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关节内注射地塞米松对骨髓间充质干细胞移植治疗兔全层软骨缺损的影响

Intraarticular Administration of Dexamethasone after Mesenchymal Stem Cells Implantation Does Not Improve Significantly the Treatment of Preestablished Full-Thickness Chondral Defect in a Rabbit Model.

机构信息

Instituto de Ciencias, Facultad de Medicina Clinica Alemana, Universidad del Desarrollo, Santiago, Chile.

Instituto de Ciencias, Facultad de Medicina Clinica Alemana, Universidad del Desarrollo, Santiago, Chile ; Clinica Alemana, Santiago, Chile.

出版信息

Cartilage. 2013 Apr;4(2):144-52. doi: 10.1177/1947603512472696.

DOI:10.1177/1947603512472696
PMID:26069657
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4297101/
Abstract

OBJECTIVE

The aim of this study was to evaluate the contribution to hyaline cartilage regeneration of dexamethasone intraarticular administration after autologous mesenchymal stem cells (MSCs) implantation into a preestablished knee full-thickness chondral defect.

DESIGN

Full-thickness chondral defects of 4.5 × 4.5 mm(2) were surgically made in both medial femoral condyles of adult male New Zealand rabbits. Two weeks later, autologous ex vivo expanded bone marrow-derived MSCs were embedded in hyaluronic acid and implanted into the chondral defects. Immediately and every week after the intervention, dexamethasone 0.25 mg/kg was intraarticularly administered (MSC/dexa-treated group). Six weeks after MSC transplantation, the animals were euthanized and condyles were characterized molecularly according to aggrecan, collagen type II, and collagen type I gene expression (quantitative reverse transcriptase-polymerase chain reaction) and histologically (hematoxylin-eosin staining). Data of MSC/dexa-treated condyles were compared with untreated, dexa-treated, MSC-treated, or normal unlesioned condyles.

RESULTS

The ratio between collagen type II expression versus collagen type I expression in MSC/dexa-treated condyles was higher than one, even though the group mean value was not statistically different from that of untreated defects. Histological changes were observed between MSC/dexa-treated and untreated defects mainly in surface regularity and in hyaline matrix abundance. However, International Cartilage Repair Society score analysis did not support robust differences between those groups.

CONCLUSION

Intraarticular administration of dexamethasone after autologous MSC implantation into a preestablished full-thickness chondral defect does not contribute significantly to the regeneration of a tissue with molecular and histological characteristics identical to hyaline cartilage.

摘要

目的

本研究旨在评估在预先建立的膝关节全层软骨缺损中注射自体间充质干细胞(MSCs)后,关节内给予地塞米松对透明软骨再生的贡献。

设计

在成年雄性新西兰兔双侧股骨内侧髁上手术制造 4.5×4.5mm² 的全层软骨缺损。2 周后,将自体体外扩增的骨髓源性 MSCs 包埋于透明质酸中并植入软骨缺损。在干预后立即和每周,关节内给予地塞米松 0.25mg/kg(MSC/dexa 治疗组)。在 MSC 移植后 6 周,处死动物,根据聚集蛋白聚糖、Ⅱ型胶原和Ⅰ型胶原基因表达(定量逆转录-聚合酶链反应)和组织学(苏木精-伊红染色)对髁骨进行分子特征描述。将 MSC/dexa 治疗的髁骨的数据与未经处理、地塞米松处理、MSC 处理或正常未损伤的髁骨进行比较。

结果

尽管 MSC/dexa 治疗的髁骨中Ⅱ型胶原表达与Ⅰ型胶原表达的比值高于 1,但组平均值与未经处理的缺损并无统计学差异。在 MSC/dexa 治疗和未经处理的缺损之间观察到组织学变化,主要表现在表面规则性和透明质酸基质丰度方面。然而,国际软骨修复协会评分分析并不支持这些组之间存在显著差异。

结论

在预先建立的全层软骨缺损中注射自体 MSC 后,关节内给予地塞米松对具有与透明软骨相同的分子和组织学特征的组织再生没有显著贡献。

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