Background

A critical size bone defect is a clinical scenario in which bone is lost or excised due to trauma, infection, tumor, or other causes, and cannot completely heal spontaneously. The most common treatment for this condition is autologous bone grafting to the defect site. However, autologous bone graft is often insufficient in quantity or quality for transplantation to these large defects. Recently, tissue engineering methods using mesenchymal stem cells (MSCs) have been proposed as an alternative treatment. However, the underlying biological principles and optimal techniques for tissue regeneration of bone using stem cell therapy have not been completely elucidated.

Methods

In this study, we compare the early cellular dynamics of healing between bone graft transplantation and MSC therapy in a murine chronic femoral critical-size bone defect. We employ high-dimensional mass cytometry to provide a comprehensive view of the differences in cell composition, stem cell functionality, and immunomodulatory activity between these two treatment methods one week after transplantation.

Results

We reveal distinct cell compositions among tissues from bone defect sites compared with original bone graft, show active recruitment of MSCs to the bone defect sites, and demonstrate the phenotypic diversity of macrophages and T cells in each group that may affect the clinical outcome.

Conclusion

Our results provide critical data and future directions on the use of MSCs for treating critical size defects to regenerate bone.

Translational Potential of this article: This study showed systematic comparisons of the cellular and immunomodulatory profiles among different interventions to improve the healing of the critical-size bone defect. The results provided potential strategies for designing robust therapeutic interventions for the unmet clinical need of treating critical-size bone defects.

中文翻译：

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小鼠临界尺寸缺损骨缺损愈合过程中骨移植移植和间充质干细胞治疗的差异动力学

背景

临界尺寸骨缺损是一种临床情况，其中由于外伤、感染、肿瘤或其他原因导致骨丢失或切除，并且不能完全自发愈合。这种情况最常见的治疗方法是在缺损部位进行自体骨移植。然而，自体骨移植在数量或质量上往往不足以移植到这些大缺陷。最近，已提出使用间充质干细胞 (MSCs) 的组织工程方法作为替代治疗方法。然而，使用干细胞疗法进行骨组织再生的基本生物学原理和最佳技术尚未完全阐明。

方法

在这项研究中，我们比较了小鼠慢性股骨临界尺寸骨缺损中骨移植移植和 MSC 治疗之间愈合的早期细胞动力学。我们采用高维质谱流式细胞仪，全面了解移植一周后这两种治疗方法在细胞组成、干细胞功能和免疫调节活性方面的差异。

结果

我们揭示了与原始骨移植物相比，骨缺损部位组织中不同的细胞组成，显示 MSCs 积极募集到骨缺损部位，并证明每组中巨噬细胞和 T 细胞的表型多样性可能会影响临床结果。

结论

我们的研究结果为使用 MSC 治疗临界尺寸缺陷以再生骨提供了关键数据和未来方向。

本文的转化潜力：本研究显示了不同干预措施之间细胞和免疫调节谱的系统比较，以改善临界尺寸骨缺损的愈合。该结果为设计稳健的治疗干预措施提供了潜在的策略，以满足治疗临界尺寸骨缺损的未满足临床需求。