Effect of heparin on the biological properties and molecular signature of human mesenchymal stem cells

Effect of heparin on the biological properties and molecular signature of human mesenchymal stem cells

Gene

10.1016/j.gene.2015.10.039

https://doi.org/10.1016/j.gene.2015.10.039

Ling Ling, Emily T. Camilleri, Torben Helledie, Rebekah M. Samsonraj, Drew M. Titmarsh, Ren Jie Chua, Oliver Dreesen, Christian Dombrowski, David A. Rider, Mario Galindo, Ian Lee, Wanjin Hong, James H. Hui, Victor Nurcombe, Andre J. van Wijnen, Simon M. Cool

17 October 2015

Ling Ling, Emily T. Camilleri, Torben Helledie, Rebekah M. Samsonraj, Drew M. Titmarsh, Ren Jie Chua, Oliver Dreesen, Christian Dombrowski, David A. Rider, Mario Galindo, Ian Lee, Wanjin Hong, James H. Hui, Victor Nurcombe, Andre J. van Wijnen, Simon M. Cool, Effect of heparin on the biological properties and molecular signature of human mesenchymal stem cells, Gene, Volume 576, Issue 1, Part 2, 2016, Pages 292-303, ISSN 0378-1119, https://doi.org/10.1016/j.gene.2015.10.039.

Chronic use of heparin as an anti-coagulant for the treatment of thrombosis or embolism invokes many adverse systemic events including thrombocytopenia, vascular reactions and osteoporosis. Here, we addressed whether adverse effects might also be directed to mesenchymal stem cells that reside in the bone marrow compartment. Harvested human bone marrow-derived mesenchymal stem cells (hMSCs) were exposed to varying doses of heparin and their responses profiled. At low doses (< 200 ng/ml), serial passaging with heparin exerted a variable effect on hMSC proliferation and multipotentiality across multiple donors, while at higher doses (≥ 100 μg/ml), heparin supplementation inhibited cell growth and increased both senescence and cell size. Gene expression profiling using cDNA arrays and RNA-seq analysis revealed pleiotropic effects of low-dose heparin on signaling pathways essential to hMSC growth and differentiation (including the TGFβ/BMP superfamily, FGFs, and Wnts). Cells serially passaged in low-dose heparin possess a donor-dependent gene signature that reflects their altered phenotype. Our data indicate that heparin supplementation during the culturing of hMSCs can alter their biological properties, even at low doses. This warrants caution in the application of heparin as a culture supplement for the ex vivo expansion of hMSCs. It also highlights the need for careful evaluation of the bone marrow compartment in patients receiving chronic heparin treatment.

PublisherCopyrights

This work was also supported by National Medical Research Council of Singapore (NMRC) and in part by National Institutes of Health Grants AR49069 (AvW).

The author manuscript is available for free at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330685/

https://oar.a-star.edu.sg/communities-collections/articles/16064

0378-1119
1879-0038

Institute of Molecular and Cell Biology