Abstract

Allogeneic bone-marrow mesenchymal stem cells (BMSCs) can promote bone regeneration and substitute for autologous BMSCs if autologous sources are unavailable, but the efficacy of bone regeneration by allogeneic BMSCs is still inconsistent. A Lewis rat cranium defect model was used to investigate the efficacy of bone regeneration between autologous and allogeneic BMSCs in gelatin-nanohydroxyapatite cryogel scaffolds. BMSCs from Wistar rats served as the allogeneic cell lineage. The full-thickness cranium defects were treated by either blank control, cryogel only, allogeneic BMSC-seeded cryogel, or autologous BMSC-seeded cryogel (n = 5). Bone regeneration was monitored by micro-computed tomography and examined histologically at week 12. In addition, we assessed the immune responses in vitro by mixed lymphocyte reaction (MLR) assay and CD4+ immunochemistry staining ex vivo. The MLR showed that allogeneic BSMCs elicited a weak immune response on day 14 that progressively attenuated by day 28. In vivo, the bone regeneration in allogeneic BMSCs was inferior at week 4, but progressively matched the autologous BMSCs by week 12. Our results suggest that allogeneic BMSCs can serve as an alternative source for bone regeneration.

Highlights

  • Restoring a bone defect remains a challenging clinical problem

  • This study aims to investigate the potential application of allogeneic bone-marrow mesenchymal stem cells (BMSCs) in bone regeneration via a rat cranium defect model and compare the outcomes of bone regeneration between allogeneic and autologous BMSCs seeded in gelatin-nHAP cryogels

  • T(DN,AEP) + TNBMASPC+ BpMopSuClaptoiopnuslaotritoend sfroormtedBMfroSmC cBoMloSnCiecsofloorntiheesirfoirncthreeairseidncorsetaesoegdenoisctedoigffeenreicntdiaiftfieornenptoitaetniotnial. potential. (F) Osteogenic differentiation demonstrated by positive Alkaline Phosphatase (ALP) staining and calcium (Ca) de(Fp)oOsistitoenogsetaniincidnigffaetrednatyia2t8io. nScdaelemboanrs=tr4a0te0dμbmy.positive ALP staining and calcium (Ca) deposition staining at day 28

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Summary

Introduction

Surgeons can reconstruct defects with autologous bone tissue transfer, but the need for a donor site increases overall morbidity and patient discomfort. Mesenchymal stem cells (MSCs) of various origins, such as adipose, bone marrow, dental pulp, and umbilical cord blood, have shown osteogenic potential [3,4]. Bone-marrow mesenchymal stem cells (BMSCs) demonstrate a superior osteogenic effect compared to other sources [5]. The application of BMSCs has already been demonstrated in clinical settings [6,7]. They can be impractical because the quality and quantity of MSCs degenerate with the donor’s age and underlying medical conditions, such as diabetic mellitus or immunocompromised status [8,9]. Allogeneic MSCs may serve as an alternative cell source, with the potential to be expanded and preserved in advance, improving accessibility [10]

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