Department of Bioengineering and IBB - Institute for Biotechnology and Bioengineering - Instituto Superior Técnico IST, Technical University of Lisbon, Lisboa, Portugal.
Biotechnol J. 2013 Jun;8(6):644-54. doi: 10.1002/biot.201200373. Epub 2013 Apr 26.
The many clinical trials currently in progress will likely lead to the widespread use of stem cell-based therapies for an extensive variety of diseases, either in autologous or allogeneic settings. With the current pace of progress, in a few years' time, the field of stem cell-based therapy should be able to respond to the market demand for safe, robust and clinically efficient stem cell-based therapeutics. Due to the limited number of stem cells that can be obtained from a single donor, one of the major challenges on the roadmap for regulatory approval of such medicinal products is the expansion of stem cells using Good Manufacturing Practices (GMP)-compliant culture systems. In fact, manufacturing costs, which include production and quality control procedures, may be the main hurdle for developing cost-effective stem cell therapies. Bioreactors provide a viable alternative to the traditional static culture systems in that bioreactors provide the required scalability, incorporate monitoring and control tools, and possess the operational flexibility to be adapted to the differing requirements imposed by various clinical applications. Bioreactor systems face a number of issues when incorporated into stem cell expansion protocols, both during development at the research level and when bioreactors are used in on-going clinical trials. This review provides an overview of the issues that must be confronted during the development of GMP-compliant bioreactors systems used to support the various clinical applications employing stem cells.
目前正在进行的许多临床试验可能会导致基于干细胞的疗法在自体或同种异体环境中广泛用于治疗各种疾病。随着目前进展的步伐，在几年内，基于干细胞的治疗领域应该能够满足市场对安全、强大和临床有效的基于干细胞的治疗的需求。由于从单个供体中获得的干细胞数量有限，因此此类药物监管批准路线图上的主要挑战之一是使用符合良好生产规范 (GMP) 的培养系统来扩增干细胞。事实上，包括生产和质量控制程序在内的制造成本可能是开发具有成本效益的干细胞疗法的主要障碍。生物反应器为传统的静态培养系统提供了一种可行的替代方案，因为生物反应器提供了所需的可扩展性，整合了监测和控制工具，并具有操作灵活性，可以适应各种临床应用所施加的不同要求。在将生物反应器系统纳入干细胞扩增方案时，无论是在研究层面的开发阶段还是在生物反应器用于正在进行的临床试验时，都会面临许多问题。本综述概述了在开发用于支持使用干细胞的各种临床应用的符合 GMP 的生物反应器系统时必须面对的问题。
