Yu H, Zhang F, He YC, Zhang LS. Quality by design strategy of human mesenchymal stem/stromal cell drug products for the treatment of knee osteoarthritis. World J Stem Cells 2025; 17(5): 106547 [DOI: 10.4252/wjsc.v17.i5.106547]
Corresponding Author of This Article
Lei-Sheng Zhang, PhD, Director, Professor, National Health Commission Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, No. 204 West Donggangxi Road, Lanzhou 730000, Gansu Province, China. leisheng_zhang@163.com
Research Domain of This Article
Cell & Tissue Engineering
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. May 26, 2025; 17(5): 106547 Published online May 26, 2025. doi: 10.4252/wjsc.v17.i5.106547
Quality by design strategy of human mesenchymal stem/stromal cell drug products for the treatment of knee osteoarthritis
Hao Yu, Fan Zhang, Yi-Chen He, Lei-Sheng Zhang
Hao Yu, School of Medicine, Nankai University, Tianjin 300071, China
Fan Zhang, Faculty of Life Sciences and Medicine, Kunming University of Science and Technology, Kunming 650500, Yunnan Province, China
Yi-Chen He, Department of International, Experimental High School, Beijing Normal University, Beijing 100032, China
Lei-Sheng Zhang, National Health Commission Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
Lei-Sheng Zhang, Shandong Provincial Key Medical and Health Laboratory of Blood Ecology and Biointelligence, The Fourth People’s Hospital of Jinan Affiliated to Shandong Second Medical University, Jinan 250031, Shandong Province, China
Co-first authors: Hao Yu and Fan Zhang.
Author contributions: Yu H and Zhang F contributed equally to this work, they are co-first authors of this manuscript; Yu H, Zhang F, and He YC conducted the data analyses and interpretation, manuscript writing, and revision; Yu H, Zhang F, and Zhang LS conceived and designed the study, and gave final approval of the manuscript. All authors have read and approved the publication of the manuscript.
Supported by Taishan Scholar Special Funding, No. tsqnz20240858; Medical and Health Technology Project of Shandong Province, No. 202402050122; Science and Technology Development Plan of Jinan Municipal Health Commission, No. 2024301008; Clinical Medical Science and Technology Innovation Program of Jinan Science and Technology Bureau, No. 202430055; Natural Science Foundation of Jiangxi Province, No. 20224BAB206077; Jiangxi Provincial Leading Talent of “Double Thousand Plan”, No. jxsq2023102017; Gansu Provincial Hospital Intra-Hospital Research Fund Project, No. 22GSSYB-6; and the 2022 Master/Doctor/Postdoctoral Program of National Health Commission Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, No. NHCDP2022004 and No. NHCDP2022008.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lei-Sheng Zhang, PhD, Director, Professor, National Health Commission Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, No. 204 West Donggangxi Road, Lanzhou 730000, Gansu Province, China. leisheng_zhang@163.com
Received: March 3, 2025 Revised: April 1, 2025 Accepted: May 7, 2025 Published online: May 26, 2025 Processing time: 85 Days and 3.4 Hours
Abstract
Knee osteoarthritis (KOA), characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder, is one of the leading causes of disability worldwide, which has become a high burden due to the multifactorial nature and the deficiency of available disease-modifying treatments. The application of mesenchymal stem/stromal cells (MSCs) as therapeutic drugs has provided novel treatment options for diverse degenerative and chronic diseases including KOA. However, the complexity and specificity of the “live” cells have posed challenges for MSC-based drug development and the concomitant scale-up preparation from laboratory to industrialization. For instance, despite the considerable progress in ex vivo cell culture technology for fulfilling the robust development of drug conversion and clinical trials, yet significant challenges remain in obtaining regulatory approvals. Thus, there’s an urgent need for the research and development of MSC drugs for KOA. In this review, we provide alternative solution strategies for the preparation of MSC drugs on the basis of the principle of quality by design, including designing the cell production processes, quality control, and clinical applications. In detail, we mainly focus on the quality by design method for MSC manufacturing in standard cell-culturing factories for the treatment of KOA by using the Quality Target Product Profile as a starting point to determine potential critical quality attributes and to establish relationships between critical material attributes and critical process parameters. Collectively, this review aims to meet product performance and robust process design, and should help to reduce the gap between compliant products and the production of compliant good manufacturing practice.
Core Tip: Knee osteoarthritis is one of the leading causes of disability worldwide and has become a high burden due to the multifactorial nature and the deficiency of available disease-modifying treatments. Herein, we review the state-of-the-art literatures of the quality by design strategy of mesenchymal stem/stromal cell drug products for knee osteoarthritis treatment, together with discuss the accompanied principles as well, which will collectively help to reduce the gap between compliant products and the production of compliant good manufacturing practice.
