دانلود رایگان مقاله انگلیسی نقش عملکرد سلول های بنیادی مزانشیمی در درمان بیماری های مزمن نروزی - وایلی 2017

Abstract

Mesenchymal stem cells (MSCs) can differentiate into not only cells of mesodermal lineages, but also into endodermal and ectodermal derived elements, including neurons and glial cells. For this reason, MSCs have been extensively investigated to develop cell-based therapeutic strategies, especially in pathologies whose pharmacological treatments give poor results, if any. As in the case of irreversible neurological disorders characterized by progressive neuronal death, in which behavioral and cognitive functions of patients inexorably decline as the disease progresses. In this review, we focus on the possible functional role exerted by MSCs in the treatment of some disabling neurodegenerative disorders such as Alzheimer's Disease, Amyotrophic Lateral Sclerosis, Huntington's Disease and Parkinson's Disease. Investigations have been mainly performed in vitro and in animal models by using MSCs generally originated from umbilical cord, bone marrow or adipose tissue. Positive results obtained have prompted several clinical trials, the number of which is progressively increasing worldwide. To date, many of them have been primarily addressed to verify the safety of the procedures but some improvements have already been reported, fortunately. Although the exact mechanisms of MSC-induced beneficial activities are not entirely defined, they include neurogenesis and angiogenesis stimulation, antiapoptotic, immunomodulatory and antiinflammatory actions. Most effects would be exerted through their paracrine expression of neurotrophic factors and cytokines, mainly delivered at damaged regions, given the innate propensity of MSCs to home to injured sites. Hopefully, in the near future more efficacious cell-replacement therapies will be developed to substantially restore disease-disrupted brain circuitry. This article is protected by copyright.

Conclusions

Data from the studies above described show that the use of MSCs may induce appreciable amelioration in neurodegenerative diseases, where only poor results can be achieved by pharmacological approaches or other therapeutic strategies. Beneficial MSC-induced effects primarily rely on their particular tendency to home to injured areas, in particular to hypoxic, apoptotic or inflamed areas (Fig.1). Notably, their ability to pass the BBB has permitted different administration routes (Kerkis et al., 2015). In fact, MSC engrafting at the injured nervous tissue has been reported not only upon intracerebral injection, but also after intracerebroventricular, intracarotid, intravenous, or even intranasal administration.

However, it should be pointed out that, although less invasive, systemic administrations have some limitations. After intravenous injections, many cells are trapped in the lungs and fail to reach target tissues. Intra-arterial delivery implies more invasive procedures and may lead to microthrombi formation, thus compromising tissue microcirculation. The wide dispersion of cells in the blood stream would require a strong homing ability, which may be affected by the loss of expression of homing molecules during in vitro expansion. In this regard, different strategies have been developed. For example, by expanding MSCs under hypoxic conditions, by adding various chemicals or cytokines to the culture medium or by genetic engineering to overexpress homing molecules. These issues have been extensively addressed in a recent review by De Becker and Van Riet (2016).