Beyond Regeneration: Mesenchymal Stem Cells as Antimicrobial Agents in Burn Wound Healing
-
Behnam Poureslamfar
,
Sahar Yadegari
,
Kanzur Rahman Mufazzil
,
Mahmood Karimi
,
Behnaz Misaii
,
Faezeh Tehrani Niya
,
Reza Yekani
,
Forouzan Esmaeili Dahaj
,
Ali Abesi
,
Mona Mohammadzadeh
Abstract
Burn injuries present a considerable global health challenge, characterised by intricate healing processes that are exacerbated by infection and impaired tissue regeneration. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their regenerative, immunomodulatory, and antimicrobial properties. MSCs have been shown to secrete AMPs such as LL-37 and hepcidin, which have been found to directly target pathogens including Pseudomonas aeruginosa and Staphylococcus aureus. In addition to this direct antimicrobial action, MSCs have also been observed to modulate immune responses through the secretion of cytokines such as IL-10 and TGF-β. Their regenerative effects include the promotion of angiogenesis, re-epithelialization, and extracellular matrix (ECM) remodelling via growth factors such as EGF, KGF, and SDF-1. In-vitro and animal studies have demonstrated enhanced wound closure, reduced scarring, and improved antimicrobial efficacy through novel delivery systems such as hydrogels and preconditioning strategies. As demonstrated by clinical trials, the treatment has been shown to facilitate accelerated healing and reduced reliance on antibiotics. However, challenges such as the heterogeneity of mesenchymal stem cells (MSCs), optimisation of dosing, and safety concerns (e.g. coagulopathy, systemic inflammation) persist. Emerging technologies, including synthetic gene circuits, microbiome-targeted engineering, and bioresponsive delivery systems, offer solutions to enhance the efficacy of MSCs. This review emphasises the potential of MSCs to transform the management of burn wounds, while underscoring the necessity for standardised protocols and advanced engineering to surmount translational barriers.
1. Kumar M., Mahmood S, Mandal UK, An updated account on formulations and strategies for the treatment of burn infection-A review. Current Pharmaceutical Design 2022; 28(18):1480-92.
2. Wang Y, Beekman J, Hew J, et al. Burn injury: challenges and advances in burn wound healing, infection, pain and scarring. Adv Drug Del Rev 2018; 123:3-17.
3. Brandenburg KS, Weaver AJ, Karna SR, et al. The impact of simultaneous inoculation of Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans on rodent burn wounds. Burns 2021; 47(8):1818-32.
4. Kopecki Z. Development of next-generation antimicrobial hydrogel dressing to combat burn wound infection. Biosci Rep 2021; 41(2):BSR20203404.
5. Wu S, Sun S, Fu W, et al. The role and prospects of mesenchymal stem cells in skin repair and regeneration. Biomed 2024; 12(4):743.
6. Yang X, Yang R, Chen M, et al. KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats. BMJ Open Diabetes Res Care 2020; 8(1).
7. Liu Z, Yang J, Chen Y, et al. P311 facilitates the angiogenesis and wound healing function of MSCs by increasing VEGF production. Front Immunol 2022; 13:821932.
8. Sousa AB, Águas AP, Barbosa MA, et al. Immunomodulatory biomaterial-based wound dressings advance the healing of chronic wounds via regulating macrophage behavior. Regen Biomat 2022;9:rbac065.
9. Wang M, Xu X, Lei X, et al. Mesenchymal stem cell-based therapy for burn wound healing. Burn Trauma 2021; 9:tkab002.
10. Urashima A, Sanou A, Yen H, et al. Enterohaemorrhagic Escherichia coli produces outer membrane vesicles as an active defence system against antimicrobial peptide LL‐37. Cell Microbiol 2017; 19(11):e12758.
11. Zheng J, Liu X, Xiong Y, et al. AMXT-1501 targets membrane phospholipids against Gram-positive and-negative multidrug-resistant bacteria. Emerg Microbe Infec 2024; 13(1):2321981.
12. Bitterlich LM, Tunstead C, Hogan AE, et al. Mesenchymal stromal cells can block palmitate training of macrophages via cyclooxygenase-2 and interleukin-1 receptor antagonist. Cytother 2025; 27(2):169-80.
13. Zheng G, Ge M, Qiu G, et al. Mesenchymal stromal cells affect disease outcomes via macrophage polarization. Stem Cell Int 2015; 2015(1):989473.
14. Elshamy AA, Kamal SK, Mahmoud MT, et al. Recent insights on phage therapy against multidrug-resistant Acinetobacter baumannii. AMB Express 2025; 15(1):1-16.
15. Long X, Yuan Q, Tian R, et al. Efficient healing of diabetic wounds by MSC-EV-7A composite hydrogel via suppression of inflammation and enhancement of angiogenesis. Biomat Sci 2024; 12(7):1750-60.
16. Česnik AB, Švajger U. The issue of heterogeneity of MSC-based advanced therapy medicinal products–a review. Front Cell Dev Bio 2024; 12:1400347.
17. Liu J, Xu Z, Yu J, et al. MiR-146a-5p engineered hucMSC-derived extracellular vesicles attenuate dermatophagoides farinae-induced allergic airway epithelial cell inflammation. Front Immunol 2024; 15:1443166.
18. Iwatake M, Nagamura-Inoue T, Doi R, et al. Designer umbilical cord-stem cells induce alveolar wall regeneration in pulmonary disease models. Front Immunol 2024; 15:1384718.
19. Bártolo I, Reis RL, Marques AP, et al. Keratinocyte growth factor-based strategies for wound re-epithelialization. Tissue Eng 2022; 28(3):665-76.
20. Stewart AN, Matyas JJ, Welchko RM, et al. SDF-1 overexpression by mesenchymal stem cells enhances GAP-43-positive axonal growth following spinal cord injury. Restor Neurol Neurosci 2017; 35(4):395-411.
21. Wu Q, Xu WD, Huang AF. Role of angiopoietin-2 in inflammatory autoimmune diseases: A comprehensive review. Int Immunopharmacol 2020; 80:106223.
22. Slautin V, Konyshev K, Gavrilov I, et al. Fucoxanthin enhances the antifibrotic potential of placenta-derived mesenchymal stem cells in a CCl4-induced mouse model of liver. Curr Stem Cell Res Ther 2024; 19(11):1484-96.
23. Xie C, Mondal DK, Ulas M, et al. Oncosuppressive roles of decorin through regulation of multiple receptors and diverse signaling pathways. Am J Physiology 2022; 322(3):C554-C66.
24. Fang S, Xu C, Zhang Y, et al. Umbilical cord-derived mesenchymal stem cell-derived exosomal microRNAs suppress myofibroblast differentiation by inhibiting the transforming growth factor-β/SMAD2 pathway during wound healing. Stem Cells Trans Med. 2016; 5(10):1425-39.
25. Manzoor T, Farooq N, Sharma A, et al. Exosomes in nanomedicine: a promising cell-free therapeutic intervention in burn wounds. Stem Cell Res Ther 2024; 15(1):355.
26. Kuang L, Zhang C, Li B, et al. Human keratinocyte-derived exosomal MALAT1 promotes diabetic wound healing by upregulating MFGE8 via microRNA-1914-3p. Int J Nanomed 2023:949-70.
27. Rangatchew F, Vester-Glowinski P, Rasmussen BS, et al. Mesenchymal stem cell therapy of acute thermal burns: a systematic review of the effect on inflammation and wound healing. Burns 2021; 47(2):270-94.
28. Mirshekar M, Afkhami H, Razavi S, et al. Potential antibacterial activity and healing effect of topical administration of bone marrow and adipose mesenchymal stem cells encapsulated in collagen-fibrin hydrogel scaffold on full-thickness burn wound infection caused by Pseudomonas aeruginosa. Burns 2023; 49(8):1944-57.
29. Smolinska V, Harsanyi S, Bohac M, et al. Exploring the three-dimensional frontier: advancements in MSC spheroids and their implications for breast cancer and personalized regenerative therapies. Biomed 2023; 12(1):52.
30. da Silva KN, Marim FM, Rocha GV, et al. Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infection. Stem Cell Res Ther 2025; 16(1):15.
31. Enayati S, Halabian R, Saffarian P, et al. Nisin-preconditioned mesenchymal stem cells combatting nosocomial Pseudomonas infections. Regen Ther 2024; 26:161-9.
32. Choudhury S, Madhu Krishna M, Sen D, et al. 3D Porous Polymer Scaffold-Conjugated KGF-Mimetic Peptide Promotes Functional Skin Regeneration in Chronic Diabetic Wounds. ACS Appl Mat Interfaces 2024; 16(29):37418-34.
33. Chouhan D, Lohe TU, Thatikonda N, et al. Silkworm silk scaffolds functionalized with recombinant spider silk containing a fibronectin motif promotes healing of full-thickness burn wounds. ACS Biomat Sci Eng 2019; 5(9):4634-45.
34. Saheli M, Bayat M, Ganji R, et al. Human mesenchymal stem cells-conditioned medium improves diabetic wound healing mainly through modulating fibroblast behaviors. Arch Dermatol Res 2020; 312(5):325-36.
35. Palmieri TL. Emerging therapies for full-thickness skin regeneration. J Burn Care Res 2023; 44:S65-S7.
36. Li CY, Wu XY, Tong JB, et al. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Res Ther 2015; 6:1-13.
37. Redondo-Castro E, Cunningham CJ, Miller J, et al. Changes in the secretome of tri-dimensional spheroid-cultured human mesenchymal stem cells in vitro by interleukin-1 priming. Stem cell Res Ther 2018; 9:1-11.
38. Fu Y, Li J, Zhang Z, et al. Umbilical cord mesenchymal stem cell‐derived exosomes alleviate collagen‐induced arthritis by balancing the population of Th17 and regulatory T cells. FEBS lett 2022; 596(20):2668-77.
39. De Servi B, Orlandini A, Caviola E, et al. Amino acid and hyaluronic acid mixtures differentially regulate extra cellular matrix genes in cultured human fibroblasts. J Biological Reg Homeos Agents 2018; 32(3):517-27.
40. Chen H, Zhao H. Resveratrol enhances the efficacy of combined BM-MSCs therapy for rat spinal cord injury via modulation of the Sirt-1/NF-κB signaling pathway. Neurochem Res 2025; 50(1):12.
41. Putra I, Shen X, Anwar KN, et al. Preclinical evaluation of the safety and efficacy of cryopreserved bone marrow mesenchymal stromal cells for corneal repair. Trans Vision Sci Technol 2021; 10(10):3-.
42. Xu Y, Wang XS, Zhou XL, et al. Mesenchymal stem cell therapy for liver fibrosis need “partner”: Results based on a meta-analysis of preclinical studies. World J Gastroenterol 2024; 30(32):3766.
43. Hermeto LC, DeRossi R, Oliveira RJ, et al. The efficacy of topical insulin application on rat model with burn wounds treated with adipose-derived stem cells. Int J Burns Trauma 2020; 10(6):296.
44. Pyun DG, Choi HJ, Yoon HS, et al. Polyurethane foam containing rhEGF as a dressing material for healing diabetic wounds: synthesis, characterization, in vitro and in vivo studies. Colloids Surfaces 2015; 135:699-706.
45. Incontri Abraham D, Gonzales M, Ibarra A, et al. Stand alone or join forces? Stem cell therapy for stroke. Expert Opinion Bio Ther 2019; 19(1):25-33.
46. Madrigal M, Fernández PL, Lleonart R, et al. Comparison of cost and potency of human mesenchymal stromal cell conditioned medium derived from 2-and 3-dimensional cultures. Bioeng 2023; 10(8):930.
47. Zahorec P, Sarkozyova N, Ferancikova N, et al. Autologous mesenchymal stem cells application in post-burn scars treatment: a preliminary study. Cell Tissue Banking 2021; 22:39-46.
48. Kumar A, Ramesh S, Kumar V, et al. Human second-trimester fetal liver-derived mesenchymal stromal cells are more effective than adult bone marrow MSCs for their superior growth kinetics, immunomodulatory, and osteogenic potential. Tissue Cell 2025; 95:102859.
49. Aslam S, Khan I, Jameel F, et al. Umbilical cord-derived mesenchymal stem cells preconditioned with isorhamnetin: potential therapy for burn wounds. World J Stem Cells 2020; 12(12):1652.
50. Frescaline N, Duchesne C, Favier M, et al. Physical plasma therapy accelerates wound re‐epithelialisation and enhances extracellular matrix formation in cutaneous skin grafts. J Path 2020; 252(4):451-64.
51. Rady D, Abbass MM, El-Rashidy AA, et al. Mesenchymal stem/progenitor cells: the prospect of human clinical translation. Stem Cells Int 2020; 2020(1):8837654.
52. Rolland TJ, Zahra S, Cucinotta D, et al. Mesenchymal stem cell-derived extracellular vesicles mitigate immune cell activation in an in vitro model of post-resuscitation inflammation. bioRxiv 2025; 13.637856.
53. Zhang J, Li LB, Qiu Z, et al. Intravenous injections of human mesenchymal stromal cells modulated the redox state in a rat model of radiation myelopathy. Evid Compl Alt Med. 2015; 2015(1):432369.
54. O'Rourke B, Nguyen S, Tilles AW, et al. Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application. Stem Cells Trans Med 2021; 10(6):883-94.
55. Schriner JB, Triolo F, Gill BS, et al. Low molecular weight heparin decreases pro-coagulant activity in clinical MSC products. Cytotherapy 2024; 26(2):194-200.
56. Arshad T, Mundrathi V, Perez VE, et al. Topical probiotic hydrogels for burn wound healing. Gels 2024; 10(9):545.
57. Eylert G, Dolp R, Parousis A, et al. Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change. Stem Cell Res Ther 2021; 12:1-11.
58. Thompson MA, Shaffer L, Larson DA, et al. Subcutaneous anti-inflammatory therapies to prevent burn progression in a swine model of contact burn injury. Milit Med 2024; 189(7-8):1423-31.
59. Ding J, Pan Y, Raj S, et al. Characteristics of serum exosomes after burn Injury and dermal fibroblast regulation by exosomes in vitro. Cells 2023; 12(13):1738.
60. Schulman CI, Namias N, Pizano L, et al. The effect of mesenchymal stem cells improves the healing of burn wounds: a phase 1 dose-escalation clinical trial. Scars Burns Heal 2022; 8:20595131211070783.
61. Kolios G, Paspaliaris V. Mesenchyme stem cell-derived conditioned medium as a potential therapeutic tool in idiopathic pulmonary fibrosis. Biomed 2022; 10(9):2298.
62. Garg S, Garg A, Shukla A, et al. A review on Nano-therapeutic drug delivery carriers for effective wound treatment strategies. Asian J Pharm Pharmacol 2018; 4(2):90-101.
63. Goncalves S, Bas E, Goldstein BJ, et al. Effects of cell-based therapy for treating tympanic membrane perforations in mice. Otolaryngology–Head Neck Surg 2016; 154(6):1106-14.
64. Dong Y, Cui M, Qu J, et al. Conformable hyaluronic acid hydrogel delivers adipose-derived stem cells and promotes regeneration of burn injury. Acta biomaterialia 2020; 108:56-66.
65. Pelizzo G, Avanzini MA, Icaro Cornaglia A, et al. Extracellular vesicles derived from mesenchymal cells: perspective treatment for cutaneous wound healing in pediatrics. Regen Med 2018; 13(4):385-94.
66. He H, Huang W, Zhang S, et al. Microneedle Patch for Transdermal Sequential Delivery of KGF‐2 and aFGF to Enhance Burn Wound Therapy. Small 2024; 20(34):2307485.
67. Shimizu Y, Ntege EH, Inoue Y, et al. Optimizing mesenchymal stem cell extracellular vesicles for chronic wound healing: Bioengineering, standardization, and safety. Reg Ther 2024; 26:260-74.
68. Perez-Patiño C, Barranco I, Li J, et al. Cryopreservation differentially alters the proteome of epididymal and ejaculated pig spermatozoa. Int J Mol Sci 2019; 20(7):1791.
69. Rolandsson Enes S, Andersson Sjöland A, Skog I, et al. MSC from fetal and adult lungs possess lung-specific properties compared to bone marrow-derived MSC. Sci Rep 2016; 6(1):29160.
70. Raposio E, Bertozzi N. How to isolate a ready-to-use adipose-derived stem cells pellet for clinical application. Eur Rev Med Pharmacol Sci 2017; 21(18).
71. Deng X, Zhang S, Qing Q, et al. Distinct biological characteristics of mesenchymal stem cells separated from different components of human placenta. Biochem Biophys Rep 2024; 39:101739.
72. Deng S, Zeng Y, Wu L, et al. The regulatory roles of VEGF‐Notch signaling pathway on aplastic anemia with kidney deficiency and blood stasis. J Cellular Biochem 2019; 120(2):2078-89.
73. Guo H, Li B, Wang W, et al. Mesenchymal stem cells overexpressing IL-35: a novel immunosuppressive strategy and therapeutic target for inducing transplant tolerance. Stem Cell Res Ther 2018; 9:1-8.
74. Cui Z, Li Y, Qin Y, et al. Polymyxin B-targeted liposomal photosensitizer cures MDR A. baumannii burn infections and accelerates wound healing via M1/M2 macrophage polarization. J Cont Release 2024; 366:297-311.
75. Irfan F, Jameel F, Khan I, et al. Role of quercetin and rutin in enhancing the therapeutic potential of mesenchymal stem cells for cold induced burn wound. Reg Ther 2022; 21:225-38.
76. Shin JM, Gwak JW, Kamarajan P, et al. Biomedical applications of nisin. J appl Microbiol 2016; 120(6):1449-65.
77. Solanki R, Makwana N, Kumar R, et al. Nanomedicines as a cutting-edge solution to combat antimicrobial resistance. RSC Adv 2024; 14(45):33568-86.
78. Zhang H, Mi Z, Wang J, et al. D-histidine combated biofilm formation and enhanced the effect of amikacin against Pseudomonas aeruginosa in vitro. Arch Microbiol 2024; 206(4):148.
79. Sanapalli BKR, Yele V, Singh MK, et al. Human beta defensin-2 loaded PLGA nanoparticles impregnated in collagen-chitosan composite scaffold for the management of diabetic wounds. Biomed Pharmacother 2023; 161:114540.
80. Yu J, Zhang Y, Kahkoska AR, et al. Bioresponsive transcutaneous patches. Curr Opinion Biotechnol 2017; 48:28-32.
81. Lin YW, Chen K, Wang J, et al. A proof-of-concept study of the efficacy of systemically administered polymyxins in mouse burn wound infection caused by multidrug-resistant Gram-negative pathogens. Antimicrob Agents Chemother 2018; 62(5):10.1128/aac. 02527-17.
82. Subramani T, Saravanan H, David H, et al. Bioorganic compounds in quorum sensing disruption: strategies, Mechanisms, and future prospects. Bioorganic Chem 2025:108192.
83. Hu X, Liu L, Wang Y, et al. Human umbilical cord‐derived mesenchymal stem cells alleviate acute lung injury caused by severe burn via secreting TSG‐6 and inhibiting inflammatory response. Stem Cells Int 2022; 2022(1):8661689.
84. Wan J, Wang L, Huang Y, et al. Using GRGDSPC peptides to improve re‐endothelialization of decellularized pancreatic scaffolds. Artificial Organs 2020; 44(4):E172-E80.
85. Chen L, Gu Q, Li P, et al. Purification and characterization of Plantaricin ZJ316, a novel bacteriocin against Listeria monocytogenes from Lactobacillus plantarum ZJ316. J Food Prot 2018; 81(12):1929-35.
86. Sawadkar P, Mohanakrishnan J, Rajasekar P, et al. A synergistic relationship between polycaprolactone and natural polymers enhances the physical properties and biological activity of scaffolds. ACS appl Mat Interfaces 2020; 12(12):13587-97.
87. Heredia-Juesas J, Thatcher JE, Lu Y, et al., editors. Non-invasive optical imaging techniques for burn-injured tissue detection for debridement surgery. 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC); 2016: IEEE.
88. Vipin C, Kumar GV. Exosome laden sprayable thermo-sensitive polysaccharide-based hydrogel for enhanced burn wound healing. International J Bio Macromol 2025; 290:138712.
89. Esfandiary R, Saeedi P, Saffarian P, et al. Activated mesenchymal stem cells increase drug susceptibility of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Folia Microbiologica 2024; 69(1):145-54.
90. Roque‐Borda CA, Primo LMDG, Medina‐Alarcón KP, et al. Antimicrobial peptides: a promising alternative to conventional antimicrobials for combating polymicrobial biofilms. Adv Sci 2025; 12(1):2410893.
91. Fan W, Tang Y, Liu Y, et al. ROS-responsive nanoparticles for bioimaging and treating acute lung injury by releasing dexamethasone and improving alveolar macrophage homeostasis. J Nanobiotechnol 2024; 22(1):729.
92. Zhao Y, De Los Santos FG, Wu Z, et al. An ST2‐dependent role of bone marrow‐derived group 2 innate lymphoid cells in pulmonary fibrosis. J Path 2018; 245(4):399-409.
93. Guo C, Liu X, Qiu K, et al. MALAT1 knockdown inhibits the proliferation, migration, and collagen deposition of human hypertrophic scar fibroblasts via targeting miR-29a-3p/Smurf2 axis. Clin Cos Inves Dermatology 2024:1387-404.
94. Murphy KC, Whitehead J, Zhou D, et al. Engineering fibrin hydrogels to promote the wound healing potential of mesenchymal stem cell spheroids. Acta biomaterialia 2017; 64:176-86.
95. Yang Y, Lee EH, Yang Z. Hypoxia-conditioned mesenchymal stem cells in tissue regeneration application. Tissue Eng 2022; 28(5):966-77.
96. Tang XL, Nasr M, Zheng S, et al. Bone marrow and Wharton’s jelly mesenchymal stromal cells are ineffective for myocardial repair in an immunodeficient rat model of chronic ischemic cardiomyopathy. Stem Cell Rev Rep 2023; 19(7):2429-46.
97. Gorman E, Millar J, McAuley D, et al. Mesenchymal stromal cells for acute respiratory distress syndrome (ARDS), sepsis, and COVID-19 infection: optimizing the therapeutic potential. Expert Rev Resp Med 2021; 15(3):301-24.
98. George B, Suchithra T, Bhatia N. Burn injury induces elevated inflammatory traffic: the role of NF-κB. Inflammation Res 2021; 70(1):51-65.
99. Tageldin A, Omolo CA, Nyandoro VO, et al. Engineering dynamic covalent bond-based nanosystems for delivery of antimicrobials against bacterial infections. J Cont Release 2024; 371:237-57.
100. Chua JKE, Lim J, Foong LH, et al. Mesenchymal stem cell-derived extracellular vesicles: Progress and remaining hurdles in developing regulatory compliant quality control assays. Cell Bio Trans Med, 2022; 17:191-211.
2. Wang Y, Beekman J, Hew J, et al. Burn injury: challenges and advances in burn wound healing, infection, pain and scarring. Adv Drug Del Rev 2018; 123:3-17.
3. Brandenburg KS, Weaver AJ, Karna SR, et al. The impact of simultaneous inoculation of Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans on rodent burn wounds. Burns 2021; 47(8):1818-32.
4. Kopecki Z. Development of next-generation antimicrobial hydrogel dressing to combat burn wound infection. Biosci Rep 2021; 41(2):BSR20203404.
5. Wu S, Sun S, Fu W, et al. The role and prospects of mesenchymal stem cells in skin repair and regeneration. Biomed 2024; 12(4):743.
6. Yang X, Yang R, Chen M, et al. KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats. BMJ Open Diabetes Res Care 2020; 8(1).
7. Liu Z, Yang J, Chen Y, et al. P311 facilitates the angiogenesis and wound healing function of MSCs by increasing VEGF production. Front Immunol 2022; 13:821932.
8. Sousa AB, Águas AP, Barbosa MA, et al. Immunomodulatory biomaterial-based wound dressings advance the healing of chronic wounds via regulating macrophage behavior. Regen Biomat 2022;9:rbac065.
9. Wang M, Xu X, Lei X, et al. Mesenchymal stem cell-based therapy for burn wound healing. Burn Trauma 2021; 9:tkab002.
10. Urashima A, Sanou A, Yen H, et al. Enterohaemorrhagic Escherichia coli produces outer membrane vesicles as an active defence system against antimicrobial peptide LL‐37. Cell Microbiol 2017; 19(11):e12758.
11. Zheng J, Liu X, Xiong Y, et al. AMXT-1501 targets membrane phospholipids against Gram-positive and-negative multidrug-resistant bacteria. Emerg Microbe Infec 2024; 13(1):2321981.
12. Bitterlich LM, Tunstead C, Hogan AE, et al. Mesenchymal stromal cells can block palmitate training of macrophages via cyclooxygenase-2 and interleukin-1 receptor antagonist. Cytother 2025; 27(2):169-80.
13. Zheng G, Ge M, Qiu G, et al. Mesenchymal stromal cells affect disease outcomes via macrophage polarization. Stem Cell Int 2015; 2015(1):989473.
14. Elshamy AA, Kamal SK, Mahmoud MT, et al. Recent insights on phage therapy against multidrug-resistant Acinetobacter baumannii. AMB Express 2025; 15(1):1-16.
15. Long X, Yuan Q, Tian R, et al. Efficient healing of diabetic wounds by MSC-EV-7A composite hydrogel via suppression of inflammation and enhancement of angiogenesis. Biomat Sci 2024; 12(7):1750-60.
16. Česnik AB, Švajger U. The issue of heterogeneity of MSC-based advanced therapy medicinal products–a review. Front Cell Dev Bio 2024; 12:1400347.
17. Liu J, Xu Z, Yu J, et al. MiR-146a-5p engineered hucMSC-derived extracellular vesicles attenuate dermatophagoides farinae-induced allergic airway epithelial cell inflammation. Front Immunol 2024; 15:1443166.
18. Iwatake M, Nagamura-Inoue T, Doi R, et al. Designer umbilical cord-stem cells induce alveolar wall regeneration in pulmonary disease models. Front Immunol 2024; 15:1384718.
19. Bártolo I, Reis RL, Marques AP, et al. Keratinocyte growth factor-based strategies for wound re-epithelialization. Tissue Eng 2022; 28(3):665-76.
20. Stewart AN, Matyas JJ, Welchko RM, et al. SDF-1 overexpression by mesenchymal stem cells enhances GAP-43-positive axonal growth following spinal cord injury. Restor Neurol Neurosci 2017; 35(4):395-411.
21. Wu Q, Xu WD, Huang AF. Role of angiopoietin-2 in inflammatory autoimmune diseases: A comprehensive review. Int Immunopharmacol 2020; 80:106223.
22. Slautin V, Konyshev K, Gavrilov I, et al. Fucoxanthin enhances the antifibrotic potential of placenta-derived mesenchymal stem cells in a CCl4-induced mouse model of liver. Curr Stem Cell Res Ther 2024; 19(11):1484-96.
23. Xie C, Mondal DK, Ulas M, et al. Oncosuppressive roles of decorin through regulation of multiple receptors and diverse signaling pathways. Am J Physiology 2022; 322(3):C554-C66.
24. Fang S, Xu C, Zhang Y, et al. Umbilical cord-derived mesenchymal stem cell-derived exosomal microRNAs suppress myofibroblast differentiation by inhibiting the transforming growth factor-β/SMAD2 pathway during wound healing. Stem Cells Trans Med. 2016; 5(10):1425-39.
25. Manzoor T, Farooq N, Sharma A, et al. Exosomes in nanomedicine: a promising cell-free therapeutic intervention in burn wounds. Stem Cell Res Ther 2024; 15(1):355.
26. Kuang L, Zhang C, Li B, et al. Human keratinocyte-derived exosomal MALAT1 promotes diabetic wound healing by upregulating MFGE8 via microRNA-1914-3p. Int J Nanomed 2023:949-70.
27. Rangatchew F, Vester-Glowinski P, Rasmussen BS, et al. Mesenchymal stem cell therapy of acute thermal burns: a systematic review of the effect on inflammation and wound healing. Burns 2021; 47(2):270-94.
28. Mirshekar M, Afkhami H, Razavi S, et al. Potential antibacterial activity and healing effect of topical administration of bone marrow and adipose mesenchymal stem cells encapsulated in collagen-fibrin hydrogel scaffold on full-thickness burn wound infection caused by Pseudomonas aeruginosa. Burns 2023; 49(8):1944-57.
29. Smolinska V, Harsanyi S, Bohac M, et al. Exploring the three-dimensional frontier: advancements in MSC spheroids and their implications for breast cancer and personalized regenerative therapies. Biomed 2023; 12(1):52.
30. da Silva KN, Marim FM, Rocha GV, et al. Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infection. Stem Cell Res Ther 2025; 16(1):15.
31. Enayati S, Halabian R, Saffarian P, et al. Nisin-preconditioned mesenchymal stem cells combatting nosocomial Pseudomonas infections. Regen Ther 2024; 26:161-9.
32. Choudhury S, Madhu Krishna M, Sen D, et al. 3D Porous Polymer Scaffold-Conjugated KGF-Mimetic Peptide Promotes Functional Skin Regeneration in Chronic Diabetic Wounds. ACS Appl Mat Interfaces 2024; 16(29):37418-34.
33. Chouhan D, Lohe TU, Thatikonda N, et al. Silkworm silk scaffolds functionalized with recombinant spider silk containing a fibronectin motif promotes healing of full-thickness burn wounds. ACS Biomat Sci Eng 2019; 5(9):4634-45.
34. Saheli M, Bayat M, Ganji R, et al. Human mesenchymal stem cells-conditioned medium improves diabetic wound healing mainly through modulating fibroblast behaviors. Arch Dermatol Res 2020; 312(5):325-36.
35. Palmieri TL. Emerging therapies for full-thickness skin regeneration. J Burn Care Res 2023; 44:S65-S7.
36. Li CY, Wu XY, Tong JB, et al. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Res Ther 2015; 6:1-13.
37. Redondo-Castro E, Cunningham CJ, Miller J, et al. Changes in the secretome of tri-dimensional spheroid-cultured human mesenchymal stem cells in vitro by interleukin-1 priming. Stem cell Res Ther 2018; 9:1-11.
38. Fu Y, Li J, Zhang Z, et al. Umbilical cord mesenchymal stem cell‐derived exosomes alleviate collagen‐induced arthritis by balancing the population of Th17 and regulatory T cells. FEBS lett 2022; 596(20):2668-77.
39. De Servi B, Orlandini A, Caviola E, et al. Amino acid and hyaluronic acid mixtures differentially regulate extra cellular matrix genes in cultured human fibroblasts. J Biological Reg Homeos Agents 2018; 32(3):517-27.
40. Chen H, Zhao H. Resveratrol enhances the efficacy of combined BM-MSCs therapy for rat spinal cord injury via modulation of the Sirt-1/NF-κB signaling pathway. Neurochem Res 2025; 50(1):12.
41. Putra I, Shen X, Anwar KN, et al. Preclinical evaluation of the safety and efficacy of cryopreserved bone marrow mesenchymal stromal cells for corneal repair. Trans Vision Sci Technol 2021; 10(10):3-.
42. Xu Y, Wang XS, Zhou XL, et al. Mesenchymal stem cell therapy for liver fibrosis need “partner”: Results based on a meta-analysis of preclinical studies. World J Gastroenterol 2024; 30(32):3766.
43. Hermeto LC, DeRossi R, Oliveira RJ, et al. The efficacy of topical insulin application on rat model with burn wounds treated with adipose-derived stem cells. Int J Burns Trauma 2020; 10(6):296.
44. Pyun DG, Choi HJ, Yoon HS, et al. Polyurethane foam containing rhEGF as a dressing material for healing diabetic wounds: synthesis, characterization, in vitro and in vivo studies. Colloids Surfaces 2015; 135:699-706.
45. Incontri Abraham D, Gonzales M, Ibarra A, et al. Stand alone or join forces? Stem cell therapy for stroke. Expert Opinion Bio Ther 2019; 19(1):25-33.
46. Madrigal M, Fernández PL, Lleonart R, et al. Comparison of cost and potency of human mesenchymal stromal cell conditioned medium derived from 2-and 3-dimensional cultures. Bioeng 2023; 10(8):930.
47. Zahorec P, Sarkozyova N, Ferancikova N, et al. Autologous mesenchymal stem cells application in post-burn scars treatment: a preliminary study. Cell Tissue Banking 2021; 22:39-46.
48. Kumar A, Ramesh S, Kumar V, et al. Human second-trimester fetal liver-derived mesenchymal stromal cells are more effective than adult bone marrow MSCs for their superior growth kinetics, immunomodulatory, and osteogenic potential. Tissue Cell 2025; 95:102859.
49. Aslam S, Khan I, Jameel F, et al. Umbilical cord-derived mesenchymal stem cells preconditioned with isorhamnetin: potential therapy for burn wounds. World J Stem Cells 2020; 12(12):1652.
50. Frescaline N, Duchesne C, Favier M, et al. Physical plasma therapy accelerates wound re‐epithelialisation and enhances extracellular matrix formation in cutaneous skin grafts. J Path 2020; 252(4):451-64.
51. Rady D, Abbass MM, El-Rashidy AA, et al. Mesenchymal stem/progenitor cells: the prospect of human clinical translation. Stem Cells Int 2020; 2020(1):8837654.
52. Rolland TJ, Zahra S, Cucinotta D, et al. Mesenchymal stem cell-derived extracellular vesicles mitigate immune cell activation in an in vitro model of post-resuscitation inflammation. bioRxiv 2025; 13.637856.
53. Zhang J, Li LB, Qiu Z, et al. Intravenous injections of human mesenchymal stromal cells modulated the redox state in a rat model of radiation myelopathy. Evid Compl Alt Med. 2015; 2015(1):432369.
54. O'Rourke B, Nguyen S, Tilles AW, et al. Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application. Stem Cells Trans Med 2021; 10(6):883-94.
55. Schriner JB, Triolo F, Gill BS, et al. Low molecular weight heparin decreases pro-coagulant activity in clinical MSC products. Cytotherapy 2024; 26(2):194-200.
56. Arshad T, Mundrathi V, Perez VE, et al. Topical probiotic hydrogels for burn wound healing. Gels 2024; 10(9):545.
57. Eylert G, Dolp R, Parousis A, et al. Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change. Stem Cell Res Ther 2021; 12:1-11.
58. Thompson MA, Shaffer L, Larson DA, et al. Subcutaneous anti-inflammatory therapies to prevent burn progression in a swine model of contact burn injury. Milit Med 2024; 189(7-8):1423-31.
59. Ding J, Pan Y, Raj S, et al. Characteristics of serum exosomes after burn Injury and dermal fibroblast regulation by exosomes in vitro. Cells 2023; 12(13):1738.
60. Schulman CI, Namias N, Pizano L, et al. The effect of mesenchymal stem cells improves the healing of burn wounds: a phase 1 dose-escalation clinical trial. Scars Burns Heal 2022; 8:20595131211070783.
61. Kolios G, Paspaliaris V. Mesenchyme stem cell-derived conditioned medium as a potential therapeutic tool in idiopathic pulmonary fibrosis. Biomed 2022; 10(9):2298.
62. Garg S, Garg A, Shukla A, et al. A review on Nano-therapeutic drug delivery carriers for effective wound treatment strategies. Asian J Pharm Pharmacol 2018; 4(2):90-101.
63. Goncalves S, Bas E, Goldstein BJ, et al. Effects of cell-based therapy for treating tympanic membrane perforations in mice. Otolaryngology–Head Neck Surg 2016; 154(6):1106-14.
64. Dong Y, Cui M, Qu J, et al. Conformable hyaluronic acid hydrogel delivers adipose-derived stem cells and promotes regeneration of burn injury. Acta biomaterialia 2020; 108:56-66.
65. Pelizzo G, Avanzini MA, Icaro Cornaglia A, et al. Extracellular vesicles derived from mesenchymal cells: perspective treatment for cutaneous wound healing in pediatrics. Regen Med 2018; 13(4):385-94.
66. He H, Huang W, Zhang S, et al. Microneedle Patch for Transdermal Sequential Delivery of KGF‐2 and aFGF to Enhance Burn Wound Therapy. Small 2024; 20(34):2307485.
67. Shimizu Y, Ntege EH, Inoue Y, et al. Optimizing mesenchymal stem cell extracellular vesicles for chronic wound healing: Bioengineering, standardization, and safety. Reg Ther 2024; 26:260-74.
68. Perez-Patiño C, Barranco I, Li J, et al. Cryopreservation differentially alters the proteome of epididymal and ejaculated pig spermatozoa. Int J Mol Sci 2019; 20(7):1791.
69. Rolandsson Enes S, Andersson Sjöland A, Skog I, et al. MSC from fetal and adult lungs possess lung-specific properties compared to bone marrow-derived MSC. Sci Rep 2016; 6(1):29160.
70. Raposio E, Bertozzi N. How to isolate a ready-to-use adipose-derived stem cells pellet for clinical application. Eur Rev Med Pharmacol Sci 2017; 21(18).
71. Deng X, Zhang S, Qing Q, et al. Distinct biological characteristics of mesenchymal stem cells separated from different components of human placenta. Biochem Biophys Rep 2024; 39:101739.
72. Deng S, Zeng Y, Wu L, et al. The regulatory roles of VEGF‐Notch signaling pathway on aplastic anemia with kidney deficiency and blood stasis. J Cellular Biochem 2019; 120(2):2078-89.
73. Guo H, Li B, Wang W, et al. Mesenchymal stem cells overexpressing IL-35: a novel immunosuppressive strategy and therapeutic target for inducing transplant tolerance. Stem Cell Res Ther 2018; 9:1-8.
74. Cui Z, Li Y, Qin Y, et al. Polymyxin B-targeted liposomal photosensitizer cures MDR A. baumannii burn infections and accelerates wound healing via M1/M2 macrophage polarization. J Cont Release 2024; 366:297-311.
75. Irfan F, Jameel F, Khan I, et al. Role of quercetin and rutin in enhancing the therapeutic potential of mesenchymal stem cells for cold induced burn wound. Reg Ther 2022; 21:225-38.
76. Shin JM, Gwak JW, Kamarajan P, et al. Biomedical applications of nisin. J appl Microbiol 2016; 120(6):1449-65.
77. Solanki R, Makwana N, Kumar R, et al. Nanomedicines as a cutting-edge solution to combat antimicrobial resistance. RSC Adv 2024; 14(45):33568-86.
78. Zhang H, Mi Z, Wang J, et al. D-histidine combated biofilm formation and enhanced the effect of amikacin against Pseudomonas aeruginosa in vitro. Arch Microbiol 2024; 206(4):148.
79. Sanapalli BKR, Yele V, Singh MK, et al. Human beta defensin-2 loaded PLGA nanoparticles impregnated in collagen-chitosan composite scaffold for the management of diabetic wounds. Biomed Pharmacother 2023; 161:114540.
80. Yu J, Zhang Y, Kahkoska AR, et al. Bioresponsive transcutaneous patches. Curr Opinion Biotechnol 2017; 48:28-32.
81. Lin YW, Chen K, Wang J, et al. A proof-of-concept study of the efficacy of systemically administered polymyxins in mouse burn wound infection caused by multidrug-resistant Gram-negative pathogens. Antimicrob Agents Chemother 2018; 62(5):10.1128/aac. 02527-17.
82. Subramani T, Saravanan H, David H, et al. Bioorganic compounds in quorum sensing disruption: strategies, Mechanisms, and future prospects. Bioorganic Chem 2025:108192.
83. Hu X, Liu L, Wang Y, et al. Human umbilical cord‐derived mesenchymal stem cells alleviate acute lung injury caused by severe burn via secreting TSG‐6 and inhibiting inflammatory response. Stem Cells Int 2022; 2022(1):8661689.
84. Wan J, Wang L, Huang Y, et al. Using GRGDSPC peptides to improve re‐endothelialization of decellularized pancreatic scaffolds. Artificial Organs 2020; 44(4):E172-E80.
85. Chen L, Gu Q, Li P, et al. Purification and characterization of Plantaricin ZJ316, a novel bacteriocin against Listeria monocytogenes from Lactobacillus plantarum ZJ316. J Food Prot 2018; 81(12):1929-35.
86. Sawadkar P, Mohanakrishnan J, Rajasekar P, et al. A synergistic relationship between polycaprolactone and natural polymers enhances the physical properties and biological activity of scaffolds. ACS appl Mat Interfaces 2020; 12(12):13587-97.
87. Heredia-Juesas J, Thatcher JE, Lu Y, et al., editors. Non-invasive optical imaging techniques for burn-injured tissue detection for debridement surgery. 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC); 2016: IEEE.
88. Vipin C, Kumar GV. Exosome laden sprayable thermo-sensitive polysaccharide-based hydrogel for enhanced burn wound healing. International J Bio Macromol 2025; 290:138712.
89. Esfandiary R, Saeedi P, Saffarian P, et al. Activated mesenchymal stem cells increase drug susceptibility of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Folia Microbiologica 2024; 69(1):145-54.
90. Roque‐Borda CA, Primo LMDG, Medina‐Alarcón KP, et al. Antimicrobial peptides: a promising alternative to conventional antimicrobials for combating polymicrobial biofilms. Adv Sci 2025; 12(1):2410893.
91. Fan W, Tang Y, Liu Y, et al. ROS-responsive nanoparticles for bioimaging and treating acute lung injury by releasing dexamethasone and improving alveolar macrophage homeostasis. J Nanobiotechnol 2024; 22(1):729.
92. Zhao Y, De Los Santos FG, Wu Z, et al. An ST2‐dependent role of bone marrow‐derived group 2 innate lymphoid cells in pulmonary fibrosis. J Path 2018; 245(4):399-409.
93. Guo C, Liu X, Qiu K, et al. MALAT1 knockdown inhibits the proliferation, migration, and collagen deposition of human hypertrophic scar fibroblasts via targeting miR-29a-3p/Smurf2 axis. Clin Cos Inves Dermatology 2024:1387-404.
94. Murphy KC, Whitehead J, Zhou D, et al. Engineering fibrin hydrogels to promote the wound healing potential of mesenchymal stem cell spheroids. Acta biomaterialia 2017; 64:176-86.
95. Yang Y, Lee EH, Yang Z. Hypoxia-conditioned mesenchymal stem cells in tissue regeneration application. Tissue Eng 2022; 28(5):966-77.
96. Tang XL, Nasr M, Zheng S, et al. Bone marrow and Wharton’s jelly mesenchymal stromal cells are ineffective for myocardial repair in an immunodeficient rat model of chronic ischemic cardiomyopathy. Stem Cell Rev Rep 2023; 19(7):2429-46.
97. Gorman E, Millar J, McAuley D, et al. Mesenchymal stromal cells for acute respiratory distress syndrome (ARDS), sepsis, and COVID-19 infection: optimizing the therapeutic potential. Expert Rev Resp Med 2021; 15(3):301-24.
98. George B, Suchithra T, Bhatia N. Burn injury induces elevated inflammatory traffic: the role of NF-κB. Inflammation Res 2021; 70(1):51-65.
99. Tageldin A, Omolo CA, Nyandoro VO, et al. Engineering dynamic covalent bond-based nanosystems for delivery of antimicrobials against bacterial infections. J Cont Release 2024; 371:237-57.
100. Chua JKE, Lim J, Foong LH, et al. Mesenchymal stem cell-derived extracellular vesicles: Progress and remaining hurdles in developing regulatory compliant quality control assays. Cell Bio Trans Med, 2022; 17:191-211.
| Files | ||
| Issue | Vol 13 No 3 (2025) | |
| Section | Review Articles | |
| DOI | https://doi.org/10.18502/jmb.v13i3.19517 | |
| Keywords | ||
| Mesenchymal Stem Cells Antimicrobial Burn Wound Healing | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Poureslamfar B, Yadegari S, Rahman Mufazzil K, Karimi M, Misaii B, Tehrani Niya F, Yekani R, Esmaeili Dahaj F, Abesi A, Mohammadzadeh M. Beyond Regeneration: Mesenchymal Stem Cells as Antimicrobial Agents in Burn Wound Healing. J Med Bacteriol. 2025;13(3):146-168.
