دورية أكاديمية
A GMP-compliant manufacturing method for Wharton’s jelly-derived mesenchymal stromal cells
| العنوان: | A GMP-compliant manufacturing method for Wharton’s jelly-derived mesenchymal stromal cells |
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| المؤلفون: | Wanglong Chu, Fen Zhang, Xiuping Zeng, Fangtao He, Guanyan Shang, Tao Guo, Qingfang Wang, Jianfu Wu, Tongjing Li, Zhen Zhong Zhong, Xiao Liang, Junyuan Hu, Muyun Liu |
| المصدر: | Stem Cell Research & Therapy, Vol 15, Iss 1, Pp 1-19 (2024) |
| بيانات النشر: | BMC, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine (General) LCC:Biochemistry |
| مصطلحات موضوعية: | Enzymatic digestion, Good manufacturing practice, Mesenchymal stem cells, Scale-up, Stability, Wharton jelly, Medicine (General), R5-920, Biochemistry, QD415-436 |
| الوصف: | Abstract Background Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) hold great therapeutic potential in regenerative medicine. Therefore, it is crucial to establish a Good Manufacturing Practice (GMP)-compliant methodology for the isolation and culture of WJ-MSCs. Through comprehensive research, encompassing laboratory-scale experiments to pilot-scale studies, we aimed to develop standardized protocols ensuring the high yield and quality of WJ-MSCs manufacturing. Methods Firstly, optimization of parameters for the enzymatic digestion method used to isolate WJ-MSCs was conducted. These parameters included enzyme concentrations, digestion times, seeding densities, and culture media. Additionally, a comparative analysis between the explant method and the enzymatic digestion method was performed. Subsequently, the consecutive passaging of WJ-MSCs, specifically up to passage 9, was evaluated using the optimized method. Finally, manufacturing processes were developed and scaled up, starting from laboratory-scale flask-based production and progressing to pilot-scale cell factory-based production. Furthermore, a stability study was carried out to assess the storage and use of drug products (DPs). Results The optimal parameters for the enzymatic digestion method were a concentration of 0.4 PZ U/mL Collagenase NB6 and a digestion time of 3 h, resulting in a higher yield of P0 WJ-MSCs. In addition, a positive correlation between the weight of umbilical cord tissue and the quantities of P0 WJ-MSCs has been observed. Evaluation of different concentrations of human platelet lysate revealed that 2% and 5% concentrations resulted in similar levels of cell expansion. Comparative analysis revealed that the enzymatic digestion method exhibited faster outgrowth of WJ-MSCs compared to the explant method during the initial passage. Passages 2 to 5 exhibited higher viability and proliferation ability throughout consecutive passaging. Moreover, scalable manufacturing processes from the laboratory scale to the pilot scale were successfully developed, ensuring the production of high-quality WJ-MSCs. Multiple freeze-thaw cycles of the DPs led to reduced cell viability and viable cell concentration. Subsequent thawing and dilution of the DPs resulted in a significant decrease in both metrics, especially when stored at 20–27 °C. Conclusion This study offers valuable insights into optimizing the isolation and culture of WJ-MSCs. Our scalable manufacturing processes facilitate the large-scale production of high-quality WJ-MSCs. These findings contribute to the advancement of WJ-MSCs-based therapies in regenerative medicine. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-6512 |
| Relation: | https://doaj.org/toc/1757-6512 |
| DOI: | 10.1186/s13287-024-03725-0 |
| URL الوصول: | https://doaj.org/article/fa2869ca4b3c4ab18e67e923bf6092b4 |
| رقم الأكسشن: | edsdoj.fa2869ca4b3c4ab18e67e923bf6092b4 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 17576512 |
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| DOI: | 10.1186/s13287-024-03725-0 |