Mesenchymal Stromal Cell Therapies for Neurodegenerative Diseases

Abstract

Mesenchymal stromal cells are multipotent cells that are being used to treat a variety of medical conditions. Over the past decade, there has been considerable excitement about using MSCs to treat neurodegenerative diseases, which are diseases that are typically fatal and without other robust therapies. In this review, we discuss the proposed MSC mechanisms of action in neurodegenerative diseases, which include growth factor secretion, exosome secretion, and attenuation of neuroinflammation. We then provide a summary of preclinical and early clinical work on MSC therapies in amyotrophic lateral sclerosis, multiple system atrophy, Parkinson disease, and Alzheimer disease. Continued rigorous and controlled studies of MSC therapies will be critical in order to establish efficacy and protect patients from possible untoward effects. ª 2019 Mayo Foundation for Medical Education and Research n Mayo Clin Proc. 2019;94(5):892-905

RETRACTED: Resveratrol Preincubation Enhances the Therapeutic Efficacy of hUC-MSCs by Improving Cell Migration and Modulating Neuroinflammation Mediated by MAPK Signaling in a Mouse Model of Alzheimer’s Disease

“…Normally, the blood-brain barrier prevents the penetration of MSCs, but it is believed that the integrity of the blood-brain barrier is impaired in response to injury or under neurodegenerative conditions, thereby facilitating the infiltration of MSCs into the brain. Accumulating evidence has shown that intravenously transplanted MSCs can penetrate the blood-brain barrier, dampen neural apoptosis, enhance neurogenesis, and improve learning and memory in AD mice (Mukai et al, 2018;Staff et al, 2019). MSCs have emerged as promising agents in combating AD.…”

Translating intracarotid artery transplantation of bone marrow-derived NCS-01 cells for ischemic stroke: Behavioral and histological readouts and mechanistic insights into stem cell therapy

“…8,9 Adult bone marrow-derived stem cells, such as endothelial progenitor cells, hematopoietic, and mesenchymal stem cells (MSCs), have expedited the translation of lab-to-clinic stem cell therapy due to their logistical ease in isolation and amplification, and being relatively free from ethical concerns. 10,11 MSCs have been explored as transplantable donor cells for many experimental models of neurological diseases, 12,13 such as Parkinson's disease, [14][15][16] amyotrophic lateral sclerosis, [17][18][19] Alzheimer's disease, 20,21 and stroke. [22][23][24][25][26][27][28] Cell replacement was initially implicated in MSCs' therapeutic effects, yet with only modest graft survival despite robust functional outcomes, 29 the currently accepted mechanism of action involves bystander repair processes primarily via stem cell-secreted therapeutic factors.…”

Extracellular Vesicles as Nanotherapeutics for Parkinson’s Disease

“…As already mentioned for NSCs, the benefits of MSCs seem to be mediated also via their secretome, including the EV component, as demonstrated by several studies [217][218][219]. Despite MSCs transplantation ameliorated PD symptoms, the trophic effects were often only transient [220,221]. Moreover, in some cases, the systemic injection of these cells showed severe side effects, such as pulmonary thrombosis [222][223][224][225], whereas the alternative intracranial transplantation is a very invasive procedure [215].…”