Clemson-MUSC Bioengineering Program, Department of Bioengineering, Clemson University, Charleston, SC 29425, USA.
Med Hypotheses. 2012 Aug;79(2):274-7. doi: 10.1016/j.mehy.2012.05.010. Epub 2012 May 31.
Consequences of central nervous system (CNS) physical injuries and neurodegenerative diseases are severe because the CNS has limited capacity to replace neurons lost through injuries or diseases. Neural stem cells (NSCs) are the most versatile and promising cell source for the regeneration of injured and diseased CNS. However, cell therapy faces many problems related to cell survival, control of cell fate and proper cell engraftment after transplantation. Cell survival is one of the most challenging technical issues as only a small percentage of implanted cells can survive after transplantation. These cells often die in the first few days after transplantation due to acute inflammation/immune response, trophic factor withdrawal, oxidative stress, excitotoxicity, hypoxia, or anoikis. To use appropriate size of cell aggregates, such as neurospheres, rather than individual cell suspension, may prevent anoikis and improve viability. Cells in aggregates or groups can form a community to provide paracrine signaling or trophic support for neighboring transplanted cells to be able to survive in the community manner. One important parameter in the neurosphere structure is the size or diameter. If the sphere size is too big, the nutrient and oxygen support for the cells in the core of the neurosphere will be limited or insufficient. If the sphere size is too small, the beneficial impact of the multicellular community may be limited. To this end, we hypothesize that the survival of transplanted NSCs may be improved with the transplantation of multicellular neurospheres as compared to the transplantation of individual cells in suspension, and there is an optimal range of the sphere size to get the highest viability for the transplanted neural cells. Another major factor is the immune response to the transplanted neural cells. Even with immunosuppressant used, host immune response can still jeopardize the viability of the transplanted cells. Mesenchymal stem cells (MSCs) have been demonstrated to possess immunosuppressive and neuroprotective properties. We further hypothesize that the viability of transplanted neural cells may be further improved in neurospheres coated with layers of MSCs on the surface of neurospheres by suppressing the host immune response at the transplantation site.
中枢神经系统（CNS）物理损伤和神经退行性疾病的后果很严重，因为 CNS 替换因损伤或疾病而丧失的神经元的能力有限。神经干细胞（NSC）是受伤和患病的 CNS 再生最具多功能和最有前途的细胞来源。然而，细胞治疗面临着许多与细胞存活、细胞命运控制和移植后适当细胞植入相关的问题。细胞存活是最具挑战性的技术问题之一，因为只有一小部分植入细胞在移植后能够存活。这些细胞在移植后的头几天经常因急性炎症/免疫反应、营养因子缺失、氧化应激、兴奋毒性、缺氧或失巢凋亡而死亡。使用适当大小的细胞聚集体，如神经球，而不是单个细胞悬浮液，可以防止失巢凋亡并提高存活率。聚集体或群体中的细胞可以形成一个社区，为相邻移植细胞提供旁分泌信号或营养支持，以便以社区方式存活。神经球结构中的一个重要参数是大小或直径。如果球体太大，球体核心细胞的营养和氧气支持将受到限制或不足。如果球体太小，多细胞社区的有益影响可能会受到限制。为此，我们假设与单个细胞悬浮液相比，移植多细胞神经球可以提高移植 NSC 的存活率，并且存在一个最佳的球体大小范围，可以使移植的神经细胞获得最高的存活率。另一个主要因素是对移植神经细胞的免疫反应。即使使用免疫抑制剂，宿主免疫反应仍可能危及移植细胞的活力。间充质干细胞（MSC）已被证明具有免疫抑制和神经保护特性。我们进一步假设，通过在神经球表面涂覆多层 MSC 来抑制移植部位的宿主免疫反应，可进一步提高涂覆有 MSC 的神经球中移植神经细胞的存活率。
