Rodríguez-Pallares Jannette, García-Garrote María, Parga Juan A, Labandeira-García José Luis
Laboratory of Cellular and Molecular Neurobiology of Parkinson's Disease, Research Center for Molecular Medicine and Chronic Diseases (CiMUS), IDIS, Department of Morphological Sciences, University of Santiago de Compostela, Santiago de Compostela; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
Neural Regen Res. 2023 Mar;18(3):478-484. doi: 10.4103/1673-5374.350193.
Parkinson's disease is a neurodegenerative condition characterized by motor impairments caused by the selective loss of dopaminergic neurons in the substantia nigra. Levodopa is an effective and well-tolerated dopamine replacement agent. However, levodopa provides only symptomatic improvements, without affecting the underlying pathology, and is associated with side effects after long-term use. Cell-based replacement is a promising strategy that offers the possibility to replace lost neurons in Parkinson's disease treatment. Clinical studies of transplantation of human fetal ventral mesencephalic tissue have provided evidence that the grafted dopaminergic neurons can reinnervate the striatum, release dopamine, integrate into the host neural circuits, and improve motor functions. One of the limiting factors for cell therapy in Parkinson's disease is the low survival rate of grafted dopaminergic cells. Different factors could cause cell death of dopaminergic neurons after grafting such as mechanical trauma, growth factor deprivation, hypoxia, and neuroinflammation. Neurotrophic factors play an essential role in the survival of grafted cells. However, direct, timely, and controllable delivery of neurotrophic factors into the brain faces important limitations. Different types of cells secrete neurotrophic factors constitutively and co-transplantation of these cells with dopaminergic neurons represents a feasible strategy to increase neuronal survival. In this review, we provide a general overview of the pioneering studies on cell transplantation developed in patients and animal models of Parkinson's disease, with a focus on neurotrophic factor-secreting cells, with a particular interest in mesenchymal stromal cells; that co-implanted with dopaminergic neurons would serve as a strategy to increase cell survival and improve graft outcomes.
帕金森病是一种神经退行性疾病，其特征是黑质中多巴胺能神经元选择性丧失导致运动障碍。左旋多巴是一种有效且耐受性良好的多巴胺替代药物。然而，左旋多巴仅能改善症状，不影响潜在病理过程，且长期使用会产生副作用。基于细胞的替代疗法是一种有前景的策略，为帕金森病治疗中替代丢失的神经元提供了可能性。人胎儿腹侧中脑组织移植的临床研究已证明，移植的多巴胺能神经元可重新支配纹状体、释放多巴胺、融入宿主神经回路并改善运动功能。帕金森病细胞治疗的限制因素之一是移植的多巴胺能细胞存活率低。移植后，不同因素可能导致多巴胺能神经元细胞死亡，如机械创伤、生长因子缺乏、缺氧和神经炎症。神经营养因子在移植细胞的存活中起重要作用。然而，将神经营养因子直接、及时且可控地递送至大脑面临重大限制。不同类型的细胞可组成性分泌神经营养因子，将这些细胞与多巴胺能神经元共移植是提高神经元存活率的可行策略。在本综述中，我们概述了在帕金森病患者和动物模型中开展的细胞移植开创性研究，重点关注分泌神经营养因子的细胞，尤其关注间充质基质细胞；与多巴胺能神经元共植入将作为提高细胞存活率和改善移植效果的一种策略。
