Long-Term Post COVID-19 Afflictions: The Potential of Mesenchymal Stem Cells

The aftermath of COVID-19 continues to unfold, and as healthcare organizations worldwide grapple with the virus's lingering impact, an alarming trend emerges—long-COVID-19 or post-COVID syndrome. This blog delves into the persistent neurological afflictions that survivors face long after the virus subsides. Our focus turns to the potential therapeutic role of Mesenchymal Stem Cells (MSCs) in alleviating these enduring post-COVID neurological challenges.

Unraveling Post-COVID Syndrome

Beyond the acute infection period, many individuals experience prolonged discomforts characterized by diverse symptoms persisting for more than 12 weeks—a phenomenon termed post-COVID syndrome. Among the myriad of lingering issues, neurological afflictions stand out prominently. The elevated production of proinflammatory cytokines, known as the "cytokine storm," is identified as a major contributor to these conditions.

Post-COVID neurological afflictions encompass a spectrum of issues, including acute cerebrovascular diseases, impaired cognition, memory loss, and mental health disorders. Unfortunately, effective clinical tools to address these symptoms remain limited, necessitating innovative approaches for comprehensive treatment.

Therapeutic Properties of MSCs in Neurological Disorders

As we navigate the intricate realm of post-COVID neurological afflictions, Mesenchymal Stem Cells (MSCs) emerge as a beacon of hope. Their therapeutic properties, particularly in the context of neurological disorders, present a promising avenue for mitigating the enduring effects of the virus.

Immunomodulation

MSCs showcase remarkable abilities to modulate cytokine production, especially crucial in autoimmune diseases and prominently following the COVID-19 outbreak. Extensive studies, both in vitro and in vivo, have highlighted MSC therapy's immunomodulatory effects through intricate cell-to-cell communication and paracrine activities.

• Macrophage Polarization: MSCs influence regulatory T-cells (Treg) and monocytes, shifting macrophage polarization towards the anti-inflammatory M2 type in proinflammatory environments. Soluble signaling molecules like PGE2, IDO, IL6, and HGF play pivotal roles in this immunomodulatory dance.
• Treg Cell Proliferation: MSCs not only promote the proliferation and inhibitory capabilities of Treg cells but also inhibit the activation of T helper cells, specifically Th1 and Th17. This orchestrated regulation, including the production of IL-2 and nitric oxide, contributes to the suppression of cytotoxic T-cells, reducing cell death.

Balancing the Immune Response in Post-COVID Syndrome

In post-COVID-19 syndrome, where inflammatory cytokines run rampant, MSCs spring into action in vivo, inducing immunosuppressive activities. The production of immunosuppressive molecules, including IDO and nitric oxide, orchestrates a downregulation of proinflammatory cytokines such as IL-1β, TNF-α, IFN-ƴ, while simultaneously upregulating anti-inflammatory mediators like IL-10 and bFGF. This delicate balance aids in preventing cellular damage and organ harm.

Neuroprotective Actions of MSCs: Unveiling the Intricacies

Beyond their immunomodulatory prowess, MSCs exhibit extensive neuroprotective actions validated through both in vitro and in vivo studies.

• Influence on Growth Factors: MSC administration influences the expression of growth factors crucial for neurogenesis, with a spotlight on brain-derived neurotrophic factor (BDNF). BDNF plays a pivotal role in cell survival, CNS cell differentiation, and the formation of synapses, primarily mediated through the PI3 kinase/Akt cell signaling route.
• Expression and Activation of Bcl-2 Gene Family: MSCs contribute to endogenous neuroprotection by upregulating members of the Bcl-2 gene family, enhancing survivability against conditions like stroke and forebrain ischemia. This protective cascade includes the upregulation of anti-apoptosis factors like survivin, preventing cell deaths in ischemic brain tissues and fostering neuronal regeneration.

Promoting Angiogenesis and Neovascularization:

MSC therapy's remarkable ability to promote angiogenesis and neovascularization emerges as a key aspect of its neuroprotective effects. The mobilization and homing of MSCs into affected areas, guided by paracrine effects and the production of angiogenic growth factors like VEGF, MCP-1, and IL6, contribute to tissue regeneration.

Recent investigations suggest that the neuroprotective effects of MSCs may be linked to mitochondrial transfer from exogenous MSCs to damaged cells. This mechanism becomes particularly crucial during oxygen deprivation in neurological disorders, helping restore cellular respiration and downregulating ROS levels.

The motor protein Miro1, situated on microtubules, regulates the trafficking of mitochondria among cells, a process upregulated by MSC administration. Additionally, the formation of tunneling nanotubes serves as a therapeutic mechanism, facilitating the delivery of functional mitochondria between MSCs and host cells.

Looking Ahead: A Synergistic Approach

As we unravel the intricate web of MSC therapy's impact on post-COVID neurological disorders, a promising future unfolds. The synergy between immunomodulation, neuroprotection, and angiogenesis positions MSCs as multifaceted allies in the fight against enduring COVID-19 effects. Stay tuned as we delve deeper into the evolving landscape of MSC therapy, unlocking its potential to reshape post-COVID care.

References:
•    Diana Esquivel MS, Rangnath Mishra MS, Ph.D, Anand Srivastava MS, Ph.D. Use of Mesenchymal Stem Cells for Mitigating the Long-Term Post COVID-19 Neurological Afflictions. Int Clinc Med Case Rep Jour. 2023;2(18):1-11.