Wang Linfeng, Guan Changbiao, Zhang Tao, Zhou Yongchun, Liu Yuqian, Hu Jianzhong, Xu Daqi, Lu Hongbin
Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China.
Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China.
J Orthop Translat. 2024 Jun 20;47:87-96. doi: 10.1016/j.jot.2024.05.005. eCollection 2024 Jul.
Bone marrow mesenchymal stem cells (BMSCs) have immense potential in applications for the enhancement of tendon-bone (T-B) healing. Recently, it has been well-reported that skeletal stem cells (SSCs) could induce bone and cartilage regeneration. Therefore, SSCs represent a promising choice for cell-based therapies to improve T-B healing. In this study, we aimed to compare the therapeutic potential of SSCs and BMSCs for tendon-bone healing.
SSCs and BMSCs were isolated by flow cytometry, and their proliferation ability was measured by CCK-8 assay. The osteogenic, chondrogenic, and adipogenic gene expression in cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair, and the mice were then randomly allocated to 4 groups: control group (tendon-bone interface without any treatment), hydrogel group (administration of blank hydrogel into the tendon-bone interface), hydrogel + BMSCs group (administration of hydrogel with BMSCs into the tendon-bone interface), and hydrogel + SSCs group (administration of hydrogel with SSCs into the tendon-bone interface). Histological staining, Micro-computed tomography (Micro-CT) scanning, biomechanical testing, and qRT-PCR were performed to assay T-B healing at 4 and 8 weeks after surgery.
SSCs showed more cell proportion, exhibited stronger multiplication capacity, and expressed higher osteogenic and chondrogenic markers and lower adipogenic markers than BMSCs. In vivo assay, the SSCs group showed a better-maturated interface which was characterized by richer chondrocytes and more proteoglycan deposition, as well as more newly formed bone at the healing site and increased mechanical properties when compared to other there groups. qRT-PCR analysis revealed that the healing interface in the SSCs group expressed more transcription factors essential for osteogenesis and chondrogenesis than the interfaces in the other groups.
Overall, the results demonstrated the superior therapeutic potential of SSCs over BMSCs in tendon-bone healing.
This current study provides valuable insights that SSCs may be a more effective cell therapy for enhancing T-B healing compared to BMSCs.
骨髓间充质干细胞（BMSCs）在促进肌腱-骨（T-B）愈合的应用中具有巨大潜力。最近，有充分报道称骨骼干细胞（SSCs）可诱导骨和软骨再生。因此，SSCs是基于细胞疗法改善T-B愈合的一个有前景的选择。在本研究中，我们旨在比较SSCs和BMSCs对肌腱-骨愈合的治疗潜力。
通过流式细胞术分离SSCs和BMSCs，并通过CCK-8法检测其增殖能力。通过定量实时聚合酶链反应（qRT-PCR）检测细胞中的成骨、成软骨和脂肪生成基因表达。C57BL/6小鼠接受单侧冈上肌腱离断和修复，然后将小鼠随机分为4组：对照组（肌腱-骨界面未进行任何处理）、水凝胶组（向肌腱-骨界面注入空白水凝胶）、水凝胶+BMSCs组（向肌腱-骨界面注入含BMSCs的水凝胶）和水凝胶+SSCs组（向肌腱-骨界面注入含SSCs的水凝胶）。在术后4周和8周进行组织学染色、显微计算机断层扫描（Micro-CT）、生物力学测试和qRT-PCR，以评估T-B愈合情况。
与BMSCs相比，SSCs显示出更高的细胞比例、更强的增殖能力，并且表达更高的成骨和成软骨标志物以及更低的脂肪生成标志物。在体内实验中，与其他三组相比，SSCs组显示出更好的成熟界面，其特征为软骨细胞更丰富、蛋白聚糖沉积更多，愈合部位新形成的骨更多，机械性能增强。qRT-PCR分析显示，SSCs组的愈合界面表达的成骨和软骨生成必需转录因子比其他组的界面更多。
总体而言，结果表明在肌腱-骨愈合方面，SSCs的治疗潜力优于BMSCs。
本研究提供了有价值的见解，即与BMSCs相比，SSCs可能是一种更有效的促进T-B愈合的细胞疗法。
