AccScience Publishing / GPD / Volume 2 / Issue 4 / DOI: 10.36922/gpd.1230
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Unleashing the potential of stem cells for targeted antimicrobial treatment

Ali Yetgin1,2*
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1 Toros Agri Industry and Trade Co. Inc., Research and Development Center, Mersin, Turkey
2 Cukurova University, Institute of Nature and Applied Sciences, Department of Biotechnology, Adana, Turkey
GPD 2023, 2(4), 1230 https://doi.org/10.36922/gpd.1230
Submitted: 3 July 2023 | Accepted: 20 September 2023 | Published: 6 December 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Infectious diseases continue to pose a serious threat to human health as a result of the spread of antibiotic resistance, underscoring the urgent need for new and focused therapeutic approaches. Due to their regenerative and immunomodulatory capabilities, stem cells have emerged as a potential source for the development of antimicrobial therapies. This paper reviews the potential of stem cells as a targeted strategy for combating infections, focusing on their ability to differentiate into specific cell types that can directly target and eliminate microorganisms, as well as their capacity to modulate the immune response and enhance host defenses. The article discusses the challenges and opportunities associated with the clinical implementation of antimicrobial therapies derived from stem cells. Among these obstacles are the need for uniform protocols for cell isolation, expansion, and delivery, as well as the significance of rigorous evaluations of safety and efficacy. Despite that, the application of stem cells as a targeted antimicrobial approach holds significant potential for the development of effective and enduring therapeutic interventions for infectious diseases.

Keywords
Stem cells
Antimicrobial therapy
Targeted delivery
Regenerative medicine
Host defense mechanisms
Funding
None.
References
  1. De Kraker ME, Stewardson AJ, Harbarth S, 2016, Will 10 million people die a year due to antimicrobial resistance by 2050? PLoS Med, 13(11): e1002184. https://doi.org/10.1371/journal.pmed.1002184

 

  1. Wu HH, Zhou Y, Tabata Y, et al., 2019, Mesenchymal stem cell-based drug delivery strategy: From cells to biomimetic. J Control Release, 294: 102–113. https://doi.org/10.1016/j.jconrel.2018.12.019

 

  1. Vitoria M, Granich R, Gilks CF, et al., 2009, The global fight against HIV/AIDS, tuberculosis, and malariacurrent status and future perspectives. Am J Clin Pathol, 131(6): 844–848. https://doi.org/10.1309/AJCP5XHDB1PNAEYT

 

  1. Medzhitov R, Schneider DS, Soares MP, 2012, Disease tolerance as a defense strategy. Science, 335(6071): 936–941. https://doi.org/10.1126/science.1214935

 

  1. Seo N, Akiyoshi K, Shiku H, 2018, Exosome‐mediated regulation of tumor immunology. Cancer Sci, 109(10): 2998–3004. https://doi.org/10.1111/cas.13735

 

  1. Giuliani A, Rinaldi AC, 2011, Beyond natural antimicrobial peptides: Multimeric peptides and other peptidomimetic approaches. Cell Mol Life Sci, 68: 2255–2266.

 

  1. Xu XY, Li X, Wang J, et al., 2019, Concise review: Periodontal tissue regeneration using stem cells: Strategies and translational considerations. Stem Cells Transl Med, 8(4): 392–403. https://doi.org/10.1002/sctm.18-0181

 

  1. Sun H, Zhang T, Gao J, 2022, Extracellular vesicles derived from mesenchymal stem cells: A potential biodrug for acute respiratory distress syndrome treatment. BioDrugs, 36(6): 701–715. https://doi.org/10.1007/s40259-022-00555-5

 

  1. Pellegrino E, Gutierrez MG, 2021, Human stem cell‐based models for studying host‐pathogen interactions. Cell Microbiol, 23(7): e13335. https://doi.org/10.1111/cmi.13335

 

  1. Shang F, Yu Y, Liu S, et al., 2021, Advancing application of mesenchymal stem cell-based bone tissue regeneration. Bioact Mater, 6(3): 666–683. https://doi.org/10.1016/j.bioactmat.2020.08.014

 

  1. Volponi AA, Pang Y, Sharpe PT., 2010, Stem cell-based biological tooth repair and regeneration. Trends Cell Biol, 20(12): 715–722. https://doi.org/10.1016/j.tcb.2010.09.012

 

  1. Audette RV, Lavoie-Lamoureux A, Lavoie JP, et al., 2013. Inflammatory stimuli differentially modulate the transcription of paracrine signaling molecules of equine bone marrow multipotent mesenchymal stromal cells. Osteoarthritis Cartilage, 21(8): 1116–1124. https://doi.org/10.1016/j.joca.2013.05.004

 

  1. Chen R, Hao Z, Wang Y, et al., 2022, Mesenchymal stem cell-immune cell interaction and related modulations for bone tissue engineering. Stem Cells Int, 2022: 7153584. https://doi.org/10.1155/2022/7153584

 

  1. Marrazzo P, Pizzuti V, Zia S, et al., 2021, Microfluidic tools for enhanced characterization of therapeutic stem cells and prediction of their potential antimicrobial secretome. Antibiotics (Basel), 10(7): 750. https://doi.org/10.3390/antibiotics10070750

 

  1. Deus IA, Mano JF, Custódio CA, 2020, Perinatal tissues and cells in tissue engineering and regenerative medicine. Acta Biomater, 110: 1–14. https://doi.org/10.1016/j.actbio.2020.04.035

 

  1. Rossant J. 2008, Stem cells and early lineage development. Cell, 132(4): 527–531. https://doi.org/10.1016/j.cell.2008.01.039

 

  1. Busilacchi A, Gigante A, Mattioli-Belmonte M, et al., 2013, Chitosan stabilizes platelet growth factors and modulates stem cell differentiation toward tissue regeneration. Carbohydr Polym, 98(1): 665–676. https://doi.org/10.1016/j.carbpol.2013.06.044

 

  1. Xia H, Li X, Gao W, et al., 2018, Tissue repair and regeneration with endogenous stem cells. Nat Rev Mater, 3(7): 174–193. https://doi.org/10.1038/s41578-018-0027-6

 

  1. Baldridge MT, King KY, Goodell MA., 2011, Inflammatory signals regulate hematopoietic stem cells. Trends Immunol, 32(2): 57–65. https://doi.org/10.1016/j.it.2010.12.003

 

  1. Zhu Y, Yao S, Chen L., 2011, Cell surface signaling molecules in the control of immune responses: A tide model. Immunity, 34(4): 466–478. https://doi.org/10.1016/j.immuni.2011.04.008

 

  1. Lombardo E, Van der Poll T, DelaRosa O, et al., 2015, Mesenchymal stem cells as a therapeutic tool to treat sepsis. World J Stem Cells, 7(2): 368. https://doi.org/10.4252/wjsc.v7.i2.368

 

  1. Le Blanc K, 2003, Immunomodulatory effects of fetal and adult mesenchymal stem cells. Cytotherapy, 5(6): 485–489. https://doi.org/10.1080/14653240310003611

 

  1. Zhang X, Kim TH, Thauland TJ, et al., 2020, Unraveling the mechanobiology of immune cells. Curr Opin Biotechnol, 66: 236–245. https://doi.org/10.1016/j.copbio.2020.09.004

 

  1. Bachère E, Gueguen Y, Gonzalez M, et al., 2004, Insights into the anti‐microbial defense of marine invertebrates: The penaeid shrimps and the oyster Crassostrea gigas. Immunological Rev, 198(1): 149–168. https://doi.org/10.1111/j.0105-2896.2004.00115.x

 

  1. Bush LM., Healy CP, Javdan SB, et al., 2021, Biological cells as therapeutic delivery vehicles. Trends Pharmacol Sci, 42(2): 106–118. https://doi.o10.1016/j.tips.2020.11.008

 

  1. Park J, Kim S, Lim H, et al., 2019, Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe E. coli pneumonia. Thorax, 74(1): 43–50. https://doi.org/10.1136/thoraxjnl-2018-211576

 

  1. Ahn SY, Chang YS, Kim YE, et al., 2018, Mesenchymal stem cells transplantation attenuates brain injury and enhances bacterial clearance in Escherichia coli meningitis in newborn rats. Pediatric Res, 84(5): 778–785. https://doi.org/10.1136/thoraxjnl-2018-211576

 

  1. Luarte A, Bátiz LF, Wyneken U, et al., 2016, Potential therapies by stem cell-derived exosomes in CNS diseases: Focusing on the neurogenic niche. Stem Cells İnt, 2016: 5736059. https://doi.org/10.1155/2016/5736059

 

  1. Li N, Hua J, 2017, Interactions between mesenchymal stem cells and the immune system. Cell Mol Life Sci, 74: 2345–2360. https://doi.org/10.1007/s00018-017-2473-5

 

  1. Iliopoulos JM, Layrolle P, Apatzidou DA., 2022, Microbial-stem cell interactions in periodontal disease. J Med Microbiol, 71(4): 001503. https://doi.org/10.1099/jmm.0.001503

 

  1. Esfandiyari R, Halabian R, Behzadi E, et al., 2019, Performance evaluation of antimicrobial peptide ll-37 and hepcidin and β-defensin-2 secreted by mesenchymal stem cells. Heliyon, 5(10): e02652. https://doi.org/10.1016/j.heliyon.2019.e02652

 

  1. Huang J, Wu S, Wu M, et al., 2021, Efficacy of the therapy of 5-aminolevulinic acid photodynamic therapy combined with human umbilical cord mesenchymal stem cells on methicillin-resistant Staphylococcus aureus-infected wound in a diabetic mouse model. Photodiagnosis Photodynamic Therapy, 36: 102480. https://doi.org/10.1016/j.pdpdt.2021.102480

 

  1. Kurpe SR, Grishin SY, Surin AK, et al., 2020, Antimicrobial and amyloidogenic activity of peptides. Can antimicrobial peptides be used against SARS-CoV-2? Int J Mole Sci, 21(24): 9552. https://doi.org/10.3390/ijms21249552

 

  1. Burr SP, Dazzi F, Garden OA, 2013, Mesenchymal stromal cells and regulatory T cells: the Yin and Yang of peripheral tolerance? Immunol Cell Biol, 91(1): 12–18. https://doi.org/10.1038/icb.2012.60

 

  1. Johnson V, Webb T, Dow S., 2013, Activated mesenchymal stem cells amplify antibiotic activity against chronic Staphylococcus aureus infection (P5056). J Immunol, 190(1 Suppl): 180.11. https://doi.org/10.4049/jimmunol.190.Supp.180.11

 

  1. Wang MY, Zhou TY, Zhang ZD, et al., 2021, Current therapeutic strategies for respiratory diseases using mesenchymal stem cells. MedComm (2020), 2(3): 351–380. https://doi.org/10.1002/mco2.74

 

  1. Vivarelli S, Falzone L, Leonardi GC, et al., 2021, Novel insights on gut microbiota manipulation and immune checkpoint inhibition in cancer (Review). Int J Oncol, 59(3): 75. https://doi.org/10.3892/ijo.2021.5255

 

  1. Chow L, Johnson V, Impastato R, et al., 2020, Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells. Stem Cells Transl Med, 9(2): 235–249. https://doi.org/10.1002/sctm.19-0092

 

  1. Cheng H, Zhang F, Ding Y, 2021, CRISPR/Cas9 delivery system engineering for genome editing in therapeutic applications. Pharmaceutics, 13(10): 1649. https://doi.org/10.3390/pharmaceutics13101649

 

  1. Weis BL, Schleiff E, Zerges W., 2013, Protein targeting to subcellular organelles via MRNA localization. Biochim Biophys Acta, 1833(2): 260–273. https://doi.org/10.1016/j.bbamcr.2012.04.004

 

  1. Tiwari V, 2019, Post-translational modification of ESKAPE pathogens as a potential target in drug discovery. Drug Discov Today, 24(3): 814–822. https://doi.org/10.1016/j.drudis.2018.12.005

 

  1. Verkhratsky A, Matteoli M, Parpura V, et al., 2016, Astrocytes as secretory cells of the central nervous system: İdiosyncrasies of vesicular secretion. EMBO J, 35(3): 239–257. https://doi.org/10.15252/embj.201592705

 

  1. Wang J, Dou X, Song J, et al., 2019., Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era. Med Res Rev, 39(3): 831–859. https://doi.org/10.1002/med.21542

 

  1. Rai A, Ferrão R, Palma P, et al., 2022, Antimicrobial peptide-based materials: Opportunities and challenges. J Mater Chem B, 10(14): 2384–2429. https://doi.org/10.1039/D1TB02617H

 

  1. Zi Y, Yang K, He J, et al., 2022, Strategies to enhance drug delivery to solid tumors by harnessing the EPR effects and alternative targeting mechanisms. Adv Drug Deliv Rev, 188: 114449. https://doi.org/10.1016/j.addr.2022.114449

 

  1. Zocchi ML, Vindigni V, Pagani A, et al., 2019, Regulatory, ethical, and technical considerations on regenerative technologies and adipose-derived mesenchymal stem cells. Eur J Plastic Surg, 42: 531–548. https://doi.org/10.1007/s00238-019-01571-5

 

  1. Khan A, Mann L, Papanna R, et al., 2017, Mesenchymal stem cells internalize Mycobacterium tuberculosis through scavenger receptors and restrict bacterial growth through autophagy. Sci Rep, 7(1): 15010. https://doi.org/10.1038/s41598-017-15290-z

 

  1. Doi K, Leelahavanichkul A, Yuen PS, et al., 2009, Animal models of sepsis and sepsis-induced kidney injury. J Clin Investig, 119(10): 2868–2878. https://doi.org/10.1172/JCI39421

 

  1. Krasnodembskaya A, Song Y, Fang X, et al., 2010, Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells, 28(12): 2229–2238. https://doi.org/10.1002/stem.544

 

  1. Ding J, Maxwell A, Adzibolosu N, et al., 2022, Mechanisms of immune regulation by the placenta: Role of type I interferon and interferon‐stimulated genes signaling during pregnancy. Immunol Rev, 308(1): 9–24. https://doi.org/10.1111/imr.13077

 

  1. Yao X, Wei W, Wang X, et al., 2019, Stem cell derived exosomes: MicroRNA therapy for age-related musculoskeletal disorders. Biomaterials, 224: 119492. https://doi.org/10.1016/j.biomaterials.2019.119492

 

  1. Kurtz A., 2008, Mesenchymal stem cell delivery routes and fate. Int J Stem Cells, 1(1): 1–7. https://doi.org/10.15283/ijsc.2008.1.1.1

 

  1. Herrmann IK, Wood MJ, Fuhrmann G, 2021, Extracellular vesicles as a next-generation drug delivery platform. Nat Nanotechnol, 16(7): 748–759. https://doi.org/10.1038/s41565-021-00931-2

 

  1. Dunn CM, Kameishi S, Grainger DW, et a., 2021, Strategies to address mesenchymal stem/stromal cell heterogeneity in immunomodulatory profiles to improve cell-based therapies. Acta Biomater, 133: 114–125. https://doi.org/10.1016/j.actbio.2021.03.069

 

  1. Zhang T, Lin R, Wu H, et al., 2022, Mesenchymal stem cells: A living carrier for active tumor-targeted delivery. Adv Drug Deliv Rev, 185: 114300. https://doi.org/10.1016/j.addr.2022.114300

 

  1. Teixeira MC, Carbone C, Sousa MC, et al., 2020, Nanomedicines for the delivery of antimicrobial peptides (AMPs). Nanomaterials (Basel), 10(3): 560. https://doi.org/10.3390/nano10030560

 

  1. Gao T, Huang F, Wang W, et al., 2022, Interleukin-10 genetically modified clinical-grade mesenchymal stromal cells markedly reinforced functional recovery after spinal cord injury via directing alternative activation of macrophages. Cell Mole Biol Lett, 27(1): 27. https://doi.org/10.1186/s11658-022-00325-9

 

  1. Chen CH, Bepler T, Pepper K, et al., 2022, Synthetic molecular evolution of antimicrobial peptides. Curr Opin Biotechnol, 75: 102718.

 

  1. Zhang J, Zhang W, Sun T, et al., 2022, The influence of intervertebral disc microenvironment on the biological behavior of engrafted mesenchymal stem cells. Stem Cells Int, 2022: 8671482. https://doi.org/10.1155/2022/8671482

 

  1. Cheng Y, Cao X, Qin L, 2020, Mesenchymal stem cell-derived extracellular vesicles: A novel cell-free therapy for sepsis. Front Immunol, 11: 647. https://doi.org/10.3389/fimmu.2020.00647

 

  1. Guastaldi RB, Secoli SR, 2011, Drug interactions of anti-microbial agents used in hematopoietic stem cell transplantation. Rev Lat Am Enfermagem, 19: 960–967. https://doi.org/10.1590/s0104-11692011000400015

 

  1. Lee AS, Tang C, Rao MS, et al., 2013, Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat Med, 19(8): 998–1004. https://doi.org/10.1038/nm.3267

 

  1. Lukomskyj AO, Rao N, Yan L, et al., 2022, Stem cell-based tissue engineering for the treatment of burn wounds: A systematic review of preclinical studies. Stem Cell Rev Rep, 18(6): 1926–1955. https://doi.org/10.1007/s12015-022-10341-z

 

  1. Bolli R, Hare JM, March KL, et al., 2018, Rationale and design of the CONCERT-HF trial (combination of mesenchymal and c-kit+ cardiac stem cells as regenerative therapy for heart failure). Circ Res, 122(12): 1703–1715. https://doi.org/10.1161/CIRCRESAHA.118.312978

 

  1. Hanson SE, Bentz ML, Hematti P, 2010, Mesenchymal stem cell therapy for nonhealing cutaneous wounds. Plast Reconstruct Surg, 125(2): 510–516. https://doi.org/10.1097/PRS.0b013e3181c722bb

 

  1. Mousaei Ghasroldasht M, Seok J, Park HS, et al., 2022, Stem cell therapy: From idea to clinical practice. Int J Mole Sci, 23(5): 2850. https://doi.org/10.3390/ijms23052850

 

  1. Harapanhalli RS, 2010, Food and drug administration requirements for testing and approval of new radiopharmaceuticals. Semin Nucl Med, 40(5): 364–384. https://doi.org/10.1053/j.semnuclmed.2010.05.002

 

  1. Zetterberg H, Bendlin BB, 2021, Biomarkers for Alzheimer’s disease-preparing for a new era of disease-modifying therapies. Mol Psychiatry, 26(1): 296–308. https://doi.org/10.1038/s41380-020-0721-9

 

  1. Kanie K, Sakai T, Imai Y, et al., 2019, Effect of mechanical vibration stress in cell culture on human induced pluripotent stem cells. Regen Ther, 12: 27–35. https://doi.org/10.1016/j.reth.2019.05.002

 

  1. Thirumala S, Goebel WS, Woods EJ, 2009, Clinical grade adult stem cell banking. Organogenesis, 5(3): 143–154. https://doi.org/10.4161/org.5.3.9811

 

  1. Le Blanc K, Davies LC, 2015, Mesenchymal stromal cells and the innate immune response. Immunol Lett, 168(2): 140–146. https://doi.org/10.1016/j.imlet.2015.05.004

 

  1. Zhao Y, Pu M, Zhang J, et al., 2021, Recent advancements of nanomaterial-based therapeutic strategies toward sepsis: Bacterial eradication, anti-inflammation, and immunomodulation. Nanoscale, 13(24): 10726–10747. https://doi.org/10.1039/D1NR02706A

 

  1. Qin H, Zhao A, 2020, Mesenchymal stem cell therapy for acute respiratory distress syndrome: From basic to clinics. Protein Cell, 11(10): 707–722. https://doi.org/10.1007/s13238-020-00738-2

 

  1. Lafaille FG, Harschnitz O, Lee YS, et al., 2019., Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis. Nat Med, 25(12): 1873–1884. https://doi.org/10.1038/s41591-019-0672-3

 

  1. Shi C, Zhu Y, Ran X, et al., 2006, Therapeutic potential of chitosan and its derivatives in regenerative medicine. J Surg Res, 133(2): 185–192. https://doi.org/10.1016/j.jss.2005.12.013

 

  1. Malandrakis AA, Kavroulakis N, Chrysikopoulos CV, 2022, Metal nanoparticles against fungicide resistance: Alternatives or partners? Pest Manag Sci, 78(10): 3953–3956. https://doi.org/10.1002/ps.7014

 

  1. Melkoumian Z, Weber JL, Weber DM, et al., 2010, Synthetic peptide-acrylate surfaces for long-term self-renewal and cardiomyocyte differentiation of human embryonic stem cells. Nat Biotechnol, 28(6): 606–610. https://doi.org/10.1038/nbt.1629

 

  1. Shepherd FR, McLaren JE, 2020, T cell immunity to bacterial pathogens: Mechanisms of immune control and bacterial evasion. Int J Mole Sci, 21(17): 6144. https://doi.org/10.3390/ijms21176144
Conflict of interest
The author declares no competing interests.
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