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Cartilage fragments combined with BMSCs-Derived exosomes can promote tendon-bone healing after ACL reconstruction.

ABSTRACT: Anterior cruciate ligament reconstruction (ACLR) often fails due to the inability of tendon-bone integration to regenerate normal tissues and formation of fibrous scar tissues in the tendon-bone interface. Cartilage fragments and exosomes derived from bone mesenchymal stromal cells (BMSCs-Exos) can enhance enthesis healing. Nevertheless, the effects on the tendon-bone healing of ACLR remain unknown. This study found that BMSCs-Exos can promote the proliferation of chondrocytes in cartilage fragments, and activated the expression of chondro-related genes SOX9 and Aggrecan. The optimal effect concentration was 10¹² events/uL. Besides, BMSCs-Exos could significantly upregulated the expression of BMP7 and Smad5 in cartilage fragments, and further enhanced the expression of chondrogenic genes. Moreover, this study established a rat model of ACLR and implanted the BMSCs-Exos/cartilage fragment complex into the femoral bone tunnel. Results demonstrated that the mean diameters of the femoral bone tunnels were significantly smaller in the BE-CF group than those in the CF group (p = 0.038) and control group (p = 0.007) at 8 weeks after surgery. Besides, more new bone formation was observed in the femoral tunnels in the BE-CF group, as demonstrated by a larger BV/TV ratio based on the reconstructed CT scans. Histological results also revealed the regeneration of tendon-bone structures, especially fibrocartilage. Thus, these findings provide a promising result that BMSCs-Exos/cartilage fragment complex can prevent the enlargement of bone tunnel and promote tendon-bone healing after ACLR, which may have resulted from the regulation of the BMP7/Smad5 signaling axis.

SUBMITTER: Zhang C

PROVIDER: S-EPMC10550801 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Cartilage fragments combined with BMSCs-Derived exosomes can promote tendon-bone healing after ACL reconstruction.

Zhang Chi C Jiang Chao C Jin Jiale J Lei Pengfei P Cai Youzhi Y Wang Yue Y

Materials today. Bio 20230926

Anterior cruciate ligament reconstruction (ACLR) often fails due to the inability of tendon-bone integration to regenerate normal tissues and formation of fibrous scar tissues in the tendon-bone interface. Cartilage fragments and exosomes derived from bone mesenchymal stromal cells (BMSCs-Exos) can enhance enthesis healing. Nevertheless, the effects on the tendon-bone healing of ACLR remain unknown. This study found that BMSCs-Exos can promote the proliferation of chondrocytes in cartilage fragm ...[more]

PMID: 37810754

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Project description:BackgroundBone formation plays an important role in early tendon-bone healing after anterior cruciate ligament reconstruction (ACLR). Dedifferentiated osteogenic bone marrow mesenchymal stem cells (De-BMSCs) have enhanced osteogenic potential. This study aimed to investigate the effect of De-BMSCs transplantation on the promotion of bone formation at the tendon-bone interface after ACLR and to further explore the molecular mechanism of the enhanced osteogenic potential of De-BMSCs.MethodsBMSCs from the femurs and tibias of New Zealand white rabbits were subjected to osteogenic induction and then cultured in medium without osteogenic factors; the obtained cell population was termed De-BMSCs. De-BMSCs were induced to undergo osteo-, chondro- and adipo-differentiation in vitro to examine the characteristics of primitive stem cells. An ACLR model with a semitendinosus tendon was established in rabbits, and the animals were divided into a control group, BMSCs group, and De-BMSCs group. At 12 weeks after surgery, the rabbits in each group were sacrificed to evaluate tendon-bone healing by histologic staining, micro-computed tomography (micro-CT) examination, and biomechanical testing. During osteogenic differentiation of De-BMSCs, an siRNA targeting nuclear factor of activated T-cells 1 (NFATc1) was used to verify the molecular mechanism of the enhanced osteogenic potential of De-BMSCs.ResultsDe-BMSCs exhibited some properties similar to BMSCs, including multiple differentiation potential and cell surface markers. Bone formation at the tendon-bone interface in the De-BMSCs group was significantly increased, and biomechanical strength was significantly improved. During the osteogenic differentiation of De-BMSCs, the expression of Nanog and NFATc1 was synergistically increased, which promoted the interaction of NFATc1 and Osterix, resulting in increased expression of osteoblast marker genes such as COL1A, OCN, and OPN.ConclusionsDe-BMSCs transplantation could promote bone formation at the tendon-bone interface after ACLR and improve the biomechanical strength of the reconstruction. The Nanog/NFATc1/Osterix signaling pathway mediated the enhanced osteogenic differentiation efficiency of De-BMSCs.

Project description:Background/Objectives: The optimal graft, particularly in combined anterior cruciate ligament (ACL) and medial collateral ligament (MCL) injuries, remains controversial. We evaluated the influence of graft choice between bone-patellar tendon-bone (BPTB) and hamstring autografts on clinical outcomes in combined ACL and MCL injuries. Methods: This retrospective analysis included patients with concurrent ACL and MCL injuries who underwent single-bundle ACL reconstruction with BPTB (group B) or hamstring (group H) grafts, between 2010 and 2019, with a ≥2-year follow-up. Patients were classified based on the MCL injury grade (I, II, or III). Clinical outcomes were assessed through knee stability evaluations using valgus stress radiographs and the KT-2000 arthrometer, patient-reported outcomes using the International Knee Documentation Committee (IKDC) subjective score and Lysholm score, and radiologic outcomes using the IKDC radiographic grade. Results: The study included 169 patients (group B, 92; group H, 77). No significant between-group differences in knee stability or functional outcomes were found after follow-up. Within the same MCL injury grade, particularly in high-grade MCL injuries, BPTB grafts resulted in significantly better medial stability (side-to-side difference in medial joint opening on valgus stress radiographs: grade II, p = 0.006; grade III, p = 0.039) and functional outcomes (IKDC subjective score: grade II, p = 0.045; grade III, p = 0.038) than hamstring grafts. In the hamstring group, higher-grade MCL injuries were associated with worse outcomes (Lysholm knee score, p = 0.009; IKDC subjective score, p = 0.015). Conclusions: Graft choice in ACL reconstruction with concomitant MCL injuries may affect clinical outcomes, particularly in high-grade MCL injuries. Although both graft types performed similarly overall, BPTB grafts provided superior medial stability and functional results in higher-grade MCL injuries. However, caution is needed when interpreting these results due to limitations such as the small sample size and the lack of randomization in graft selection.

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Cartilage fragments combined with BMSCs-Derived exosomes can promote tendon-bone healing after ACL reconstruction.

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Cartilage fragments combined with BMSCs-Derived exosomes can promote tendon-bone healing after ACL reconstruction.

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