Abstract

Synovial mesenchymal stem cell (SMSC) is the promising cell source of cartilage regeneration but has several issues to overcome such as limited cell proliferation and heterogeneity of cartilage regeneration ability. Previous reports demonstrated that basic fibroblast growth factor (bFGF) can promote proliferation and cartilage differentiation potential of MSCs in vitro, although no reports show its beneficial effect in vivo. The purpose of this study is to investigate the promoting effect of bFGF on cartilage regeneration using human SMSC in vivo. SMSCs were cultured with or without bFGF in a growth medium, and 2 × 105 cells were aggregated to form a synovial pellet. Synovial pellets were implanted into osteochondral defects induced in the femoral trochlea of severe combined immunodeficient mice, and histological evaluation was performed after eight weeks. The presence of implanted SMSCs was confirmed by the observation of human vimentin immunostaining-positive cells. Interestingly, broad lacunae structures and cartilage substrate stained by Safranin-O were observed only in the bFGF (+) group. The bFGF (+) group had significantly higher O’Driscoll scores in the cartilage repair than the bFGF (−) group. The addition of bFGF to SMSC growth culture may be a useful treatment option to promote cartilage regeneration in vivo.

Highlights

  • Articular cartilage has a poor self-healing ability and the conventional surgical treatments and cell therapies for cartilage injuries, such as bone marrow stimulation, autologous osteochondral transplantation, and autologous chondrocyte implantation (ACI), have not yielded full recovery of normal cartilage [1]

  • Fibroblast growth factors (FGFs) control the migration, proliferation, differentiation, and survival of various cells and affect the expression of other factors involved in the regenerative response [22]

  • FGFR1–4 has been identified in both humans and mice [21]

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Summary

Introduction

Articular cartilage has a poor self-healing ability and the conventional surgical treatments and cell therapies for cartilage injuries, such as bone marrow stimulation, autologous osteochondral transplantation, and autologous chondrocyte implantation (ACI), have not yielded full recovery of normal cartilage [1]. Various pretreatment methods to enhance the cartilage differentiation potential of MSCs have been reported [10,11,12]; we showed that a low oxygen tension prevented cellular senescence and promoted the proliferative and chondrogenic differentiation capacity of human SMSCs in vitro [13]. None of these reports succeed to demonstrate the positive effects in vivo. The basic fibroblast growth factor (bFGF) has been widely reported to enhance the potential of proliferation and cartilaginous differentiation of MSCs in vitro [14,15,16]

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