A potential treatment for Amyotrophic Lateral Sclerosis (ALS), a neurological disease that damages motor neurones and causes progressive muscular weakness, paralysis, and eventually death, is being investigated using umbilical cord-derived mesenchymal stem cells (UC-MSCs). Presently, there is no known cure for ALS, and existing therapies only slightly impede the disease’s advancement. Because of their special qualities, UC-MSCs are a good option for ALS treatment because of their capacity to regulate immune responses, release neurotrophic substances, and shield neurones.
UC-MSCs’ Mode of Action in ALS
- Neuroprotection:
- The gradual loss of motor neurones is one of the primary problems associated with ALS. Through the release of neurotrophic factors, which promote neurone survival and function, UC-MSCs aid in the protection of motor neurones. Among these are:
- Neurotrophic factor derived from the brain (BDNF): Enhances motor neurone function and survival.
- Glial cell line-derived neurotrophic factor (GDNF): Promotes motor neurone survival and guards against programmed cell death, or apoptosis.
- Nerve Growth Factor (NGF): Assists in the development and upkeep of neurones, hence lowering the rate of neuronal death in ALS.
- Immune modulation:
- In ALS, there is evidence of persistent inflammation and immunological dysregulation in the central nervous system. UC-MSCs can modify the immune response and minimise this detrimental inflammation:
- UC-MSCs emit anti-inflammatory cytokines such IL-10 and TGF-β, suppressing the pro-inflammatory milieu in the CNS.
- UC-MSCs reduce levels of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, which can cause neuronal injury in ALS.
- Modulation of microglia and astrocytes: UC-MSCs can change the activation state of microglia and astrocytes, the CNS’s immune cells, from pro-inflammatory (which exacerbates neurodegeneration) to anti-inflammatory (which protects neurones).
- Reduced Oxidative Stress:
- Oxidative stress is a major role in the course of ALS, causing further damage to motor neurones. UC-MSCs can reduce oxidative stress by secreting antioxidants and promoting the repair of oxidative damage.
- UC-MSCs produce substances that neutralise reactive oxygen species (ROS), which cause oxidative damage in cells. This protective impact can reduce the rate of motor neurone degeneration.
- Enhanced Mitochondrial Function:
- In ALS, motor neurones frequently show mitochondrial dysfunction, which reduces energy generation and increases oxidative stress. UC-MSCs produce chemicals that increase mitochondrial function, boosting energy generation and lowering cellular stress in motor neurones.
- Promoting Motor Neurone Survival:
- UC-MSCs may directly support the survival of motor neurones through:
- Inducing axonal growth: UC-MSCs enhance axonal regeneration by secreting growth factors such as VEGF and BDNF, which can assist preserve functional connections between motor neurones and muscle cells.
- Reduced excitotoxicity: Excitotoxicity, or an excess of the neurotransmitter glutamate, contributes to neuronal death in ALS. UC-MSCs have been demonstrated to regulate glutamate levels, thereby shielding motor neurones from hazardous overactivation.
- Replace Damaged Cells (Potential Differentiation):
- While the primary mechanism of UC-MSCs in ALS is likely paracrine signalling (the release of helpful chemicals), other studies indicate that UC-MSCs may have the ability to develop into neuron-like cells or stimulate the formation of new motor neurones. This is currently under development, but it may provide a more direct method to replenishing missing neurones in ALS
UC-MSCs can be administered to ALS patients using various approaches based on therapy aims.
- Intravenous (IV) infusion of UC-MSCs allows them to pass the blood-brain barrier and target inflammation and damage areas. While this strategy is less intrusive, research is being conducted to establish the efficacy of IV delivery in directly targeting the CNS.
- Intrathecal (IT) Injection: UC-MSCs are injected directly into the CSF, which surrounds the brain and spinal cord. IT delivery enables cells to reach the CNS more efficiently, enhancing their ability to impact motor neurones and give neuroprotective advantages. This is the most prevalent method of distribution in clinical trials.
- Intraparenchymal Injection:
Experimental treatments involve injecting UC-MSCs directly into areas of the spinal cord with motor neurone degeneration. This precise administration guarantees that the cells are close to the injured neurones, maximising their potential for regeneration.
Overview of UC-MSCs in ALS Treatment:
- Neuroprotection: UC-MSCs secrete neurotrophic factors such as BDNF and GDNF, which protect motor neurones from degeneration.
- Immunomodulation: UC-MSCs diminish inflammation in the CNS by regulating immune cells and inhibiting pro-inflammatory cytokines.
- Oxidative stress reduction: UC-MSCs help to minimise oxidative damage to motor neurones, which is a major role in ALS
- Mitochondrial support: UC-MSCs enhance mitochondrial function, hence preserving motor neurone energy levels and function.
- Excitotoxicity reduction: UC-MSCs regulate glutamate levels, which reduces the negative effects of excitotoxicity on motor neurones.