Open AccessRescuing mesenchymal stem cell regenerative properties on hydrogel substrates post serial expansion
Author(s) -
Rao Varsha V.,
Vu Michael K.,
Ma Hao,
Killaars Anouk R.,
Anseth Kristi S.
Publication year - 2019
Publication title -
bioengineering and translational medicine
Language(s) - English
Resource type - Journals
ISSN - 2380-6761
DOI - 10.1002/btm2.10104
Subject(s) - mesenchymal stem cell , self healing hydrogels , microbiology and biotechnology , stromal cell , stem cell , chemistry , ex vivo , regenerative medicine , tissue engineering , cell growth , ethylene glycol , in vivo , biomedical engineering , in vitro , biophysics , biology , biochemistry , cancer research , medicine , organic chemistry
Abstract The use of human mesenchymal stem/stromal cells (hMSCs) in most clinical trials requires millions of cells/kg, necessitating ex vivo expansion typically on stiff substrates (tissue culture polystyrene [TCPS]), which induces osteogenesis and replicative senescence. Here, we quantified how serial expansion on TCPS influences proliferation, expression of hMSC‐specific surface markers, mechanosensing, and secretome. Results show decreased proliferation and surface marker expression after five passages (P5) and decreased mechanosensing ability and cytokine production at later passages (P11‐P12). Next, we investigated the capacity of poly(ethylene glycol) hydrogel matrices (E ~ 1 kPa) to rescue hMSC regenerative properties. Hydrogels reversed the reduction in cell surface marker expression observed at P5 on TCPS and increased secretion of cytokines for P11 hMSCs. Collectively, these results show that TCPS expansion significantly changes functional properties of hMSCs. However, some changes can be rescued by using hydrogels, suggesting that tailoring material properties could improve in vitro expansion methods.