PARKINSON: STEM CELLS

Parkinson's Disease (PD) is a neurodegenerative disorder characterized by the selective deterioration of

dopaminergic neurons located in the pars compacta of the substantia nigra. This neuronal loss leads to a

significant reduction in dopamine, a neurotransmitter essential for modulating the motor circuits of the striatum.

The dopaminergic deficit compromises motor control, resulting in cardinal symptoms such as bradykinesia, muscle rigidity, resting tremor, and postural instability. As the disease progresses, cognitive impairments and behavioral alterations also emerge, significantly impacting the individual’s quality of life.

Current pharmacological therapies can provide temporary symptomatic relief but do not halt the underlying degenerative process. In this regard, research on stem cells, particularly the use of pluripotent stem cells, is gaining increasing relevance as a potential therapeutic approach aimed at counteracting the neurological damage induced by Parkinson’s.

Pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), possess the unique ability to differentiate into various cell types, including dopaminergic neurons. The latter offer a distinct advantage over the former, as they can be derived from the patient’s own somatic cells, thereby reducing the risk of immune rejection and addressing ethical concerns related to the use of embryos.

Recent phase I and II clinical trials are exploring the transplantation of these neurons (derived from human ESCs) into the brains of affected patients. The goal is to assess the safety and tolerability of the graft while simultaneously monitoring these neurons’ ability to integrate into damaged brain circuits, restore dopaminergic functionality, and sustain long-term survival and activity.

In parallel, the STEM-PD project, co-funded by the European Research Council (ERC), aims to develop personalized therapies using iPSC-based models. By enabling the generation of patient-specific neurons, these models could not only enhance treatment efficacy, but also reduce the risk of rejection-related side effects. Additionally, the possibility of creating brain organoids in vitro provides a highly sophisticated three-dimensional model, allowing for the study of Parkinson’s pathophysiology and the early development of novel pharmacological compounds.

Another innovative aspect is the use of advanced bioengineering techniques, such as biomaterial scaffolds, which serve as structural support for transplanted elements, facilitating their preservation and proper integration within the existing neuroanatomical framework.

Moreover, stem cells may exert neuroprotective effects by modulating inflammatory processes, which play a key role in disease progression. Beyond that, emerging evidence suggests that their paracrine effects can lead to the secretion of neurotrophic factors beneficial for preserving neural plasticity and mitigating damage caused by hyperactive microglia.

- 𝐷𝑟. 𝐿𝑒𝑣𝑖𝑛𝑒 𝑆𝑝𝑒𝑛𝑐𝑒𝑟

𝑆𝑝𝑒𝑐𝑖𝑎𝑙𝑖𝑠𝑡 𝑖𝑛 𝑃𝑠𝑦𝑐ℎ𝑜-𝐺𝑒𝑛𝑒𝑡𝑖𝑐𝑠