Abstract

1. Introduction

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), specifically featuring an autoimmune response resulting in inflammation, widespread primary demyelination, and progressive neurodegeneration as well as disruption of the blood–brain barrier (BBB), consequently leading to neurological dysfunction and permanent disability [1,2]. The estimated number of individuals affected by MS worldwide has increased from 2.1 million in 2008 to 2.8 million in 2020, with a greater prevalence in females [3,4]. Given that MS disease mostly targets the young group at the age of working, and given the high economic costs of the disease, it imposes a significant socioeconomic burden on societies [5,6]. Although the precise etiopathogenesis of MS is complex and still remains elusive, evidence supports the idea that an extremely complicated and multifactorial interaction between genetic, lifestyle, and environmental risk factors are of the utmost importance for MS disease initiation or progression [1,7]. Epidemiological investigations have shown that the risk of developing MS significantly increases with a raising degree of kinship, suggesting some degree of genetic susceptibility [8]. Regardless of the underlying cause, there is growing consensus that the immune system is the main culprit in MS and its animal models [9]. Among them, dysregulation or overactivation of the immune response are potentially involved in the pathogenesis and development of MS, leading to the infiltration of immune cells into the CNS and, consequently, the formation of demyelinating plaques [9]. The most prominent pathological hallmark of MS is the presence of focal demyelination, known as plaques or lesions, characterized by variable degrees of gliosis and inflammation and relative axonal preservation in the white and gray matter of the CNS [10].

Substantial insights into molecular mechanisms underlying the pathogenesis of MS and the development of therapeutic targets have emerged from studies using experimental autoimmune encephalomyelitis (EAE) [11,12]. The most commonly used model for studying autoimmune-mediated myelin degradation in MS is EAE, in which the disease can be induced (active EAE) in susceptible animals by immunization with one of the myelin-derived antigens, such as proteolipid protein, myelin oligodendrocyte glycoprotein (MOG), or myelin basic protein (MBP), leading to an immune response targeting myelin in the CNS [12,13]. In addition, EAE can also be passively induced through the adoptive transfer of activated myelin-specific helper T cells by intravenous injection into naïve animals [11].

Despite enormous progress over the past decades, there is currently no definitive treatment, and current treatment options have limitations in clinical use owing to their undesired side effects [14,15,16]. Most of the available therapeutic approaches, which are based on the prescription of immunosuppressive and immune-modulating agents, are aimed primarily at preventing the recurrence of relapses and the accumulation of disability, slowing the progression of disability as well as attenuating the symptoms [14,15,16]. Of note, these therapy options, generally, are not capable of hindering the ongoing neuronal degeneration and disease progression due to the loss of myelin [17]. Considering the limitations of conventional MS drugs, there is an urgent need to identify more effective and safe alternative therapies [16]. MSCs have garnered significant attention from scientists and clinicians as a potentially effective therapeutic intervention in various degenerative and immune cell-associated diseases due to their self-renewal capacity, multilineage differentiation, tissue and organ regeneration, and lack of immunogenicity [18]. In addition to these regeneration-promoting properties, MSCs hold potent immunomodulatory and anti-inflammatory capacity by using various mechanisms, such as extracellular vesicles (EVs) production, growth factors, mitochondrial transfer, cell contact-dependent, and soluble factors [19]. Numerous randomized controlled trials (RCTs) have shown that MSC-based investigations have increased hope for the treatment of various inflammatory and autoimmune disorders, including MS, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), inflammatory bowel disease (IBD), and Crohn’s disease (CD), with the main mechanisms being the regulation of immunity and inhibition of inflammation [20,21].

Considering the aforementioned immune-regulatory properties of MSCs, in this study, we primarily focus on the interplay between MSCs and different immune cell subsets and discuss recent advances in the use of MSCs as potential therapeutic applications in the treatment of human MS population and its animal models.

2. Pathophysiology of Multiple Sclerosis

There continues to be a rising interest in understanding the potential role of the immune response in neuroinflammatory diseases such as multiple sclerosis. MS is the most common idiopathic inflammatory and neurodegenerative disability of the CNS in young adults of presumed autoimmune etiology [22]. It is believed to be driven by an irreversible breakdown of immunological self-tolerance, an imbalance in the immunomodulatory network, and an aberrant activation of both the innate and the adaptive immune system [23]. Many defects in the functioning and regulatory mechanisms of the immune system have been detected in MS patients, but the concept that myelin-specific T cells play a central and fundamental role in generating CNS autoimmunity prevails [9].

During TCR activation in a particular cytokine milieu, naïve CD4⁺ T cells can differentiate into several functionally distinct subsets, including Th1, Th2, Treg, or Th17 effector cells, which play a critical role in mediating adaptive immunity to a variety of pathogens [24]. In EAE/MS, much evidence has been obtained in support of the concept that effector Th1 (IFN-γ)- and Th17 (IL-17)-related cytokines contribute to the inflammatory response and demyelinating lesions within the CNS, while Treg- and Th2-related cytokines have been associated with anti-inflammatory effects and the improvement of symptoms [25,26].

The major proinflammatory CD4 T-cell populations involved in the initiation and perpetuation of the disease are the autoreactive Th1 and Th17 cells [27]. Until recently, Th1 cells were thought to be the main pathogenic T cells in EAE and MS [23,28,29]. As major subsets of CD4⁺ Th cells, Th1 populations originate from stimulation with IL-12 and IFN-γ and secrete proinflammatory molecules such as IFN-γ, TNF-α, TNF-β, and IL-1β [23,28,29]. The role of Th1 lineages in MS is further supported by reports that mice lacking T-bet and signal transducer and activator of transcription 4 (STAT4), in which Th1 cell development is impaired, are completely protected from the disease [30]. Similarly, systemic administration of IFN-γ, the signature cytokine of Th1 cells, to patients with MS has been shown to aggravate the clinical disease [30,31]. It is further supported by findings that show that the adoptive transfer of IFN-γ-producing T-cell lines could induce EAE [32].

Th17 cells, another subset of CD4⁺ Th cells, have now been characterized as a unique CD4⁺ T lineage with distinct secretion of IL-17, IL-21, IL-9, IL-22, and TNF-α, of which IL-17 is the most important cytokine in Th17-mediated encephalopathy [23,33]. Recent data show that IL-6 and TGF-β are necessary during Th17 cell differentiation, while their survival and expansion are dependent on IL-21 and IL-23 [23,33]. More recently, Th17 cells have been increasingly considered to be the major driver of CNS inflammation based on evidence from animal models and patients with MS [23,34]. Several studies further confirmed the significant immunopathogenesis role of Th17 cells in MS and EAE. The frequencies of Th17 cells and IL-17 were found to increase in MS lesions [35], where they are thought to contribute to the disruption of the blood–brain barrier [33]. Moreover, infusion of Th17 cells or administration of IL-17 has been found to significantly exacerbate the severity of EAE clinical symptoms, while IL-17 or IL-17 receptor-deficient mice as well as IL-17-specific inhibition have been shown to attenuate EAE severity, indicating the central role of Th17 cells in proinflammatory responses in EAE [23,36,37].

The auto-reactive myelin-specific Th1 and Th17, which are activated in the peripheral lymph nodes, cross the blood–brain barrier (BBB) and enter the steady-state CNS, where T cells are reactivated by their lineage-defined cytokines, such as IFN-γ and IL-17, leading to demyelination, axonal damage, and spinal cord and brain lesions [38,39]. Interestingly, although both Th1 and Th17 effector cells are capable of inducing EAE, the pathological features and clinical signs may differ. IL-23-polarized T cells have been shown to promote the expression of neutrophils and granulocyte–colony-stimulating factors (CSFs), whereas macrophage-rich infiltrates and prominent NOS2 upregulation have been found to be prominent in IL–12–driven lesions [40]. In addition to these findings, IFN-γ producing Th1 subsets are required for the generation of classical EAE, whereas Th17-like cells producing IL-17-induce atypical EAE [28]. Therefore, IL-17 producing Th17 cells and IFN -γ producing Th1 cells may play complementary roles in the immunopathogenesis of EAE [28,40].

In contrast to the Th1 and Th17 subtypes, Th2 effector cells that are induced by IL-4 and produce IL-4, IL-5, IL-10, and IL-13, have been associated with inflammation reduction and improvement of symptoms in MS patients [41]. Accordingly, the IL-4-deficient C57BL/6 mice were found to be differently susceptible to EAE and developed a more severe form of the clinical disease [42], while IL-4 treatment resulted in amelioration of the clinical disease [43]. Furthermore, the clinical recovery from acute EAE appears to be associated with increased levels of IL-4 and IL-10 mRNA within the CNS [44]. Likewise, IL-4 have the ability to reduce pathological inflammation via an increase in M2 macrophages [45]. The neuroprotective effect of Th2 is also supported by the observation that treatment with the induction of MBP-specific Th2 cells alleviates demyelination and the suppression of the production of inflammatory cytokines in the CNS [43].

An intriguing relationship between the generation of inflammatory Th1 and anti-inflammatory Th2 subsets has recently been demonstrated. Th1 and Th2 responses are generally considered mutually antagonistic, as evidenced by the Th2-cytokine IL-4 and IL-10 strongly suppressing differentiation of naïve cells toward the Th1 pathway and vice versa, and the Th1-cytokines IL-12 and IFN-γ inhibit differentiation of naïve cells toward the Th2 differentiation [46,47,48] (Figure 1).

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Figure 1

Pathophysiology of multiple sclerosis (MS). MS is an autoimmune neuroinflammatory disease marked by the breakdown of immunological self-tolerance and activation of both innate and adaptive immune systems. Key players include myelin-specific T cells, particularly Th1 and Th17 cells, which drive CNS inflammation and demyelination. Th1 cells secrete proinflammatory cytokines like IFN-γ and TNF-α. Th17 cells produce IL-17 and other cytokines, contributing to blood–brain barrier disruption and CNS lesions. Regulatory T cells (Treg) and Th2 cells counteract inflammation, promoting symptom improvement. Th1 and Th17 cells play complementary roles in MS pathogenesis, while Th2 cells, induced by IL-4, produce anti-inflammatory cytokines (IL-4, IL-10), reducing inflammation and improving symptoms. CD8⁺ T cells (CTLs) predominate in CNS lesions, secreting proinflammatory cytokines (TNFα, IFN-γ) and exhibiting cytotoxicity via perforin and granzyme. They can also produce IL-10, suggesting a regulatory role. B cells contribute to MS pathogenesis through antigen presentation. BBB: blood–brain barrier; TH: T helper cell; TCR: T cell receptor; MHC: major histocompatibility complex; CTL: cytotoxic T lymphocyte; IL: interleukin; TNF: tumor necrosis factor; IFN: interferon.

As master regulators of immune responses, CD4⁺ regulatory T cells (Tregs) expressing the FoxP3 transcription factor have the ability to modulate the function of effector T cells, maintaining immunological homeostasis and preventing autoimmunity, thereby serving a protective function in autoimmune diseases [24]. IL-10 and transforming growth factor-β (TGF-β), the main secreting productions of Treg, have been shown to limit pathological autoreactive immune responses and the cascade of proinflammatory cytokines activation [49]. Notably, decreased frequencies and functionally impaired Tregs cells have been detected in MS lesions, and have also been found to correlate with an exacerbation of disease symptoms [24]. Besides, several studies have described that the transfer of Treg cells significantly attenuates EAE symptoms or pathological severity, while Treg depletion has been reported to exacerbate EAE severity, accompanied by increased production of proinflammatory cytokines and proliferation of autoreactive effector T cells [50,51].

In addition to the abovementioned cells, over the last decade, research has shifted the focus of attention toward CD8⁺ T cells as evidence increasingly demonstrates that CD8⁺ T cells predominate over CD4⁺ T cells in CNS lesions of MS patients [52,53]. CD8⁺ T cells, also known as cytotoxic T lymphocytes (CTL), are characterized by their ability to secrete high levels of proinflammatory cytokines, such as TNFα and IFN-γ, and cytotoxic properties through perforin and granzyme and Fas pathways [54,55]. Cytotoxic T cells are implicated in the pathogenesis of MS during the relapse phases and in the chronic phase [45,56]. Under inflammatory conditions, most CNS resident cells including oligodendrocytes, astrocytes, and neurons express MHC class I antigens, making them potential targets for cytotoxic CD8⁺ T cells [52,57]. Intriguingly, the recent growing body of literature suggests that CD8⁺ T cells not only induce or aggravate tissue destruction in the CNS in murine and human autoimmune disorders, but also has regulatory properties and is involved in suppressing disease progression and/or severity by producing immunosuppressive cytokine IL-10 [52,54,58]. Therefore, CD8⁺ T cells can act as a double-edged sword and further research is needed to elucidate the roles of these subsets in MS.

Although much focus on MS pathology and its model animals has centered on autoreactive T cells, remarkable evidence from patients with MS points to a role played by B cells in disease pathogenesis in various ways, including antigen-presenting cells and production of proinflammatory cytokines and/or autoantibodies [9]. One of the most compelling findings highlighting the major role of B cells in the disease has been the B cell depletion efficiently suppressing inflammatory disease activity [23,59].

Since MS is driven by the excessive activity of autoreactive Th1 and T17 cells and is suppressed by Th2 and Treg cells, the development of novel therapeutic approaches based on manipulating immune cells, in particular T cell subtypes, can be very promising in the therapy of immune-mediated and inflammatory disorders such MS [25].

3. Mesenchymal Stem Cells: Characteristics and Mechanisms of Action

MSCs are a group of nonhematopoietic stem cells with high self-renewal ability that were initially isolated from bone marrow and subsequently identified in many other tissues, such as adipose tissue, epidermis, umbilical cord blood, and the periendothelial area [60,61]. They are characterized by their extensive capacity to differentiate into cells indicative of various mesenchymal lineages, such as osteoblasts, chondrocytes, fibroblasts, and adipocytes in response to appropriate stimuli [60,61]. According to the tissue of origin, MSCs can express a wide range of surface markers and cytokine profiles [62]. Phenotypically, the common characterization markers of MSCs are CD105, CD90, and CD73 and the absence of hematopoietic progenitor cells markers such as CD45, CD34, CD14, CD19, and HLA class II [62]. Owing to paracrine potentials, ease of accessibility and separation, long-term ex vivo proliferation, differentiation multipotency, and their anti-inflammatory action, they are considered a desirable cell source in regenerative medicine [63,64]. Recently, MSC-related cell therapy has been shown to be a promising therapeutic strategy in a broad panel of immune disorder-related diseases and degenerative diseases such as MS, mainly attributable to the neuroprotective and immunomodulatory effects of these cell.

Intensive research has been undertaken to unravel the mechanisms by which MSCs mediate their immunosuppressive properties. An increasing number of studies have shown that immunoregulation by MSCs is mediated directly by two distinct mechanisms: interactions with immune cells through cell-to-cell contact and soluble factors, including nitric oxide (NO), hepatocyte growth factor (HGF), fibroblast growth factor (FGF), indoleamine-pyrrole 2,3-dioxygenase (IDO), PGE2, IL-4, IL-10, TNF-α, and TGF-β1, all of which are involved in the suppression of proinflammatory signaling and augmentation of regulatory networks [65,66].

The interplay between MSCs and immune cells is being investigated in numerous clinical trials. The MSCs exert an immunomodulatory function on both the innate and adaptive immune system such as T, B, NK cells, and DCs, making them beneficial for treating conditions caused by abnormal immune activation [67]. The evidence is increasingly indicating that MSCs are also capable of inducing immune cells with more anti-inflammatory or tolerant phenotypes [68], accompanied by a shift from pathogenic inflammatory Th1 and Th17 cell subtypes to anti-inflammatory Th2 and Treg cells [14,69,70,71]. In response to inflammatory mediators, MSCs undergo a process of selective migration to injury and inflammation using cell adhesion molecules and receptors of cytokines and subsequently stimulate potent immunomodulatory and anti-inflammatory activities [72]. Under inflammatory stimulants, MSCs are able to promote PD-L and FasL, which repress pathogenic CD4⁺T cell responses and cause direct killing of activated T cells, respectively [73]. Consistent with these observations, a number of studies have suggested that MSCs repress the inflammation process, partly by downregulating the production of proinflammatory cytokines produced by Th1 and Th17 such as IL-17, IL-1β, IL-6, IL-21, IL-22, IFN-γ, TNF-α, and IL-12, while enhancing the production of anti-inflammatory mediators produced by Th2 and Treg cells including IL- 5, IL-4, IL-10, and TGF-β [65,67,74,75,76] (Figure 2).

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Figure 2

The interplay between MSCs and immune cells. MSCs modulate immune responses by interacting with T, B, NK cells, and DCs. They promote anti-inflammatory phenotypes (Th2, Treg) and inhibit proinflammatory phenotypes (Th1, Th17). MSCs suppress cytotoxic T cell (CTL) proliferation and function, inhibiting B cell differentiation and antibody production. They also modulate dendritic cell (DC) maturation and function, polarize macrophages from the M1 to the M2 phenotype, and suppress NK cell activity through cytokines. NK: natural killer cells; IL: interleukin; IFN: interferon; MQ: macrophage; CTL: cytotoxic T lymphocyte; T-reg: regulatory T cell; Th: T helper cell; TGF: transforming growth factor; PGE: prostaglandin E; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; STAT3: signal transducer and activator of transcription 3; HLA: human leukocyte antigen.

Besides CD4⁺ helper T cells, CD8⁺ cytotoxic T cells are also susceptible to the suppressive activity of MSC. Several lines of evidence have demonstrated that MSCs could inhibit the proliferation and cytotoxic function of CTLs and modulate their cytokine production through TGF-β and IL-6 [67,72]. Most importantly, they can inhibit the differentiation of cytotoxic T lymphocyte precursor cells (CTL-P) into CTL effector cells through the secretion of suppressive factors [77].

The humoral immune system may be affected by the immunosuppressive properties of MSCs. It has been well documented that both human and murine MSCs could suppress B cell differentiation, maturation, and plasma cell differentiation, as well as antibody production [78,79,80]. Moreover, they promote the polarization of the B cell phenotype toward the B regulatory cells (Bregs) phenotype, which releases IL-10, possesses anti-inflammatory and immunoregulatory properties, and modulates the immune environment homeostasis [81].

MSCs are reported to inhibit the immune response by modulating antigen presentation by DCs. Growing evidence supports that MSCs not only suppress conventional DCs, but also induce regulatory DCs [67]. Strikingly, a number of studies have shown the capacity of MSCs to disrupt the maturation and function of DC through the downregulation of MHC class II molecules and costimulatory molecules, resulting in the production of the nonfunctional T cells [67,82,83]. In addition, MSCs have been shown to polarize macrophages from a proinflammatory M1 profile toward a neuroprotective and anti-inflammatory M2 profile through the NF-κB and STAT3 pathways and secrete soluble factors, leading to the suppression of proinflammatory cytokines secretion [84,85]. Furthermore, it has been demonstrated that MSCs are capable of suppressing NK-cell proliferation, cytokine secretion, and cytotoxicity through immunosuppressive secretors, such as PGE2, TGF-β, and sHLA-G [86].

In addition to these immunomodulatory functions, MSCs also have immunosupportive capacities. It is worth noting that MSCs have also been shown to attenuate microgliosis and astrogliosis, as well as demyelination, through the secretion of neuroprotective factors [14,87]. Another intriguing feature of MSCs is their ability to evade immune recognition and even actively inhibit immune responses. This hypoimmunogenic or immune-privileged property is attributable to the low expression of class II major histocompatibility complex (MHC-II) and costimulatory molecules such as CD40, CD80, and CD86 in their cell surface [70].

However, MSCs may exert differential functions according to certain mediators present in their microenvironment, as several conflicting findings have shown that MSCs can both fortify and restrain the inflammation under several conditions. In fact, the immunosuppressive ability of MSCs is dependent upon the types and strengths of the inflammatory signals they receive [80,88].

4. Preclinical Studies Investigating MSC Therapy in MS

4.1. Overview of Preclinical Studies Using Animal Models of MS

Several animal tests and clinical investigations have found stem cell treatment to cure or prevent CNS damage [89]. It has been demonstrated that bone-marrow-derived mesenchymal stem cells (BM-MSCs) have immunomodulatory and regenerative abilities [90]. Therefore, a novel treatment strategy for autoimmune diseases, such as MS, has been suggested: the transplantation of BM-MSCs in an EAE model [90]. Research has demonstrated that BM-MSCs can decrease the quantity of effector T cells in BM-MSC-transplanted EAE mice while increasing the amount of regulatory T cells (Treg) in the mice, inhibiting effector T cells and lessening EAE [90,91]. Furthermore, it has been proposed that BM-MSCs can drive macrophages in the spleen to polarize from the M1 type to the M2 type and reduce their production of TNF-α, a phenomenon which will relieve EAE [90]. BM-MSC-transplanted EAE mice have been found to express more anti-inflammatory cytokines like TGF-β and IL-10, while producing fewer inflammatory cytokines like IL-1β and IFN-γ [92] (Figure 3).

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Figure 3

The therapeutic effects of mesenchymal stem cells (MSCs) in the experimental autoimmune encephalomyelitis (EAE) model. The immune modulatory signs that have been observed in EAE animal models that received MSCs derived from various tissues, including adipose, bone marrow, and dental, include an increase in CD4⁺ CD25⁺ FoxP3⁺Treg differentiation from naïve T cell against a decrease in Th1 and Th17 induction. This has led to a rise in the production of anti-inflammatory cytokines like TGF-β and IL-10 and a reduction in the production of proinflammatory cytokines like IL-17, IL-1β, and IFN-$\gamma$. Furthermore, MSCs can reduce TNF-α production (not shown in the image) by causing M1 macrophages to polarize into M2 macrophages, alleviating EAE.

Our previous study’s findings suggest that exosomal miRNAs may be useful in treating EAE [93]. Delivery of BM-MSCs was demonstrated to diminish miR-21, miR-223, and miR-155 and increase miR-146, a phenomenon which was coupled with a decrease in Th1- and Th17-associated cytokines such as IFN-γ, IL-17, and IL-12 [93]. The study also showed that there was an increase in TGF-β and IL-10 expression [93]. Another study conducted by our group revealed that injecting synergic and allogeneic adipose-derived mesenchymal stem cells may improve the clinical score of EAE mice. This improvement was correlated with a decrease in the expression of inflammatory cytokines and an increase in anti-inflammatory cytokines in the spleen and central nervous system [94].

Studies have indicated that conditioned media produced from MSCs can contribute to the healing of EAE by combining immune inhibition and myelination induction [95]. Rajan and colleagues have shown that preconditioning neurons with human periodontal ligament mesenchymal stem cells (hPDLSC-CM) inhibits TLR-4 activation in the lipopolysaccharide (LPS)-activated mice motoneurons, preventing cell death linked to LPS activation [96]. Furthermore, it has been shown that the levels of neuronal growth factors and trophic factors Nestin, NGF, NFL-70, and GAP43 are elevated in the neurons preconditioned with hPDLSC-CM. This finding demonstrates that hPDLSC-CM plays a role in promoting neuronal growth [96]. Through two different routes, it has been demonstrated that MSCs may enhance the myelinating capacity and engraftment of allogenic oligodendrocyte progenitors in demyelinated mice. First, by producing anti-inflammatory cytokines that diminish microglia and astrocytosis, and, second, by inducing trophic support through the release of growth factors like IGF-1 that facilitate the development of progenitor cells of oligodendrocytes into myelinating oligodendrocytes [97].

Additionally, it has been shown that IFN-γ-primed human MSCs may suppress the expression of Th17-specific transcription factors STAT3 and ROR-γt while increasing the amount of Treg transcription factor Foxp3, which affects the Th17/Treg balance and reduces inflammation, therefore curing EAE in animal models [98].

5. Clinical Trials Evaluating MSC Therapy for MS

6. Challenges and Future Directions

MSC therapies have been the subject of more than 300 clinical trials, involving patients with autoimmune and degenerative conditions among others. Although MSC therapies have made enormous advances in recent decades, several challenges remain to be overcome.

MSCs have received regulatory approval in certain countries due to their generally acceptable safety profile and potential therapeutic effects in specific clinical contexts. However, with studies reporting inconsistent results, the true safety and clinical efficacy of MSC therapy have yet to be demonstrated, and a better knowledge of limits could lead to broader clinical implementation of safe cell therapies while avoiding damaging strategies.

7. Conclusions

The emerging research on the role of immune responses in neuroinflammatory diseases such as MS highlights a complex interplay between various T cell subsets, including Th1, Th17, Th2, and Treg cells, as well as the involvement of B cells and CD8⁺ T cells. The promising results from preclinical studies underscore the potential of MSCs in modulating these immune responses and providing neuroprotection. MSCs, with their ability to interact with various immune cells and release anti-inflammatory cytokines, offer a novel therapeutic approach for MS. Their capacity to shift the balance from proinflammatory Th1 and Th17 responses toward more anti-inflammatory Th2 and Treg responses is particularly noteworthy. Clinical trials have shown that MSC therapy is generally safe and holds promise with respect to the improvement of patient outcomes, although further research is needed to optimize treatment protocols and address challenges such as dose determination and potential transplant rejection. The ongoing exploration of MSCs as a treatment modality for MS presents a significant opportunity to develop more effective therapies for this debilitating condition. Future research should focus on refining MSC characterization, understanding their interactions with the immune system, and establishing robust clinical guidelines to fully harness their therapeutic potential.

Funding Statement

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare no conflicts of interest.

Footnotes

References