Titova Maria, Popova Elena, Nosov Alexander
K.A. Timiryazev Institute of Plant Physiology, Russian Academy of Sciences, 127276 Moscow, Russia.
Department of Biology, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia.
Plants (Basel). 2024 Feb 1;13(3):430. doi: 10.3390/plants13030430.
The cultivation of plant cells in large-scale bioreactor systems has long been considered a promising alternative for the overexploitation of wild plants as a source of bioactive phytochemicals. This idea, however, faced multiple constraints upon realization, resulting in very few examples of technologically feasible and economically effective biotechnological companies. The bioreactor cultivation of plant cells is challenging. Even well-growing and highly biosynthetically potent cell lines require a thorough optimization of cultivation parameters when upscaling the cultivation process from laboratory to industrial volumes. The optimization includes, but is not limited to, the bioreactor's shape and design, cultivation regime (batch, fed-batch, continuous, semi-continuous), aeration, homogenization, anti-foaming measures, etc., while maintaining a high biomass and metabolite production. Based on the literature data and our experience, the cell cultures often demonstrate cell line- or species-specific responses to parameter changes, with the dissolved oxygen concentration (pO) and shear stress caused by stirring being frequent growth-limiting factors. The mass transfer coefficient also plays a vital role in upscaling the cultivation process from smaller to larger volumes. The Experimental Biotechnological Facility at the K.A. Timiryazev Institute of Plant Physiology has operated since the 1970s and currently hosts a cascade of bioreactors from the laboratory (20 L) to the pilot (75 L) and a semi-industrial volume (630 L) adapted for the cultivation of plant cells. In this review, we discuss the most appealing cases of the cell cultivation process's adaptation to bioreactor conditions featuring the cell cultures of medicinal plants Wall. ex Griseb., Zucc., (Roxb.) Miers, (T. Nees) C.A.Mey., (C. Moore ex E. Fourn.) L.H. Bailey, and L. Harms. The results of cell cultivation in bioreactors of different types and designs using various cultivation regimes are covered and compared with the literature data. We also discuss the role of the critical factors affecting cell behavior in bioreactors with large volumes.
长期以来，在大规模生物反应器系统中培养植物细胞一直被视为一种有前景的替代方法，以避免过度开发野生植物作为生物活性植物化学物质的来源。然而，这一想法在实施过程中面临多重限制，导致技术上可行且经济有效的生物技术公司实例极少。植物细胞的生物反应器培养具有挑战性。即使是生长良好且生物合成能力很强的细胞系，在将培养过程从实验室规模扩大到工业规模时，也需要对培养参数进行全面优化。这种优化包括但不限于生物反应器的形状和设计、培养方式（分批、补料分批、连续、半连续）、通气、均质化、消泡措施等，同时要保持高生物量和代谢产物产量。根据文献数据和我们的经验，细胞培养物对参数变化往往表现出细胞系或物种特异性反应，溶解氧浓度（pO）和搅拌引起的剪切应力常常是生长限制因素。传质系数在将培养过程从小规模扩大到大规模时也起着至关重要的作用。自20世纪70年代以来，K.A.季米里亚泽夫植物生理研究所的实验生物技术设施一直在运行，目前拥有一系列从实验室规模（20升）到中试规模（75升）以及半工业规模（630升）的生物反应器，适用于植物细胞培养。在这篇综述中，我们讨论了药用植物Wall. ex Griseb.、Zucc.、(Roxb.) Miers、(T. Nees) C.A.Mey.、(C. Moore ex E. Fourn.) L.H. Bailey和L. Harms的细胞培养物适应生物反应器条件的最具吸引力的案例。涵盖了使用不同培养方式在不同类型和设计的生物反应器中进行细胞培养的结果，并与文献数据进行了比较。我们还讨论了影响大规模生物反应器中细胞行为的关键因素的作用。
