Introduction: Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder, following Alzheimer's disease. It can result from genetic mutations and lead to a range of motor and non-motor impairments. The main current treatment is the use of drugs that enhance dopamine in the brain, such as levodopa, by dopamine agonists or inhibition of dopamine degradation. However, in a futuristic approach, cell-based therapies, including regenerating and transplanting dopaminergic neurons into the striatum and other brain regions, hold great promise. These cell therapies draw from various types of stem cells, containing embryonic stem cells (ESCs), hematopoietic stem cells (HSCs), neural stem cells (NSCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs)
Methods: In this article, we review research related to ESCs, MSCs, and iPSCs based on an extensive search of the PubMed database, along with additional references from the NCBI and OSCI databases. Our focus is on recent research published within the last five years, with a limited number of 2023 review articles serving as references for an overview
Results: Each group promises a bright future for Parkinson's treatment; ESCs are important in preclinical and clinical studies. In examining this group, their unique genes are important in the overexpression of several transcription factors related to dopaminergic mesencephalic phenotype and the improvement of motor symptoms of PD; also, in a dedicated transplant from cryopreserved clinical-grade ESCs, named MSK-DA01, the presence of human Tyrosine hydroxylase cells at the transplant site is confirmed.
In a newer way, the use of MSCs has fewer restrictions and is more effective; MSCs can be obtained from both allogeneic and autologous sources. The efficiency of this group of cells is broad, but perhaps the most interesting way of using these cells is the use of extracellular vesicles.
These extracellular vesicles or exosomes are the paracrine functional components of MSCs and, as nanoscopic particles, they carry molecules like miRNA. MiRNAs are proven markers of the possible diagnosis and treatment; they also say the gene expression pattern in the stage of the formation of this nucleic acid is effective in the occurrence of the disease.
These exosomes help to maintain the active state of transcription in brain vascular endothelial cells (HBMECs) and have a positive effect on the angiogenesis process; the contents of these exosomes affect angiogenesis by increasing the expression of ICAM1. Angiogenesis is important in the treatment of diseases such as PD because it helps the diffusion of substances along newly formed tissues.
On the other hand, advances in the use of iPSCs have a latent potential to serve as a type of cell therapy. All iPSC lines can be differentiated into dopaminergic neurons, providing valuable tools for studying the pathogenesis of PD.
It states, that iPSC is a cell therapy product that can be transplanted without the risk of immune rejection and eliminating the need for immunosuppression and related side effects. Therapeutic methods like autologous transplant, allogeneic transplant without matching human leukocyte antigen, and allogeneic transplant with matching are utilized to mitigate the risk of immune rejection.
However, a major drawback of autologous grafts is that the transplanted cells may still carry genetic mutations or risk factors contributing to PD. For example, the SNCA gene is responsible for α-synucleinopathies and is a common cause of neurodegeneration. The most prevalent alpha-synucleinopathy arises from the abnormal accumulation of α-syn. Mutations in the PARK2 and GBA genes represent other detrimental mutations.
Conclusion: In conclusion, the purpose of this article is to introduce and compare the performance of three groups: embryonic, mesenchymal, and induced pluripotent stem cells, as cell-based treatments for Parkinson's disease. Most studies conducted reveal similar results in both in vitro and in vivo conditions, with the occurrence of tumorigenesis and teratoma formation being rare.
Nonetheless, challenges persist, including identifying suitable transplantation sources, immunogenicity post-transplantation, ethical concerns, and dealing with the limitations of treating advanced diseases. A comprehensive comparison can pave the way for effective treatment. It is noteworthy that mesenchymal stem cells currently represent one of the most debated treatment methods, but is this approach the most efficacious one?