Enhanced ex vivo expansion of adult mesenchymal stem cells by fetal mesenchymal stem cell ECM
Ng, Chee Ping
Mohamed Sharif, Abdul Rahim
Heath, Daniel E.
Chow, John W.
Zhang, Claire B. Y.
Chan-Park, Mary B.
Hammond, Paula T.
Chan, Jerry Kok Yen
Griffith, Linda G.
Date of Issue2014
School of Chemical and Biomedical Engineering
Singapore-MIT Alliance Programme
Large-scale expansion of highly functional adult human mesenchymal stem cells (aMSCs) remains technologically challenging as aMSCs lose self renewal capacity and multipotency during traditional long-term culture and their quality/quantity declines with donor age and disease. Identification of culture conditions enabling prolonged expansion and rejuvenation would have dramatic impact in regenerative medicine. aMSC-derived decellularized extracellular matrix (ECM) has been shown to provide such microenvironment which promotes MSC self renewal and “stemness”. Since previous studies have demonstrated superior proliferation and osteogenic potential of human fetal MSCs (fMSCs), we hypothesize that their ECM may promote expansion of clinically relevant aMSCs. We demonstrated that aMSCs were more proliferative (∼1.6×) on fMSC-derived ECM than aMSC-derived ECMs and traditional tissue culture wares (TCPS). These aMSCs were smaller and more uniform in size (median ± interquartile range: 15.5 ± 4.1 μm versus 17.2 ± 5.0 μm and 15.5 ± 4.1 μm for aMSC ECM and TCPS respectively), exhibited the necessary biomarker signatures, and stained positive for osteogenic, adipogenic and chondrogenic expressions; indications that they maintained multipotency during culture. Furthermore, fMSC ECM improved the proliferation (∼2.2×), size (19.6 ± 11.9 μm vs 30.2 ± 14.5 μm) and differentiation potential in late-passaged aMSCs compared to TCPS. In conclusion, we have established fMSC ECM as a promising cell culture platform for ex vivo expansion of aMSCs.
DRNTU::Engineering::Chemical engineering::Biochemical engineering
© 2014 The Author(s).This is the author created version of a work that has been peer reviewed and accepted for publication by Biomaterials, Elsevier Ltd. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [DOI:http://dx.doi.org/10.1016/j.biomaterials.2014.01.081].