Sandvig Ioanna, Gadjanski Ivana, Vlaski-Lafarge Marija, Buzanska Leonora, Loncaric Darija, Sarnowska Ana, Rodriguez Laura, Sandvig Axel, Ivanovic Zoran
1 Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway .
2 Innovation Center, Faculty of Mechanical Engineering, University of Belgrade , Belgrade, Serbia .
Stem Cells Dev. 2017 Apr 15;26(8):554-565. doi: 10.1089/scd.2016.0268. Epub 2017 Jan 18.
High post-transplantation cell mortality is the main limitation of various approaches that are aimed at improving regeneration of injured neural tissue by an injection of neural stem cells (NSCs) and mesenchymal stromal cells (MStroCs) in and/or around the lesion. Therefore, it is of paramount importance to identify efficient ways to increase cell transplant viability. We have previously proposed the "evolutionary stem cell paradigm," which explains the association between stem cell anaerobic/microaerophilic metabolic set-up and stem cell self-renewal and inhibition of differentiation. Applying these principles, we have identified the main critical point in the collection and preparation of these cells for experimental therapy: exposure of the cells to atmospheric O, that is, to oxygen concentrations that are several times higher than the physiologically relevant ones. In this way, the primitive anaerobic cells become either inactivated or adapted, through commitment and differentiation, to highly aerobic conditions (20%-21% O in atmospheric air). This inadvertently compromises the cells' survival once they are transplanted into normal tissue, especially in the hypoxic/anoxic/ischemic environment, which is typical of central nervous system (CNS) lesions. In addition to the findings suggesting that stem cells can shift to glycolysis and can proliferate in anoxia, recent studies also propose that stem cells may be able to proliferate in completely anaerobic or ischemic conditions by relying on anaerobic mitochondrial respiration. In this systematic review, we propose strategies to enhance the survival of NSCs and MStroCs that are implanted in hypoxic/ischemic neural tissue by harnessing their anaerobic nature and maintaining as well as enhancing their anaerobic properties via appropriate ex vivo conditioning.
移植后细胞死亡率高是各种旨在通过在损伤部位及其周围注射神经干细胞（NSCs）和间充质基质细胞（MStroCs）来改善受损神经组织再生的方法的主要限制。因此，确定提高细胞移植存活率的有效方法至关重要。我们之前提出了“进化干细胞范式”，该范式解释了干细胞厌氧/微需氧代谢模式与干细胞自我更新及分化抑制之间的关联。应用这些原理，我们确定了在实验性治疗中收集和制备这些细胞的主要关键点：使细胞暴露于大气中的氧气，即暴露于比生理相关浓度高出数倍的氧气浓度下。这样一来，原始的厌氧细胞要么失活，要么通过定向分化适应高氧环境（大气中氧气含量为20%-21%）。一旦将这些细胞移植到正常组织中，尤其是在中枢神经系统（CNS）损伤典型的缺氧/无氧/缺血环境中，这会无意中损害细胞的存活。除了有研究表明干细胞可以转向糖酵解并在缺氧条件下增殖外，最近的研究还提出干细胞可能能够依靠无氧线粒体呼吸在完全厌氧或缺血条件下增殖。在本系统综述中，我们提出了一些策略，通过利用NSCs和MStroCs的厌氧特性，并通过适当的体外预处理维持和增强其厌氧特性，来提高植入缺氧/缺血神经组织中的这些细胞的存活率。
