Page 13 - GPD-2-4
P. 13

Gene & Protein in Disease                                              Stem cell-based antimicrobial therapy



            of differentiating into macrophages, which are essential   an  anti-inflammatory response, and reducing tissue
            immune cells responsible for phagocytosis and elimination   damage brought on by inflammation. It has been noted that
            of foreign pathogens . In addition, stem cells have the   immune cells that cause tissue inflammation and injury
                             [29]
            ability to produce and release AMPs and proteins, which   can be inhibited by stem cells. T-cells, a crucial component
            can  directly  inhibit  the  proliferation  of microorganisms   of  immune  cells  that  significantly  contribute  to  tissue
            or cause their demise. Peptides and proteins are capable   injury in autoimmune and inflammatory disorders, can be
                                                                                         [34]
            of  disrupting  the cell membranes of  microorganisms,   inhibited in their activity by MSCs . MSCs have the capacity
            impeding the  replication of  microbial DNA,  preventing   to reduce tissue damage and enhance tissue regeneration by
            protein synthesis, and interfering with the physiology of   regulating the activity of these cells. Activation of MSC using
            micro-organisms as a whole.                        Toll-like receptor (TLR) ligands exhibited a noteworthy
                                                               augmentation in the generation of the AMP called CXCL10,
              The ability of human embryonic stem cells to produce
            AMPs with inhibitory effects against bacteria, fungi, and   while simultaneously suppressing bacterial proliferation
                                                               in an artificial environment. Among the TLR agonists
            viruses has been demonstrated . However, the ability of   examined in vitro, poly(I:C), a TLR3 agonist, displayed the
                                     [30]
            defensins, cathelicidins, and histatins to inhibit microbial   greatest efficacy. In the context of chronic S. aureus infection,
            growth and disrupt microbial cell membranes remain   MSC activation with poly(I: C) elicited a reduction in the
            contentious. Similarly, MSCs are capable of releasing   quantitative assessment of bacterial presence .
                                                                                                 [35]
            cathelicidin, an AMP that eliminates microbes by interfering
            with their cell membranes . It is possible to manipulate   In addition, stem cells can promote the development
                                 [31]
            stem cells to generate artificial AMPs that target specific   of regulatory T-cells, which are essential for maintaining
            microorganisms. For example, scientists have manipulated   immunological homeostasis and preventing unnecessary
            MSCs to generate a synthetic AMP that is effective against   immune activation. Regulatory T-cells have the ability to
            methicillin-resistant  Staphylococcus aureus, a variant of   inhibit the function of other immune cells that participate
            S. aureus resistant to many conventional antibiotics. The   in the inflammatory response and cause harm to tissues,
            modified MSCs showed efficient bactericidal action against   while also facilitating the process of tissue repair. MSCs
            methicillin-resistant S. aureus in both in vitro and in vivo   have demonstrated the ability to enhance the generation
            animal infection models . Nonetheless, the antibacterial   of regulatory T-cells and mitigate inflammation in animal
                               [32]
            abilities of stem cells are complex and situational.  models of bacterial pneumonia, resulting in enhanced
                                                               bacterial elimination and pulmonary performance .
                                                                                                           [36]
              As compact protein molecules, AMPs perform a vital   Studies conducted on animal models of viral encephalitis
            function in the immune defense mechanism of the body   have demonstrated that the transplantation of neural stem
            by combating various pathogens, such as bacteria, viruses,   cells can effectively mitigate inflammation and facilitate
            and fungi. Immune cells represent the natural source of   the regeneration of neurons. The manipulation of the host’s
            these peptides. Driven by the desire for more controllable   immune response through stem cells presents a hopeful
            production of AMPs, recently, there has been a surge in the   direction for the advancement of innovative and efficacious
            studies regarding the feasibility of artificially synthesizing   antimicrobial treatments . Stem cells have the potential
                                                                                   [37]
            AMPs as potential therapeutic agents. These peptides are   to regulate infections and facilitate tissue regeneration by
            designed to imitate natural AMPs and can exterminate or   inducing an anti-inflammatory response and mitigating
            hinder the proliferation of harmful microorganisms. The   tissue damage. Systemic administration of activated MSCs
            human body houses a store of MSCs, which are present in   to mice with pre-existing  S. aureus biofilm infections
            different tissues such as adipose and bone marrow. MSCs   resulted in a notable reduction in bacterial quantities at
            can  generate  a  range  of  bioactive  molecules,  including   the site of the wound, thus leading to an enhancement in
            AMPs. Researchers are studying the concept of genetically   wound healing, particularly when executed in conjunction
            engineering MSCs to generate artificial AMPs . The   with antibiotic treatment .
                                                    [33]
                                                                                   [38]
            introduction of these engineered MSCs to patients could   Table 1 provides an organized breakdown of the
            pave the way for a novel therapeutic approach in combating   key steps involved in the mechanism of synthetic AMP
            infections. These cells would continuously synthesize and   production within MSCs. It highlights how genetic
            discharge synthetic AMPs, amplifying the body’s capability   modification, transcription, translation, and cellular
            to fight infections.
                                                               processes contribute to the production and release of
              Stem cells have the ability to alter the host’s immune   AMPs, ultimately leading to the antimicrobial effect. The
            response in a number of ways, which helps in the   activation of cytokines and chemokines by stem cells can
            treatment of infections. Stem cells have the capacity to   augment the immune response of the host, leading to the
            control cytokine and chemokine production, promoting   recruitment of immune cells to the location of infection.


            Volume 2 Issue 4 (2023)                         5                        https://doi.org/10.36922/gpd.1230
   8   9   10   11   12   13   14   15   16   17   18