Prof Simon M Coola,b


aGlycotherapeutics Group, Institute of Medical Biology, Agency for Science, Technology and Research, Singapore 138648
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore 119288


The current and growing demand for adult stem cells for a range of therapies far outstrips the world’s ability to supply them. The safe, efficacious and scalable manufacturing of adult human mesenchymal stem cells (MSC) is central to the plans of all clinics, stem cell companies and related industries that seek to provide stem cell-based treatments for patients. This applies to not only cells for autologous use, but also cells used for wider allogenic application for many clinical conditions. However, MSCs remain quiescent when surgically isolated, and achieving sufficient cell numbers for therapeutic use is both time-intensive and extremely costly.  Providing patients with effective treatment options relies on maintaining the therapeutic potency of the cells after their surgical isolation and ex vivo expansion. Fibroblast growth factor-2 (FGF-2) supplementation increases MSC growth rates, yet its prolonged use can cause phenotypic drift in the population of cells.  MSCs however, also produce FGF-2 that interacts with cell surface heparan sulfate (HS) sugars to form complexes with FGF receptors that propagate mitogenic signals. We have purified distinct HS preparations that bind endogenously-produced FGF-2 and potentiate FGF signalling. Our data show that supplementation of MSC cultures with these FGF-2-binding HS preparations increases endogenous FGF-2 production and bioavailability and enhances MSC expansion without adversely affecting multipotency.  Moreover, MSCs exposed to this HS adjuvant have increased reparative capacity when used to treat osteochondral lesions in rodent and pig models. Our data shows that HS agents can enhance ligand/receptor interactions and exert powerful effects on the cellular microenvironment that controls cell fate decisions.  These results highlight the considerable potential that HS materials have on the bioprocessing of MSCs intended for clinical use.


AEB 301