中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (3): 478-484.doi: 10.4103/1673-5374.350193

• 综述:退行性病与再生 • 上一篇    下一篇

治疗帕金森病的基于细胞的联合治疗策略:专注于间充质基质细胞

  

  • 出版日期:2023-03-15 发布日期:2022-08-25
  • 基金资助:

Combined cell-based therapy strategies for the treatment of Parkinson’s disease: focus on mesenchymal stromal cells

Jannette Rodríguez-Pallares1, 2, *, María García-Garrote1, 2, Juan A. Parga1, 2, José Luis Labandeira-García1, 2, *   

  1. 1Laboratory 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, Spain; 2Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
  • Online:2023-03-15 Published:2022-08-25
  • Contact: José Luis Labandeira-García, MD, PhD, joseluis.labandeira@usc.es; Jannette Rodríguez-Pallares, PhD, jannette.rodriguez@usc.es.
  • Supported by:
    This work was supported by grants from Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (ED431G/05, ED431C 2018/10), European Regional Development Fund (FEDER), Instituto de Salud Carlos III (RD16/011/0016; RD21/0017/0031), Secretaría de Estado de Investigación, Desarrollo e Innovación (Grant/Award, number RTI2018‐098830‐B‐I00) (to JLLG).

摘要:

https://orcid.org/0000-0001-6865-2433 (Jannette Rodríguez-Pallares); 

https://orcid.org/0000-0001-7155-7234 (María García-Garrote); 

https://orcid.org/0000-0003-2072-5642 (Juan A. Parga); 

https://orcid.org/0000-0002-8243-9791 (José Luis Labandeira-García)

Abstract: 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. 

Key words: brain repair, cell replacement, co-grafts, dopaminergic neurons, fetal ventral mesencephalic tissue, mesenchymal stem cells, neural grafting, neural transplantation, neuroblasts, neurotrophic factors