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Gene & Protein in Disease Stem cell-based antimicrobial therapy

Table 1. Mechanism of synthetic antimicrobial peptide production within mesenchymal stem cells
Mechanism of synthetic AMP Description and explanation Key factors and considerations Reference
production within MSCs
Genetic modification MSCs are genetically engineered to express synthetic AMP Selection of appropriate gene Cheng et al., 2021 [39]
genes, typically using viral vectors or CRISPR-Cas9 technology. delivery methods
Transcription and translation The synthetic AMP gene is transcribed into mRNA in the Regulation of gene Weis et al., 2013 [40]
cell nucleus. The mRNA is, then, transported to the expression levels
cytoplasm, where ribosomes translate it into AMPs.
Post-translational Newly synthesized AMPs undergo post-translational Ensuring proper folding and Tiwari, 2019 [41]
modifications modifications, such as signal peptide cleavage, folding, and functional modifications
potential glycosylation.
Storage and secretion Processed AMPs are stored in secretory vesicles, such as Optimization of vesicle secretion Verkhratsky
exosomes, and are transported to the cell membrane for release. pathways et al., 2016 [42]
Local immune activation Released synthetic AMPs interact with pathogens by disrupting Selection of AMPs with broad- Wang et al., 2019 [43]
their membranes or interfering with intracellular processes. spectrum activity
Continuous production Engineered MSCs sustain synthetic AMP production, Monitoring long-term AMP Rai et al., 2022 [44]
resulting in a continuous release of AMPs for extended production stability
antimicrobial effects.
Site-specific migration Engineered MSCs can be guided to migrate toward infection sites Designing strategies for Zi et al., 2022 [45]
through chemotactic signals, enhancing localized AMP delivery. effective MSC migration
Regulatory considerations Genetically modified MSCs must meet safety and regulatory Compliance with ethical and Zocchi, 2019 [46]
standards for clinical applications, ensuring patient well-being. regulatory guidelines
Abbreviations: AMP: Antimicrobial peptide; MSC: Mesenchymal stem cells.

Stem cells have the potential to enhance the recruitment of Neutrophils are an essential subset of immune cells that
immune cells, thereby aiding in the eradication of microbial phagocytose and destroy invading pathogens. Human
agents and the regulation of infections . In animal embryonic stem cells have been shown to stimulate the
[47]
models pertaining to viral infections, the administration production of interferon alpha in animal models of viral
of neural stem cells has demonstrated the ability to induce infections, which inhibits viral replication and improves viral
the mobilization of immune cells toward the brain, thereby clearance . A promising method for the creation of novel
[50]
resulting in enhanced viral elimination. In animal models and effective antimicrobial therapies is stem cell-mediated
of bacterial meningitis, MSCs have been shown to improve host immunity enhancement. Stem cells have the capacity
the recruitment of immune cells to the infection site, to control immune cell generation and activity, making it
leading to increased bacterial clearance . In addition easier to treat infections and improve microbial clearance.
[48]
to their function in promoting immune cell recruitment,
stem cells can also enhance the activity of immune cells. 4. Challenges and opportunities for clinical
Analysis of the expression of major AMPs revealed that translation
one of the contributing factors to the antimicrobial activity The development of stem cell-derived treatments for
of MSC-conditioned medium against Gram-negative antimicrobial therapy is hampered by the lack of standard
bacteria was the presence of the human cathelicidin AMP, techniques for stem cell extraction, proliferation, and
hCAP-18/LL-37. Both the mRNA and protein expression delivery . The therapeutic potential of stem cell-
[51]
data illustrated an increase in LL-37 expression in MSCs based therapies may be constrained by variance in the
following bacterial challenge. By employing an in vivo aforementioned processes, which may affect stem cell
mouse model of E. coli pneumonia, the intratracheal quality and efficacy. Because different isolation methods
administration of MSCs resulted in a reduction in bacterial are used, there might be variation in the quality and
growth, as measured by colony-forming units, in both the effectiveness of the stem cells obtained from different
lung homogenates and the bronchoalveolar lavage fluid. tissues and sources. The extraction of MSCs from either
Furthermore, when MSCs were administered concurrently bone marrow or adipose tissue may lead to varying degrees
with a neutralizing antibody to LL-37, there was a of stem cell purity and differentiation capacity.
noticeable decrease in bacterial clearance .
[49]
The proliferation of stem cells in vitro is a prerequisite
MSC injection has been shown to improve neutrophil for achieving a sufficient number of cells for therapeutic
performance in animal models of bacterial infections. purposes. The quality and efficacy of stem cells can be

Volume 2 Issue 4 (2023) 6 https://doi.org/10.36922/gpd.1230