Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Improve Ligament–Bone Integration After Anterior Cruciate Ligament Primary Repair in Rabbit

Biomolecules, vol. 15, pp. 396

Abstract

BACKGROUNDS: In this research, we want to find out whether extracellular vesicles (EVs) from adipose-derived mesenchymal stem cells (MSCs) can improve ligament-bone integration after primary Anterior Cruciate Ligament (ACL) repair by performing immunological and biomechanical tests. METHODS: All of the rabbits underwent ACL resection at the proximal attachment to the femur bone, and then were divided into four groups. We performed an ELISA examination from the tissue at the bone-ligament interface of iNOS, CD206, MMP-3, and TIMP-1 to evaluate their levels at the inflammatory stage at the end of the first week. Immunoexpression of type I and III collagen and failure load biomechanical tests were performed at the end of the sixth week. RESULT: The group that underwent ACL repair with EVs augmentation had significantly higher levels of CD206, significantly lower MMP-3 levels, and significantly higher TIMP-1 levels in the first week. The iNOS levels in the group that underwent ACL repair with EVs augmentation were significantly different compared to the control group that did not receive any. The number of type I collagen fibers and the failure load levels in the group that underwent ACL repair with EVs augmentation were significantly higher. CONCLUSIONS: EVs from adipose-derived MSCs can improve the outcome of primary ACL repair in rabbits by regulating the inflammatory process during the healing period.

Authors 7

1. Andre Yanuar

   Padjadjaran University

   Affiliation as printed

   Department of Orthopaedic and Traumatology, Santo Borromeus Hospital, Bandung 40132, Indonesia

   Doctoral Program, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia

2. Hasrayati Agustina

   Padjadjaran University · Dr. Hasan Sadikin General Hospital

   Affiliation as printed

   Department of Pathology Anatomy, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung 40161, Indonesia

3. Radiana Dhewayani Antarianto

   University of Indonesia

   Affiliation as printed

   Department of Histology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia

   Stem Cell and Tissue Engineering Research Cluster, Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia

4. Andi Isra Mahyuddin

   Bandung Institute of Technology

   Affiliation as printed

   Faculty of Mechanical and Aerospace Engineering, Institut Teknologi Bandung (ITB), Bandung 40132, Indonesia

5. Ismail Hadisoebroto Dilogo

   University of Indonesia · Rumah Sakit Umum Pusat Nasional Dr. Cipto Mangunkusumo

   Affiliation as printed

   Department of Orthopaedics and Traumatology, Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo General Hospital, Jakarta 10430, Indonesia

   Stem Cell Integrated Medical Technology Service Unit, Faculty of Medicine, Universitas Indonesia/ipto Mangunkusumo General Hospital, Jakarta 10430, Indonesia

   Stem Cell and Tissue Engineering Research Cluster, Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia

6. Nicolaas Cyrillus Budhiparama Aachen Department of Orthopaedics, Leiden University Medical Center

   Leiden University · Leiden University Medical Center · Universitas Airlangga

   Affiliation as printed

   Department of Orthopaedic and Traumatology, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia

   Department of Orthopaedics, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands

7. Nur Atik corresponding

   Padjadjaran University

   Affiliation as printed

   Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia

   Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung 40131, Indonesia