分泌组、异种骨髓间充质干细胞、骨形态发生蛋白-2、羟基磷灰石颗粒及机械固定对大鼠临界尺寸骨缺损模型的影响
The Effect of Secretome, Xenogenic Bone Marrow-Derived Mesenchymal Stem Cells, Bone Morphogenetic Protein-2, Hydroxyapatite Granule and Mechanical Fixation in Critical-Size Defects of Rat Models.
作者信息
Dilogo Ismail Hadisoebroto, Fiolin Jessica, Canintika Annisa Feby, Pawitan Jeanne Adiwinata, Luviah Evah
机构信息
Department of Orthopedic and Traumatology, Faculty of Medicine, Universitas Indonesia-Dr Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia.
Stem Cell and Tissue Engineering Research Cluster, Indonesia Medical Education and Research Institute, Faculty of Medicine Universitas Indonesia.
出版信息
Arch Bone Jt Surg. 2022 Jan;10(1):17-22. doi: 10.22038/ABJS.2021.49539.2458.
BACKGROUND
Recent studies have shown that human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have several drawbacks in treating critical-sized bone defect (CSD). Secretome may offer considerable advantages over living cells in terms of potency, manufacturing and storing easiness, and potential as a ready-to-go osteoinductive agent. However, thus far, there are no studies regarding the efficacy of secretome in bone healing. The objective of this study is to investigate the effect of the secretome in rat models with CSD.
METHODS
This was an experimental study with post-test only control group design using 60 skeletally mature Sprague Dawley rat which was divided evenly into 5 treatment groups (MSC only, Secretome only, MSC + Secretome, MSC + Secretome + BMP-2, Control group using Normal Saline). We used Bone Marrow derived MSC in this research. The critical-sized bone defect was created by performing osteotomy and defect was treated according to the groups. Rats were sacrificed on 2nd and 4th week and we measured the radiological outcome using Radiographic Union Score for Tibia (RUST) and histomorphometric (callus, osseous, cartilage, fibrous, and void area) evaluation using Image J.
RESULTS
There was no difference in the weight of rats between groups before and after the intervention. RUST score in all intervention group is significantly higher than the control group, however, the MSC-only group was not statistically significant higher than the control group. There is no statistically significant difference in RUST Score between intervention groups.Histomorphometric evaluation showed that total callus formation is the widest in the MSC+Secretome+BMP-2 combination group while the osseous area is found highest on the secretome-only group.
CONCLUSION
Secretome, whether used solely or combined with BM-MSC and BMP-2, is a novel, potent bone-healing agent for CSD in rat models.
背景
最近的研究表明，人骨髓间充质干细胞（hBM-MSCs）在治疗临界尺寸骨缺损（CSD）方面存在若干缺点。分泌组在效力、制造和储存便利性以及作为即用型骨诱导剂的潜力方面可能比活细胞具有相当大的优势。然而，迄今为止，尚无关于分泌组在骨愈合中功效的研究。本研究的目的是探讨分泌组在CSD大鼠模型中的作用。
方法
这是一项仅设测试后对照组设计的实验研究，使用60只骨骼成熟的Sprague Dawley大鼠，将其平均分为5个治疗组（仅MSC组、仅分泌组、MSC+分泌组、MSC+分泌组+BMP-2组、使用生理盐水的对照组）。本研究使用骨髓来源的MSC。通过截骨术制造临界尺寸骨缺损，并根据分组对缺损进行治疗。在第2周和第4周处死大鼠，我们使用胫骨放射学愈合评分（RUST）测量放射学结果，并使用Image J进行组织形态计量学（骨痂、骨、软骨、纤维和空隙面积）评估。
结果
干预前后各组大鼠体重无差异。所有干预组的RUST评分均显著高于对照组，然而，仅MSC组在统计学上并不显著高于对照组。各干预组之间的RUST评分无统计学显著差异。组织形态计量学评估显示，在MSC+分泌组+BMP-2联合组中总骨痂形成最宽，而在仅分泌组中骨面积最高。
结论
分泌组，无论是单独使用还是与BM-MSC和BMP-2联合使用，都是一种用于大鼠模型CSD的新型、有效的骨愈合剂。
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