Enhancing the Efficacy of Stem Cell Therapy with Glycosaminoglycans

Abstract

Summary: Human mesenchymal stem cell (hMSC) therapy offers significant potential for osteochondral regeneration. Such applications require their ex vivo expansion in media frequently supplemented with fibroblast growth factor 2 (FGF2). Particular heparan sulfate (HS) fractions stabilize FGF2-FGF receptor complexes. We show that an FGF2-binding HS variant (HS8) accelerates the expansion of freshly isolated bone marrow hMSCs without compromising their naivety. Importantly, the repair of osteochondral defects in both rats and pigs is improved after treatment with HS8-supplemented hMSCs (MSCHS8), when assessed histologically, biomechanically, or by MRI. Thus, supplementing hMSC culture media with an HS variant that targets endogenously produced FGF2 allows the elimination of exogenous growth factors that may adversely affect their therapeutic potency. : This study highlights a novel strategy to improve cartilage repair using hMSCs cultured with heparan sulfates that target and stabilize fibroblast growth factor 2. The work is focused on developing bio-additives that prevent the loss of hMSCs stemness during their ex vivo expansion that is important for maintaining their therapeutic utility. Keywords: heparan sulfate, stemness, potency, ex vivo expansion, FGF2, efficacy, osteochondral regeneration, cartilage repair