Andrade Pedro Z, dos Santos Francisco, Cabral Joaquim M S, da Silva Cláudia L
Department of Bioengineering and Institute for Biotechnology and Bioengineering (IBB), Instituto Superior Técnico, Lisboa, Portugal.
Cell2b, Advanced Therapeutics, Biocant Park, Cantanhede, Portugal.
J Tissue Eng Regen Med. 2015 Sep;9(9):988-1003. doi: 10.1002/term.1741. Epub 2013 Apr 8.
Umbilical cord blood (UCB) transplantation has observed a significant increase in recent years, due to the unique features of UCB haematopoietic stem/progenitor cells (HSCs) for the treatment of blood-related disorders. However, the low cell numbers available per UCB unit significantly impairs the widespread use of this source for transplantation of adult patients, resulting in graft failure, delayed engraftment and delayed immune reconstitution. In order to overcome this issue, distinct approaches are now being considered in clinical trials, such as double-UCB transplantation, intrabone injection or ex vivo expansion. In this article the authors review the current state of the art, future trends and challenges on the ex vivo expansion of UCB HSCs, focusing on culture parameters affecting the yield and quality of the expanded HSC grafts: novel HSC selection schemes prior to cell culture, cytokine/growth factor cocktails, the impact of biochemical factors (e.g. O2 ) or the addition of supportive cells, e.g. mesenchymal stem/stromal cell (MSC)-based feeder layers) were addressed. Importantly, a critical challenge in cellular therapy is still the scalability, reproducibility and control of the expansion process, in order to meet the clinical requirements for therapeutic applications. Efficient design of bioreactor systems and operation modes are now the focus of many bioengineers, integrating the increasing 'know-how' on HSC biology and physiology, while complying with the GMP standards for the production of cellular products, i.e. through the use of commercially available, highly controlled, disposable technologies.
近年来，由于脐带血（UCB）造血干/祖细胞（HSCs）在治疗血液相关疾病方面具有独特特性，脐带血移植数量显著增加。然而，每个UCB单位可获得的细胞数量较少，这严重阻碍了该来源在成年患者移植中的广泛应用，导致移植失败、植入延迟和免疫重建延迟。为了克服这一问题，目前临床试验正在考虑采用不同方法，如双脐带血移植、骨内注射或体外扩增。在本文中，作者回顾了脐带血造血干细胞体外扩增的当前技术水平、未来趋势和挑战，重点关注影响扩增后的造血干细胞移植物产量和质量的培养参数：细胞培养前的新型造血干细胞选择方案、细胞因子/生长因子组合、生化因素（如氧气）的影响或添加支持细胞（如基于间充质干/基质细胞（MSC）的饲养层）。重要的是，细胞治疗中的一个关键挑战仍然是扩增过程的可扩展性、可重复性和可控性，以满足治疗应用的临床要求。生物反应器系统和操作模式的高效设计现在是许多生物工程师关注的焦点，他们将日益增长的造血干细胞生物学和生理学知识融入其中，同时遵守细胞产品生产的GMP标准，即通过使用市售的、高度可控的一次性技术。
