Bone marrow-derived human mesenchymal stem/stromal cells (hMSCs) are multipotent cells capable of differentiating into cell types found in tissues of the mesoderm (bone, cartilage, fat), ectoderm (epithelium, neural), and endoderm (muscle, gut, lung)1. hMSCs are one of the most widely used cell types in clinical trials with over 800 trials registered worldwide. Millions of cells/kg are needed for efficacy in treatments, necessitating ex vivo expansion2. To obtain high cell numbers, hMSCs are expanded on stiff substrates (tissue culture plastic) where they begin to lose their regenerative properties. When cultured on soft PEG hydrogels (E~1kPa), some properties lost with expansion can be rescued suggesting that tailoring material properties may be useful for improving in vitro methods for serially expanding hMSCs3.
While regenerative medicine applications exploit the multipotency and differentiation of hMSCs, hMSCs are also known to secrete many trophic factors that impact therapeutic outcomes. hMSCs secrete various cytokines and chemokines involved in immunomodulation, angiogenesis, and wound healing. While the biomaterial field has greatly explored the mechanical cues governing differentiation, very little is known about how changes in 3D microenvironment can affect the factors that hMSCs secrete. My current project is focused on developing biomaterial systems to study and control the hMSC secretome for therapeutic and regenerative medicine applications.
- Dominici, M. et al. Cytotherapy 8, 315–317 (2006).
- Billing, A. M. et al. Sci. Rep. 6, 1–15 (2016).
- Rao, V. V. et al. Bioeng. Transl. Med. 1–10 (2018).