2. Academic Validation
  3. Human adipose and synovial-derived MSCs synergistically attenuate osteoarthritis by promoting chondrocyte autophagy through FoxO1 signaling

Human adipose and synovial-derived MSCs synergistically attenuate osteoarthritis by promoting chondrocyte autophagy through FoxO1 signaling

  • Stem Cell Res Ther. 2024 Aug 15;15(1):261. doi: 10.1186/s13287-024-03870-6.
Jianqun Wu 1 2,  Songqiang Huang 3,  Yangyi Yu 1 2,  Qiang Lian 1 2,  Yang Liu 4 5,  Wenfeng Dai 1 2,  Qisong Liu 1 2,  Yonghao Pan 4 5,  Gui-Ang Liu 1 2,  Kai Li 4 5,  Chao Liu 6 7,  Guangheng Li 8 9
Affiliations

Affiliations

  • 1 Division of Adult Joint Reconstruction and Sports Medicine, Department of Orthopedic Surgery, The First Affiliated Hospital (Shenzhen People's Hospital),, School of Medicine, Southern University of Science and Technology, 1017 Dongmen North Road, Luohu District, Shenzhen, 518055, China.
  • 2 Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen People's Hospital, Guangdong, China.
  • 3 School of Biomedical Sciences, Hunan University, Changsha, 410082, Hunan, China.
  • 4 Department of Biomedical Engineering, College of Engineering, Southern University of Science and Technology, 1088 Xueyuan Avenue, Nanshan District, Shenzhen, 518055, Guangdong, China.
  • 5 Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen, Guangdong, China.
  • 6 Department of Biomedical Engineering, College of Engineering, Southern University of Science and Technology, 1088 Xueyuan Avenue, Nanshan District, Shenzhen, 518055, Guangdong, China. liuc33@sustech.edu.cn.
  • 7 Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen, Guangdong, China. liuc33@sustech.edu.cn.
  • 8 Division of Adult Joint Reconstruction and Sports Medicine, Department of Orthopedic Surgery, The First Affiliated Hospital (Shenzhen People's Hospital),, School of Medicine, Southern University of Science and Technology, 1017 Dongmen North Road, Luohu District, Shenzhen, 518055, China. liguangheng@hotmail.com.
  • 9 Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen People's Hospital, Guangdong, China. liguangheng@hotmail.com.
PMID: 39148121 DOI: 10.1186/s13287-024-03870-6
Abstract

Background: Human adipose-derived stem cells (ADSCs) exert a strong anti-inflammatory effect, and synovium-derived stem cells (SDSCs) have high chondrogenic potential. Thus, this study aims to investigate whether a combination of human ADSCs and SDSCs will have a synergistic effect that will increase the chondrogenic potential of osteoarthritis (OA) chondrocytes in vitro and attenuate the cartilage degeneration of early and advanced OA in vitro.

Methods: ADSCs, SDSCs, and chondrocytes were isolated from OA patients who underwent total knee arthroplasty. The ADSCs-SDSCs mixed cell ratios were 1:0 (ADSCs only), 8:2, 5:5 (5A5S), 2:8, and 0:1 (SDSCs only). The chondrogenic potential of the OA chondrocytes was evaluated in vitro with a transwell assay or pellet culture with various mixed cell groups. The mixed cell group with the highest chondrogenic potential was then selected and injected into the knee joints of nude rats of early and advanced OA stages in vivo. The Animals were then evaluated 12 and 20 weeks after surgery through gait analysis, von frey test, microcomputed tomography, MRI, and immunohistochemical and histological analyses. Finally, the mechanisms underlying these findings were investigated through the RNA Sequencing of tissue samples in vivo and Western blot of the OA chondrocyte Autophagy pathway.

Results: Among the MSCs treatment groups, 5A5S had the greatest synergistic effect that increased the chondrogenic potential of OA chondrocytes in vitro and inhibited early and advanced OA in vivo. The 5A5S group significantly reduced cartilage degeneration, synovial inflammation, pain sensation, and nerve invasion in subchondral nude rat OA, outperforming both single-cell treatments. The underlying mechanism was the activation of chondrocyte Autophagy via the FoxO1 signaling pathway.

Conclusion: A combination of human ADSCs and SDSCs demonstrated higher potential than a single type of stem cell, demonstrating potential as a novel treatment for OA.

Keywords

Adipose-derived stem cells; Autophagy; Cartilage regeneration; Osteoarthritis; Synovium-derived stem cells.

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