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  3. Immunity-and-matrix-regulatory cells enhance cartilage regeneration for meniscus injuries: a phase I dose-escalation trial

Immunity-and-matrix-regulatory cells enhance cartilage regeneration for meniscus injuries: a phase I dose-escalation trial

  • Signal Transduct Target Ther. 2023 Nov 1;8(1):417. doi: 10.1038/s41392-023-01670-7.
Liangjiang Huang # 1,  Song Zhang # 1,  Jun Wu # 2 3,  Baojie Guo # 2,  Tingting Gao 2,  Sayed Zulfiqar Ali Shah 1,  Bo Huang 4,  Yajie Li 1 5,  Bo Zhu 6,  Jiaqi Fan 3,  Liu Wang 2 3 7,  Yani Xiao 8,  Wenjing Liu 2,  Yao Tian 2,  Zhengyu Fang 1,  Yingying Lv 1,  Lingfeng Xie 1,  Sheng Yao 1,  Gaotan Ke 4,  Xiaolin Huang 1,  Ying Huang 8,  Yujuan Li 9,  Yi Jia 9,  Zhongwen Li 2 3,  Guihai Feng 2 3 7,  Yan Huo 8,  Wei Li 2 3 7,  Qi Zhou 2 3 7,  Jie Hao 10 11 12,  Baoyang Hu 13 14 15,  Hong Chen 16 17
Affiliations

Affiliations

  • 1 Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 National Stem Cell Resource Center, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
  • 3 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
  • 4 Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Stem Cell Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 6 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 7 University of Chinese Academy of Sciences, Beijing, China.
  • 8 Beijing Key Lab for Pre-clinical Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, China.
  • 9 Beijing Zephyrm Biotechnologies Co., Ltd., Beijing, China.
  • 10 National Stem Cell Resource Center, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. haojie@ioz.ac.cn.
  • 11 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. haojie@ioz.ac.cn.
  • 12 University of Chinese Academy of Sciences, Beijing, China. haojie@ioz.ac.cn.
  • 13 National Stem Cell Resource Center, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. byhu@ioz.ac.cn.
  • 14 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. byhu@ioz.ac.cn.
  • 15 University of Chinese Academy of Sciences, Beijing, China. byhu@ioz.ac.cn.
  • 16 Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. chenhong1129@hust.edu.cn.
  • 17 Stem Cell Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. chenhong1129@hust.edu.cn.
  • # Contributed equally.
PMID: 37907503 DOI: 10.1038/s41392-023-01670-7
Abstract

Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

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