BMP-2/TGF-β1 gene insertion into ligament-derived stem cells sheet promotes tendon-bone healing in a mouse

被引：6
作者：
Wei, Bing [1 ,2 ]
Li, Zhuang [1 ,2 ]
Lin, Yucheng [1 ,2 ]
Hu, Xinyue [1 ,2 ]
Xu, Li [1 ,2 ]
Wang, Shanzheng [1 ,2 ]
Ji, Mingliang [1 ,2 ]
Lu, Jun [1 ,2 ,3 ]
机构：
[1] Southeast Univ, Sch Med, Nanjing, Jiangsu, Peoples R China
[2] Southeast Univ, Zhongda Hosp, Joint & Sports Med Ctr, Dept Orthopaed Surg, Nanjing, Jiangsu, Peoples R China
[3] Southeast Univ, Zhongda Hosp, Sch Med, 87 Dingjiaqiao Rd, Nanjing 210009, Jiangsu, Peoples R China
来源：
BIOTECHNOLOGY JOURNAL | 2023年 / 18卷 / 05期
基金：
中国国家自然科学基金;
关键词：
anterior cruciate ligament (ACL)-derived stem cells; anterior cruciate ligament reconstruction; bone morphogenetic protein-2; differentiation; tendon-bone healing; transforming growth factor-beta 1;
D O I：
10.1002/biot.202200470
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
Bone morphogenetic protein-2 (BMP-2) and transforming growth factor-beta 1 (c) reportedly induce the osteogenic and tenogenic differentiation of anterior cruciate ligament (ACL)-derived stem cells (LDSCs), respectively. However, few studies have investigated the effect of BMP-2/TGF-beta 1 on the differentiation of LDSC. We developed a BMP-2/TGF-beta 1 gene insertion into an LDSC cell sheet that promotes tendon-bone healing in a mouse ACL reconstruction (ACLR) model.CD34(+) LDSCs were isolated from human ACL stump tissues, virally transduced to express BMP-2 or TGF-beta 1, and then embedded within cell sheets. All mice underwent ACLR using an autograft wrapped with a cell sheet and were randomly divided into three groups: BMP-2-, TGF-beta 1-, and BMP-2/TGF-beta 1-transduced. At 4 and 8 weeks, tendon-bone healing was evaluated by micro-CT, biomechanical test, and histological analysis. BMP-2 and TGF-beta 1 promoted the osteogenic and tenogenic differentiation of LDSC in vitro. BMP-2/TGF-beta 1-transduced LDSC sheet application contributed to early improvement in mean failure load and graft stiffness, accelerated maturation of the tendon-bone junction, and inhibited bone tunnel widening. Furthermore, reduced M1 macrophage infiltration and a higher M2 macrophage percentage were observed in the BMP-2/TGF-beta 1-transduced LDSC group.This work demonstrated that BMP-2 and TGF-beta 1 promoted CD34(+) LDSCs osteogenic and tenogenic differentiation in vitro and in vivo, which accelerated the tendon-bone healing after ACLR using autografts wrapped with cell sheets in a mouse model.
引用
收藏
页数：12
相关论文
共 37 条
  • [1] Cherniavskii A M, 2008, Angiol Sosud Khir, V14, P133
  • [2] Long-Term Failure of Anterior Cruciate Ligament Reconstruction
    Crawford, S. Nicholas
    Waterman, Brian R.
    Lubowitz, James H.
    [J]. ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY, 2013, 29 (09) : 1566 - 1571
  • [3] Immobilization Modulates Macrophage Accumulation in Tendon-Bone Healing
    Dagher, Elias
    Hays, Peyton L.
    Kawamura, Sumito
    Godin, Jon
    Deng, Xiang-hua
    Rodeo, Scott A.
    [J]. CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 2009, 467 (01) : 281 - 287
  • [4] Artificial cell membrane binding thrombin constructs drive in situ fibrin hydrogel formation
    Deller, Robert C.
    Richardson, Thomas
    Richardson, Rebecca
    Bevan, Laura
    Zampetakis, Ioannis
    Scarpa, Fabrizio
    Perriman, Adam W.
    [J]. NATURE COMMUNICATIONS, 2019, 10 (1)
  • [5] Enhancement of Tendon-Bone Healing for Anterior Cruciate Ligament (ACL) Reconstruction Using Bone Marrow-Derived Mesenchymal Stem Cells Infected with BMP-2
    Dong, Yu
    Zhang, Qingguo
    Li, Yunxia
    Jiang, Jia
    Chen, Shiyi
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2012, 13 (10): : 13605 - 13620
  • [6] MFG-E8 promotes tendon-bone healing by regualting macrophage efferocytosis and M2 polarization after anterior cruciate ligament reconstruction
    Geng, Rui
    Lin, Yucheng
    Ji, Mingliang
    Chang, Qing
    Li, Zhuang
    Xu, Li
    Zhang, Weituo
    Lu, Jun
    [J]. JOURNAL OF ORTHOPAEDIC TRANSLATION, 2022, 34 : 11 - 21
  • [7] RETRACTED: Exosome-delivered BMP-2 and polyaspartic acid promotes tendon bone healing in rotator cuff tear via Smad/RUNX2 signaling pathway (Retracted Article)
    Han, Lei
    Liu, Hong
    Fu, Huajun
    Hu, Yugen
    Fang, Weili
    Liu, Junsheng
    [J]. BIOENGINEERED, 2022, 13 (01) : 1459 - 1475
  • [8] Tumor necrosis factor-α and transforming growth factor-β1 facilitate differentiation and proliferation of tendon-derived stem cells in vitro
    Han, Peilin
    Cui, Qingbo
    Yang, Shulong
    Wang, Hao
    Gao, Peng
    Li, Zhaozhu
    [J]. BIOTECHNOLOGY LETTERS, 2017, 39 (05) : 711 - 719
  • [9] Mesenchymal stromal cells and platelet-rich plasma promote tendon allograft healing in ovine anterior cruciate ligament reconstruction
    Hexter, Adam T.
    Sanghani-Kerai, Anita
    Heidari, Nima
    Kalaskar, Deepak M.
    Boyd, Ashleigh
    Pendegrass, Catherine
    Rodeo, Scott A.
    Haddad, Fares S.
    Blunn, Gordon W.
    [J]. KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY, 2021, 29 (11) : 3678 - 3688
  • [10] Bone marrow mesenchymal stem cell-derived exosomes promote rotator cuff tendon-bone healing by promoting angiogenesis and regulating M1 macrophages in rats
    Huang, Yao
    He, Bing
    Wang, Lei
    Yuan, Bin
    Shu, Hao
    Zhang, Fucheng
    Sun, Luning
    [J]. STEM CELL RESEARCH & THERAPY, 2020, 11 (01)
1234