Parkinson’s disease (PD) is a neurodegenerative disorder affecting millions worldwide, causing debilitating symptoms such as tremors, rigidity, and difficulty walking. Existing treatments primarily manage symptoms without addressing the underlying causes, highlighting the need for more effective therapeutic approaches. Mesenchymal stem cell (MSC) therapy has emerged as a promising option, demonstrating potential neuroprotective, anti-inflammatory, and regenerative benefits.
As part of this review, Tambe et al. examine preclinical and clinical evidence on MSCs and their derivatives, including secretomes and exosomes, in PD management. The authors also analyze challenges and limitations of each approach, including delivery methods, timing of administration, and long-term safety considerations.
The Growing Challenge of Parkinson’s Disease
PD, along with other age-related diseases like Alzheimer’s and stroke, is becoming more prevalent due to increased life expectancy. The disease affects 2–3% of individuals over 65, and by 2040, the number of people living with PD is expected to double. In 2019, PD caused the loss of 5.8 million disability-adjusted life years (DALYs), a significant rise from 2000.
PD symptoms include postural instability, muscle hypertonia, bradykinesia, resting tremor, and cognitive and language abnormalities, all of which negatively impact the quality of life. PD is diagnosed based on motor symptoms, but non-motor symptoms also contribute to disability.
Parkinson’s disease primarily results from the accumulation of α-synuclein and a depletion of dopamine due to neuronal loss in the substantia nigra. It also involves disruptions in multiple pathways, including α-synuclein proteostasis, mitochondrial dysfunction, oxidative stress, and neuroinflammation.
Current Treatments for Parkinson’s Disease
While there is no cure for PD, current symptomatic treatments include levodopa, dopamine agonists, MAO-B inhibitors, COMT inhibitors, deep brain stimulation, and lesion surgery. However, these therapies are limited and do not address the underlying causes of the disease.
Newer interventions like stem cell therapy, neurotrophic factors, and gene therapy aim to address the root causes and potentially slow or stop disease progression.
Cell-based Therapies for Parkinson’s Disease
Cell-based therapies are gaining attention as potential treatments for PD due to their ability to slow disease progression and replace lost dopamine production. Several cell sources are being researched for their therapeutic potential, each with specific advantages and disadvantages.
Mesenchymal stem cells (MSCs) are particularly promising due to their unique properties, including self-renewal and multi-potent differentiation potential. MSCs can differentiate into various cell types, including neuronal-like cells, and exhibit therapeutic effects through both cellular differentiation and the paracrine action of secreted growth factors.
Properties of Mesenchymal Stem Cells (MSCs)
MSCs are plastic-adherent cells capable of self-renewal and differentiation into various lineages, including neurons, adipocytes, osteoblasts, chondrocytes, and endothelial cells. This versatility makes MSCs an attractive option for treating PD.
MSCs also have the potential to exert therapeutic effects through the secretion of factors that promote cell survival, tissue regeneration, and anti-inflammatory actions. In addition to their ability to differentiate into mesodermal lineages, MSCs can produce secretomes and exosomes, which are small vesicles containing proteins, RNA, and other molecules that have demonstrated the ability to influence surrounding cells.
Therapeutic Success of MSCs in PD Management
Preclinical studies on MSCs and their derivatives, including secretomes and exosomes, have shown promising results in PD animal models. MSCs may promote the survival of dopamine-producing neurons and protect against neurodegeneration. Their secretomes, which contain bioactive molecules, can modulate inflammation and stimulate tissue repair. Exosomes, which are extracellular vesicles derived from MSCs, have been shown to improve neuronal function and survival in PD models. These findings suggest that MSC-based therapies could offer a novel approach to managing PD, potentially slowing disease progression and improving motor and cognitive symptoms.
Alternative Delivery Methods for MSC Therapy
One of the significant challenges in MSC therapy for PD is the delivery of these cells to the brain, particularly through the blood-brain barrier (BBB), which restricts the entry of most drugs.
Traditional delivery methods, such as intravenous, intracerebral, and intramuscular routes, have limitations in terms of efficacy and invasiveness.
Recent research has explored intranasal delivery of MSCs and their derivatives as a promising alternative. Intranasal administration could allow MSCs and their secretomes to bypass the BBB, delivering therapeutic agents directly to the central nervous system with minimal invasiveness.
The Future of MSC Therapy for Parkinson’s Disease
MSC-released exosomes and extracellular vesicles are gaining attention as potential treatments for PD due to their improved ability to cross the BBB and target specific cells. These vesicles can transport proteins, growth factors, microRNAs, and other bioactive molecules to recipient cells, potentially enhancing the therapeutic effects of MSCs.
Intranasal delivery of MSCs and their exosomes is an exciting area of research, offering a less invasive method for delivering therapy directly to the brain. This approach could lead to improved outcomes in PD management, especially if combined with other therapies that address the underlying causes of the disease.
Tambe et al. conclude that MSC therapy and its derivatives, such as secretomes and exosomes, hold significant promise for the treatment of Parkinson’s disease. However, challenges such as MSC heterogeneity, delivery methods, and long-term safety must be addressed before MSC-based therapies can become a mainstream treatment for PD.
Source: Tambe P, Undale V, Sanap A, Bhonde R, Mante N. The prospective role of mesenchymal stem cells in Parkinson’s disease. Parkinsonism Relat Disord. 2024 Oct;127:107087. doi: 10.1016/j.parkreldis.2024.107087. Epub 2024 Aug 10. PMID: 39142905.
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