Cartilage regeneration and inflammation modulation in knee osteoarthritis following injection of allogeneic adipose-derived mesenchymal stromal cells: a phase II, triple-blinded, placebo controlled, randomized trial

Stem Cell Research & Therapy

Research

Mohammad Hassanzadeh¹  Mehdi Mohammadpour¹  Abolfazl Bagherifard¹  Javad Mohammadi²  Mehdi Alikhani³  Massoud Vosough³  Bahareh Sadri³  Hoda Madani³  Shahedeh Karimi³  Kasra Moeinabadi-Bidgoli³  Dylana Diaz-Solano⁴  Mohammad Mehrazmay⁵ 

[1] Bone and Joint Reconstruction Research Center, Department of Orthopedics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran;Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;Unidad de Terapia Celular - Laboratorio de Patología Celular y Molecular, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 21827, 1020-A, Caracas, Venezuela;Shahid Beheshti University of Medical Sciences, Tehran, Iran;

关键词: Mesenchymal stromal cells;    Knee osteoarthritis;    Cell-based therapy;    Regenerative medicine;    Cartilage regeneration;    Liquid biomarkers;   

DOI  :  10.1186/s13287-023-03359-8

 received in 2022-11-19, accepted in 2023-04-28,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundIntra-articular injection of mesenchymal stromal cells (MSCs) with immunomodulatory features and their paracrine secretion of regenerative factors proposed a noninvasive therapeutic modality for cartilage regeneration in knee osteoarthritis (KOA).MethodsTotal number of 40 patients with KOA enrolled in two groups. Twenty patients received intra-articular injection of 100 × 106 allogeneic adipose-derived mesenchymal stromal cells (AD-MSCs), and 20 patients as control group received placebo (normal saline). Questionnaire-based measurements, certain serum biomarkers, and some cell surface markers were evaluated for 1 year. Magnetic resonance imaging (MRI) before and 1 year after injection was performed to measure possible changes in the articular cartilage.ResultsForty patients allocated including 4 men (10%) and 36 women (90%) with average age of 56.1 ± 7.2 years in control group and 52.8 ± 7.5 years in AD-MSCs group. Four patients (two patients from AD-MSCs group and two patients from the control group) excluded during the study. Clinical outcome measures showed improvement in AD-MSCs group. Hyaluronic acid and cartilage oligomeric matrix protein levels in blood serum decreased significantly in patients who received AD-MSCs (P < 0.05). Although IL-10 level significantly increased after 1 week (P < 0.05), the serum level of inflammatory markers dramatically decreased after 3 months (P < 0.001). Expressions of CD3, CD4, and CD8 have a decreasing trend during 6-month follow-up (P < 0.05), (P < 0.001), and (P < 0.001), respectively. However, the number of CD25+ cells increased remarkably in the treatment group 3 months after intervention (P < 0.005). MRI findings showed a slight increase in the thickness of tibial and femoral articular cartilages in AD-MSCs group. The changes were significant in the medial posterior and medial anterior areas of ​​the tibia with P < 0.01 and P < 0.05, respectively.ConclusionInter-articular injection of AD-MSCs in patients with KOA is safe. Laboratory data, MRI findings, and clinical examination of patients at different time points showed notable articular cartilage regeneration and significant improvement in the treatment group.Trial registration: Iranian registry of clinical trials (IRCT, https://en.irct.ir/trial/46), IRCT20080728001031N23. Registered 24 April 2018.

【 授权许可】

CC BY   
© The Author(s) 2023

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