Stem Cell Therapies for Progressive Multiple Sclerosis

Stem Cell Therapies for Progressive Multiple Sclerosis

Multiple sclerosis (MS) is a long-term inflammatory disease that affects the central nervous system (CNS) of an estimated 3 million people worldwide. Characterized by the loss of the protective covering (myelin) of nerve fibers and degeneration of the nerve fibers themselves, MS damage disrupts communication between the brain and the rest of the body. Most MS patients start with a form known as relapsing-remitting MS (RRMS), where symptoms flare up at intervals and then partially or fully improve. Typical symptoms during these flare-ups include lack of muscle control, fatigue, and sensory impairments.

As the disease progresses, many individuals transition from RRMS to a progressive form of MS. Progressive MS is marked by a steady decline in function and an accumulation of disabilities, rather than periodic attacks. Unfortunately, the treatment options for progressive MS (PMS) are limited and often ineffective. The few available medications can help with active forms of PMS but are generally poor at slowing down the disease’s progression or promoting repair of damaged tissues.

The Promise of Stem Cell Therapy

Stem cell therapy has emerged as a promising approach to addressing the needs of patients with PMS. Stem cells have the unique ability to develop into various types of cells and offer several potential benefits, including providing support to nerve cells, modulating the immune system, and even replacing damaged cells. These characteristics make stem cells an attractive option for treating the complex pathology of PMS.

Current State of Stem Cell Therapy Research

In this review, Smith et al. explore the current state of preclinical and clinical evidence supporting the use of stem cells in treating PMS and discuss prospective hurdles impeding their translation into revolutionary regenerative medicines.

According to the authors, preclinical studies suggest that stem cells might help by reducing inflammation and protecting nerve cells in the CNS. However, translating these findings into effective treatments for humans remains a challenge.

Existing disease-modifying therapies (DMTs) have improved the treatment of RRMS by targeting the immune system to prevent the attacks that cause demyelination and nerve damage. These therapies work well for RRMS because they address the inflammatory processes that drive the disease. Unfortunately, as patients transition to the progressive phase of MS, conventional DMTs become less effective. PMS is characterized by a different set of pathological processes, including persistent inflammation behind a closed blood-brain barrier and activation of microglia (the brain’s immune cells) rather than T and B cells.

Stem Cell Therapy’s Potential Benefits

According to Smith et al. stem cell therapy offers potential benefits in several ways, including

  • Neuroprotection: Stem cells can potentially protect nerve cells from damage and death, which is crucial in progressive forms of MS.
  • Immunomodulation: Stem cells might help modulate the immune system, reducing harmful inflammation that contributes to disease progression.
  • Cell Replacement: Stem cells have the potential to replace damaged cells and promote the repair of damaged tissues.

While these potential benefits are compelling, the authors have found that the effectiveness of stem cell therapy in PMS is still largely unproven in clinical settings. The majority of current stem cell research focuses on the relapsing forms of MS or other diseases, with fewer studies dedicated specifically to PMS.

Current Status and Future Prospects

Stem cell therapy has demonstrated safety and feasibility across different types of cells and administration methods. The most promising results so far have been in studies involving neural stem cells (NSCs), which have shown potential in preclinical models for reducing chronic neuroinflammation. However, substantial clinical research is needed to validate these findings and determine the practical benefits of stem cell therapy for PMS.

The authors conclude that while stem cell therapy holds considerable promise for treating progressive multiple sclerosis, more research is needed. Future studies should focus on large, well-designed clinical trials to assess the benefits and risks of stem cell treatments. If proven effective, Smith et al. believe that stem cell therapy could become a revolutionary treatment for PMS and offer hope to millions of patients affected by this debilitating condition.

Source: Smith JA, Nicaise AM, Ionescu RB, Hamel R, Peruzzotti-Jametti L, Pluchino S. Stem Cell Therapies for Progressive Multiple Sclerosis. Front Cell Dev Biol. 2021;9:696434. Published 2021 Jul 9. doi:10.3389/fcell.2021.696434

Exploring Cell Therapy for Neuropathic Pain

Exploring Cell Therapy for Neuropathic Pain

Neuropathic pain (NP) occurs when the nerves located either inside or outside of the brain and spinal cord are damaged by a lesion or a condition. To date, pharmacological and surgical treatments to address NP have focused on providing symptomatic relief without treating the underlying cause of the condition. These treatment approaches have not been overwhelmingly successful with over 50% of NP patients attaining adequate pain relief.

Recently, an increasing amount of pre-clinical and clinical research has demonstrated cell transplantation-based therapy for NP to be a promising treatment alternative.  

In this review, Yin et al. summarize the use of cell grafts for the treatment of NP, synthesize the latest advances and adverse effects, and discuss possible mechanisms to further the development of cell transplant-based therapies for NP. 

Neural stem cells (NSCs) demonstrate the ability to divide, self-renew, and differentiate into neurons, astrocytes, and oligodendrocytes; they are also present in a wide array of tissues throughout the body. Considering they are capable of differentiating into neurons and glial, NSCs are considered an ideal candidate cell for replacing damaged nerve cells and delivering trophic factors to the site of lesions contributing to NP. Additional studies have demonstrated NSCs ability to regenerate nerves, offer neuroprotective effects, and secrete a number of factors that enhance the survival of motor and sensory neurons. NSCs transplantation coils also ease NP caused by peripheral nerve injury, a potential benefit that has been observed in animal models.

Olfactory ensheathing cells (OECs) are glial cells that surround and enclose the olfactory nerve bundle and possess the unique ability to transgress the peripheral nervous system (PNS) and central nervous system (CNS). Considering OECs have been shown to have neuro-regenerative functions, they are also considered to be a good choice for treating nerve injury and NP. Studies using animal models have confirmed that OECs transplantation could promote motor recovery and mitigate pain. Although OECs have good prospects of being used for treating NP, the authors call for additional research with longer observation time to verify their long-term effects and safety.

Mesenchymal stem cells (MSCs) can be obtained from a wide variety of sources and can be induced to differentiate into endoderm, mesoderm, and ectoderm cell lines. MSCs are often used for the treatment of diseases involving neuroinflammatory components and have been shown in animal studies to potentially alleviate NP symptoms. 

Other cell therapies currently being evaluated for use as a treatment for NP include bone marrow mononuclear cells, GABAergic cells, and genetically modified cells. 

The authors conclude that, despite the small number of clinical studies and the lack of systematic evidence, cell therapy as a treatment alternative for NP should be further explored. Specifically, further research should examine the optimal transplantation route, transplantation timing, number of transplanted cells, and transplantation survival rate.


Source:  “Cell therapy for neuropathic pain – Frontiers.” 27 Feb. 2023, https://www.frontiersin.org/articles/10.3389/fnmol.2023.1119223.

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