory properties
Refereed conference paper presented and published in conference proceedings


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AbstractCell-based therapies are facing many challenges as the hostile inflammatory and ischemic environment in the affected tissue impairs integration, survival and hence therapy efficacy upon direct implantation. Nevertheless, the cellular secretome was shown to augment tissue healing and even regeneration. So far, the major focus for the related mechanism of action lied on the soluble paracrine factors. We hypothesized that the insoluble fraction of the cellular secretome, namely the extracellular matrix (ECM), would also hold a pro-regenerative potential. Hence, we decided to engineer tailor-made ECM in vitro.

Mesenchymal stem cells (MSCs) were allowed to assemble their ECM in the presence of exogenously added high molecular weight hyaluronic acid (HMWHA) to harness the anti-inflammatory and pro-regenerative potential of both components.

Indeed, supplementation of HMWHA to human bone marrow MSC (bmMSC) cultures resulted in increased expression levels of anti-inflammatory cytokine interleukin 10.

Addition of exogenous HMWHA over a time course of 2 to 6 days, enhanced the deposition of a bmMSC-derived ECM in a dose dependent manner. The ECM was enriched in provisional matrix components HA and fibrillar fibronectin.

Next, the engineered matrices were decellularized and investigated for their effect on macrophage polarization. THP-1 cells (human monocytic cell line) were differentiated into macrophages (MØ), seeded on decellularized ECMs and pulsed with pro-inflammatory factors to induce polarization into a pro-inflammatory phenotype (M1). As quantified by ELISA for TNFα, engineered matrices impaired macrophage polarization towards M1.

The HMWHA-mediated enhanced deposition of an anti-inflammatory ECM enables us to construct a bio-instructive material to promote healing and regeneration in diseased tissues facing chronic inflammation.
All Author(s) ListMarisa ASSUNÇÃO, Anna BLOCKI
Name of ConferenceTERMIS European Chapter Meeting 2019
Start Date of Conference27/05/2019
End Date of Conference31/05/2019
Place of ConferenceRhodes
Country/Region of ConferenceGreece
Year2019
Month5
LanguagesEnglish-United States

Last updated on 2019-17-06 at 15:06