Comparison of bone regenerative capacity of donor-matched human adipose\u2013derived and bone marrow mesenchymal stem cells

Samih Mohamed-Ahmed,Kamal Mustafa,Heidi Espedal,Inge Fristad,Ahmad Rashad,Shaza B Idris,Hallvard Vindenes,Mohammed A Yassin,Anna Finne-Wistrand

doi:10.1007/s00441-020-03315-5

Abstract

Adipose-derived stem cells (ASC) have been used as an alternative to bone marrow mesenchymal stem cells (BMSC) for bone tissue engineering. However, the efficacy of ASC in bone regeneration in comparison with BMSC remains debatable, since inconsistent results have been reported. Comparing ASC with BMSC obtained from different individuals might contribute to this inconsistency in results. Therefore, this study aimed to compare the bone regenerative capacity of donor-matched human ASC and BMSC seeded onto poly(l-lactide-co-ε-caprolactone) scaffolds using calvarial bone defects in nude rats. First, donor-matched ASC and BMSC were seeded onto the co-polymer scaffolds to evaluate their in vitro osteogenic differentiation. Seeded scaffolds and scaffolds without cells (control) were then implanted in calvarial defects in nude rats. The expression of osteogenesis-related genes was examined after 4 weeks. Cellular activity was investigated after 4 and 12 weeks. Bone formation was evaluated radiographically and histologically after 4, 12, and 24 weeks. In vitro, ASC and BMSC demonstrated mineralization. However, BMSC showed higher alkaline phosphatase activity than ASC. In vivo, human osteogenesis–related genes Runx2 and collagen type I were expressed in defects with scaffold/cells. Defects with scaffold/BMSC had higher cellular activity than defects with scaffold/ASC. Moreover, bone formation in defects with scaffold/BMSC was greater than in defects with scaffold/ASC, especially at the early time-point. These results suggest that although ASC have the potential to regenerate bone, the rate of bone regeneration with ASC may be slower than with BMSC. Accordingly, BMSC are more suitable for bone regenerative applications.

Highlights

Repair of skeletal defects resulting from trauma, degenerative diseases, and tumor resection remains a medical challenge
Previous studies have compared the in vivo capacity of Adipose-derived stem cells (ASC) and bone marrow mesenchymal stem cells (BMSC) in bone regeneration to evaluate the effect of these mesenchymal stem cells (MSC) for bone tissue engineering (BTE) (Bothe et al 2018; Degano et al 2008; Freitas et al 2019; Jo et al 2013; Kang et al 2012; Kargozar et al 2018; Kim et al 2014; Lin et al 2009; Niemeyer et al 2010; Stockmann et al 2012; Walmsley et al 2016; Wen et al 2013; Xu et al 2017)
ASC and BMSC demonstrated the expression of Stro-1, but the expression was higher in BMSC (Fig. 1 c and d)

Summary

Introduction

Repair of skeletal defects resulting from trauma, degenerative diseases, and tumor resection remains a medical challenge. Previous studies have compared the in vivo capacity of ASC and BMSC in bone regeneration to evaluate the effect of these MSC for BTE (Bothe et al 2018; Degano et al 2008; Freitas et al 2019; Jo et al 2013; Kang et al 2012; Kargozar et al 2018; Kim et al 2014; Lin et al 2009; Niemeyer et al 2010; Stockmann et al 2012; Walmsley et al 2016; Wen et al 2013; Xu et al 2017). Comparing the in vivo bone regenerative capacity of donor-matched human BMSC and ASC should provide more reliable results

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Conclusion