Challenges and translational considerations of mesenchymal stem/stromal cell therapy for Parkinson’s disease

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the presence of Lewy bodies, which gives rise to motor and non-motor symptoms. Unfortunately, current therapeutic strategies for PD merely treat the symptoms of the disease, only temporarily improve the patients’ quality of life, and are not sufficient for completely alleviating the symptoms. Therefore, cell-based therapies have emerged as a novel promising therapeutic approach in PD treatment. Mesenchymal stem/stromal cells (MSCs) have arisen as a leading contender for cell sources due to their regenerative and immunomodulatory capabilities, limited ethical concerns, and low risk of tumor formation. Although several studies have shown that MSCs have the potential to mitigate the neurodegenerative pathology of PD, variabilities in preclinical and clinical trials have resulted in inconsistent therapeutic outcomes. In this review, we strive to highlight the sources of variability in studies using MSCs in PD therapy, including MSC sources, the use of autologous or allogenic MSCs, dose, delivery methods, patient factors, and measures of clinical outcome. Available evidence indicates that while the use of MSCs in PD has largely been promising, conditions need to be standardized so that studies can be effectively compared with one another and experimental designs can be improved upon, such that this body of science can continue to move forward.

Therapeutic Properties of Mesenchymal Stromal/Stem Cells: The Need of Cell Priming for Cell-Free Therapies in Regenerative Medicine

“…Over the past decade the therapeutic action of MSCs has been investigated in several clinical trials for the treatment of many disorders including cardiovascular, neurodegenerative, immune, lung, liver, kidney and orthopedics diseases ( ). In these cases, MSCs have been shown to have moderate or poor efficacy, and the results from different clinical trials are controversial [ 25 , 26 , 27 , 28 , 29 ], indicating an urgent need to optimize the therapeutic use of MSCs or to enhance MSC potency. This inconsistent evidence is potentially related both to intrinsic differences in the use of cell-based products and to the lack of standardized methods for MSC production that affects their potency.…”

Pulsed electromagnetic fields synergize with graphene to enhance dental pulp stem cell-derived neurogenesis by selectively targeting TRPC1 channels

“…Brief PEMF exposure activates TRPC1-mediated calcium entry, which stimulates mitochondrial respiration and consequent ROS production (Yap et al, 2019). PEMF exposure has been associated with ROS and superoxide production in a variety of cell types including neurons, ultimately enhancing antioxidant defenses as well as stimulating proliferation and differentiation (Ehnert et al, 2017;Falone et al, 2016;Yap et al, 2019). ROS and superoxide, although potentially damaging at high levels, at moderate levels prime mitochondrial adaptations that promote neurogenic differentiation and survival (Valero et al, 2012), through a process known as mitohormesis (Ristow and Schmeisser, 2014).…”

Interaction Between Mesenchymal Stem Cells and Retinal Degenerative Microenvironment

“…The common sources of MSCs for clinical trials of retinal degeneration therapy are bone marrow (BM) stem cells (Cotrim et al, 2017 ; Park et al, 2017 ), adipose-derived MSCs (ASC) (Oner et al, 2016 , 2018 ) and umbilical cord-derived MSCs (such as UC-MSC or palucorcel) (Heier et al, 2020 ). They differ in the ease and efficiency of harvesting, proliferative ability and senescence, and paracrine activities, which greatly affect their therapeutic potency (Fričová et al, 2020 ). For example, BM aspirate is difficult to harvest and contains only 0.001–0.01% MSCs in the overall cell population; an intensive culturing process to expand the MSCs is required for clinical use.…”

“…UC-MSCs can secrete more angiogenic, neuroprotective factors, which make them an attractive option in RDD therapy. The potential concern for UC-MSC transplantation is that, as a type of non-neuronal or non-terminally differentiated cell, they may retain a capacity for continued proliferation inside the eye after transplantation (Fričová et al, 2020 ; Singh et al, 2020 ).…”