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自体间充质基质细胞固定在基于等离子体的水凝胶中,用于大型动物模型中关节软骨缺损的修复。

Autologous Mesenchymal Stromal Cells Immobilized in Plasma-Based Hydrogel for the Repair of Articular Cartilage Defects in a Large Animal Model.

机构信息

Motol University Hospital, Prague, Czech Republic.

出版信息

Physiol Res. 2023 Aug 31;72(4):485-495. doi: 10.33549/physiolres.935098.

Abstract

The treatment of cartilage defects in trauma injuries and degenerative diseases represents a challenge for orthopedists. Advanced mesenchymal stromal cell (MSC)-based therapies are currently of interest for the repair of damaged cartilage. However, an approved system for MSC delivery and maintenance in the defect is still missing. This study aimed to evaluate the effect of autologous porcine bone marrow MSCs anchored in a commercially available polyglycolic acid-hyaluronan scaffold (Chondrotissue®) using autologous blood plasma-based hydrogel in the repair of osteochondral defects in a large animal model. The osteochondral defects were induced in twenty-four minipigs with terminated skeletal growth. Eight animals were left untreated, eight were treated with Chondrotissue® and eight received Chondrotissue® loaded with MSCs. The animals were terminated 90 days after surgery. Macroscopically, the untreated defects were filled with newly formed tissue to a greater extent than in the other groups. The histological evaluations showed that the defects treated with Chondrotissue® and Chondrotissue® loaded with pBMSCs contained a higher amount of hyaline cartilage and a lower amount of connective tissue, while untreated defects contained a higher amount of connective tissue and a lower amount of hyaline cartilage. In addition, undifferentiated connective tissue was observed at the edges of defects receiving Chondrotissue® loaded with MSCs, which may indicate the extracellular matrix production by transplanted MSCs. The immunological analysis of the blood samples revealed no immune response activation by MSCs application. This study demonstrated the successful and safe immobilization of MSCs in commercially available scaffolds and defect sites for cartilage defect repair.

摘要

创伤性损伤和退行性疾病中的软骨缺损的治疗对矫形科医生来说是一个挑战。基于先进的间充质基质细胞(MSC)的治疗方法目前对于修复受损的软骨很有兴趣。然而,一种用于 MSC 递送至和维持在缺损部位的已批准系统仍然缺失。本研究旨在评估在大型动物模型中,使用自体血液衍生的基于水凝胶的聚乙二醇酸-透明质酸支架(Chondrotissue®)固定的自体猪骨髓间充质基质细胞(pBMSCs)在修复骨软骨缺损方面的效果。在已经停止骨骼生长的二十四头小型猪中诱导骨软骨缺损。八头动物未接受治疗,八头动物接受 Chondrotissue®治疗,八头动物接受负载 MSC 的 Chondrotissue®治疗。手术后 90 天处死动物。大体上,未经治疗的缺损用新形成的组织填充的程度比其他组更大。组织学评估表明,用 Chondrotissue®和负载 pBMSCs 的 Chondrotissue®治疗的缺陷包含更多的透明软骨和更少的结缔组织,而未经治疗的缺陷包含更多的结缔组织和更少的透明软骨。此外,在接受负载 MSC 的 Chondrotissue®治疗的缺陷边缘观察到未分化的结缔组织,这可能表明移植的 MSC 产生了细胞外基质。对血液样本的免疫分析表明 MSC 应用未激活免疫反应。本研究证明了在商业上可获得的支架和软骨缺损部位成功且安全地固定 MSC 以用于软骨缺损修复。

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J Tissue Eng. 2020 Aug 26;11:2041731420943839. doi: 10.1177/2041731420943839. eCollection 2020 Jan-Dec.

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