Anti-inflammatory Effects of Naïve Stem Cells Dampen Systemic/Compartmental Overreactive Immune Responses

Wolters Ech,De Munter Jpjm,De Hoo K ,Bw Kramer

doi:10.29245/2578-3009/2021/1.1205

Abstract

A cytokine release syndrome (CRS), associated with elevated circulating levels of several cytokines including interleukin (IL)-6 and interferon (IFN)-γ, might be seen in some infectious insults, for instance in severe acute respiratory syndrome (SARS) induced by Coronavirus (Cov)-2, as well as following administration of natural and bispecific antibodies and, more recently, following adoptive T-cell therapies for cancer. Normally, inflammatory conditions activate the innate and adaptive immune systems, which results in the release of cytokines, responsible for the phagocytosis of apoptotic vesicles and resolution of inflammation. Pro-inflammatory cytokines such as IL-1β, tumor necrosis factor alpha (TNFα) and, especially in chronic inflammatory diseases, autoimmune diseases, cancer and cytokine storms, IL-6 play crucial roles in inflammation. In some instances, however, this release gets out of hand, and features of overzealous immune responses (macrophage activation syndromes) might occur, leading to cytokine release syndromes (CRS) with inflammatory signs such as fever, fatigue, nausea, and sometimes secondary organ dysfunction or multi-organ failure. Apart from specific vaccines and maybe the anti-viral remdesivir and/or dexamethasone for treatment of CRS, there are no convincing disease-modifying interventions. So far, though, non-antiviral and immune-targeted interventions, also affecting non-target cells, were found associated with many side effects. A more targeted or focused approach is thus needed. Pending the site of the CRS-inducing insult, CRSs may occur systemic or compartmental. Recently, preclinical research yielded a beneficial anti-inflammatory effect of fresh naive bone marrow-derived stem cells (bm-SCs) in the treatment of various compartmental CRSs in the immune-privileged central nervous system (CNS). Therefore, it is argued that bm-SCs might also play a disease-modifying role in the systemic CRS. Bm-SCs have the advantage of targeting only the cells of interest as they are very selective in their actions. In addition, they actively move to the sight of inflammation.

Highlights

The precise reason for this excessive inflammatory response is not entirely understood but may be caused by new or specific highly pathogenic conditions, able to initiate a macrophage activation syndrome (MAS)
Intrathecal application of naïve bone marrow-derived stem cells (bm-SCs) in spinal cord injury (SCI)-rats within 24 h after the lesioning inhibited the conversion of state-2 (IRM) into state-3 (ARM) microglia, decreased neuronal apoptosis as well as the activators of IL-6 expression (TNF and IL-1β) in serum and spinal tissue when compared to the vehicle-treated animals[5,12,55]
Preclinical research suggests a beneficial effect of naive bm-derived stem cells in the treatment of this overactive inflammatory condition in the central nervous system compartment[5]. It is even in well controlled experimental models not clear, whether these anti-inflammatory effects are mediated by the resident cells if the stem cells have quickly passed their effects onto those cells

Summary

Introduction

The precise reason for this excessive inflammatory response is not entirely understood but may be caused by new or specific highly pathogenic conditions, able to initiate a macrophage activation syndrome (MAS). Inflammatory conditions activate the innate and adaptive immune systems, which results in the release of cytokines, responsible for the phagocytosis of apoptotic vesicles and resolution of inflammation. Preclinical research yielded a beneficial anti-inflammatory effect of fresh naive bone marrow-derived stem cells (bm-SCs) in the treatment of various compartmental CRSs in the immuneprivileged central nervous system (CNS).

Results

Conclusion