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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

The Effect of Mesenchymal Stem Cells on the Wound Infection

Author(s): Mansoor Khaledi, Bita Zandi and Zeinab Mohsenipour*

Volume 19, Issue 8, 2024

Published on: 05 October, 2023

Page: [1084 - 1092] Pages: 9

DOI: 10.2174/011574888X252482230926104342

Price: $65

Abstract

Wound infection often requires a long period of care and an onerous treatment process. Also, the rich environment makes the wound an ideal niche for microbial growth. Stable structures, like biofilm, and drug-resistant strains cause a delay in the healing process, which has become one of the important challenges in wound treatment. Many studies have focused on alternative methods to deal the wound infections. One of the novel and highly potential ways is mesenchymal stromal cells (MSCs). MSCs are mesoderm-derived pluripotent adult stem cells with the capacity for self-renewal, multidirectional differentiation, and immunological control. Also, MSCs have anti-inflammatory and antiapoptotic effects. MScs, as pluripotent stromal cells, differentiate into many mature cells. Also, MSCs produce antimicrobial compounds, such as antimicrobial peptides (AMP), as well as secrete immune modulators, which are two basic features considered in wound healing. Despite the advantages, preserving the structure and activity of MSCs is considered one of the most important points in the treatment. MSCs’ antimicrobial effects on microorganisms involved in wound infection have been confirmed in various studies. In this review, we aimed to discuss the antimicrobial and therapeutic applications of MSCs in the infected wound healing processes.

Keywords: Antimicrobial peptides, mesenchymal stromal cells (MSCs), wound healing, antimicrobial compounds, immune modulators.

Graphical Abstract
[1]
Motelica L, Popescu A, Răzvan A-G, Oprea O, Truşcă R-D, Vasile B-S, et al. Facile use of ZnO nanopowders to protect old manual paper documents. Materials 2020; 13(23): 5452.
[http://dx.doi.org/10.3390/ma13235452]
[2]
Değim Z, Çelebi N, Alemdaroğlu C, Deveci M, Öztürk S, Özoğul C. Evaluation of chitosan gel containing liposome-loaded epidermal growth factor on burn wound healing. Int Wound J 2011; 8(4): 343-54.
[http://dx.doi.org/10.1111/j.1742-481X.2011.00795.x] [PMID: 21486392]
[3]
Gushiken LFS, Beserra FP, Bastos JK, Jackson CJ, Pellizzon CH. Cutaneous wound healing: An update from physiopathology to current therapies. Life 2021; 11(7): 665.
[http://dx.doi.org/10.3390/life11070665] [PMID: 34357037]
[4]
Kadam S, Shai S, Shahane A, Kaushik KS. Recent advances in non-conventional antimicrobial approaches for chronic wound biofilms: Have we found the ‘chink in the armor’? Biomedicines 2019; 7(2): 35.
[http://dx.doi.org/10.3390/biomedicines7020035] [PMID: 31052335]
[5]
Tillotson GS, Theriault N. New and alternative approaches to tackling antibiotic resistance. F1000Prime Rep 2013; 5: 51.
[http://dx.doi.org/10.12703/P5-51] [PMID: 24381727]
[6]
Strudwick XL, Whittle JD, Cowin AJ, Smith LE. Plasma-functionalised dressings for enhanced wound healing. Int J Mol Sci 2023; 24(1): 797.
[http://dx.doi.org/10.3390/ijms24010797] [PMID: 36614239]
[7]
Zhao X, Zhang W, Fan J, Chen X, Wang X. Application of mesenchymal stem cell exosomes in the treatment of skin wounds. Smart Mater Med 2023; 4: 578-89.
[http://dx.doi.org/10.1016/j.smaim.2023.04.006]
[8]
Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284(5411): 143-7.
[http://dx.doi.org/10.1126/science.284.5411.143] [PMID: 10102814]
[9]
Kim N, Cho SG. Clinical applications of mesenchymal stem cells. Korean J Intern Med (Korean Assoc Intern Med) 2013; 28(4): 387-402.
[http://dx.doi.org/10.3904/kjim.2013.28.4.387] [PMID: 23864795]
[10]
Belokhvostova D, Berzanskyte I, Cujba A-M, Jowett G, Marshall L, Prueller J, et al. Homeostasis, regeneration and tumour formation in the mammalian epidermis. Int J Dev Biol 2018; 62((6-7-8)): 571-82.
[http://dx.doi.org/10.1387/ijdb.170341fw]
[11]
Nair HKR, Ahmad NW, Lee HL, et al. Hirudotherapy in wound healing. Int J Low Extrem Wounds 2022; 21(4): 425-31.
[http://dx.doi.org/10.1177/1534734620948299] [PMID: 32815407]
[12]
Arthur A, Zannettino A, Gronthos S. The therapeutic applications of multipotential mesenchymal/stromal stem cells in skeletal tissue repair. J Cell Physiol 2009; 218(2): 237-45.
[http://dx.doi.org/10.1002/jcp.21592] [PMID: 18792913]
[13]
Waghray M, Yalamanchili M, Dziubinski M, et al. GM-CSF mediates mesenchymal-epithelial cross-talk in pancreatic cancer. Cancer Discov 2016; 6(8): 886-99.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0947] [PMID: 27184426]
[14]
Jiang D, Muschhammer J, Qi Y, et al. Suppression of neutrophil-mediated tissue damage-a novel skill of mesenchymal stem cells. Stem Cells 2016; 34(9): 2393-406.
[http://dx.doi.org/10.1002/stem.2417] [PMID: 27299700]
[15]
Petri RM, Hackel A, Hahnel K, et al. Activated tissue-resident mesenchymal stromal cells regulate natural killer cell immune and tissue-regenerative function. Stem Cell Reports 2017; 9(3): 985-98.
[http://dx.doi.org/10.1016/j.stemcr.2017.06.020] [PMID: 28781075]
[16]
Harrell CR, Jovicic N, Djonov V, Arsenijevic N, Volarevic V. Mesenchymal stem cell-derived exosomes and other extracellular vesicles as new remedies in the therapy of inflammatory diseases. Cells 2019; 8(12): 1605.
[http://dx.doi.org/10.3390/cells8121605] [PMID: 31835680]
[17]
Bevan D, Gherardi E, Fan TP, Edwards D, Warn R. Diverse and potent activities of HGF/SF in skin wound repair. J Pathol 2004; 203(3): 831-8.
[http://dx.doi.org/10.1002/path.1578] [PMID: 15221943]
[18]
Li H, Fu X, Ouyang Y, Cai C, Wang J, Sun T. Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages. Cell Tissue Res 2006; 326(3): 725-36.
[http://dx.doi.org/10.1007/s00441-006-0270-9] [PMID: 16906419]
[19]
Shittu AO, Kolawole DO, Oyedepo EAR. A study of wound infections in two health institutions in Ile-Ife, Nigeria. Afr J Biomed Res 2010; 5(3): 97-102.
[http://dx.doi.org/10.4314/ajbr.v5i3.53994]
[20]
Brackman G, De Meyer L, Nelis HJ, Coenye T. Biofilm inhibitory and eradicating activity of wound care products against Staphylococcus aureus and Staphylococcus epidermidis biofilms in an in vitro chronic wound model. J Appl Microbiol 2013; 114(6): 1833-42.
[http://dx.doi.org/10.1111/jam.12191] [PMID: 23490006]
[21]
Ding Y, Li W, Zhang F, et al. Electrospun fibrous architectures for drug delivery, tissue engineering and cancer therapy. Adv Funct Mater 2019; 29(2): 1802852.
[http://dx.doi.org/10.1002/adfm.201802852]
[22]
Grinnell F, Zhu M. Fibronectin degradation in chronic wounds depends on the relative levels of elastase, alpha1-proteinase inhibitor, and alpha2-macroglobulin. J Invest Dermatol 1996; 106(2): 335-41.
[http://dx.doi.org/10.1111/1523-1747.ep12342990] [PMID: 8601737]
[23]
D’Arpa P, Leung KP. Toll-like receptor signaling in burn wound healing and scarring. Adv Wound Care 2017; 6(10): 330-43.
[http://dx.doi.org/10.1089/wound.2017.0733] [PMID: 29062590]
[24]
Rani M, Nicholson SE, Zhang Q, Schwacha MG. Damage-associated molecular patterns (DAMPs) released after burn are associated with inflammation and monocyte activation. Burns 2017; 43(2): 297-303.
[http://dx.doi.org/10.1016/j.burns.2016.10.001] [PMID: 28341255]
[25]
Dowd SE, Wolcott RD, Sun Y, McKeehan T, Smith E, Rhoads D. Polymicrobial nature of chronic diabetic foot ulcer biofilm infections determined using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP). PLoS One 2008; 3(10): e3326.
[http://dx.doi.org/10.1371/journal.pone.0003326] [PMID: 18833331]
[26]
Roy S, Elgharably H, Sinha M, et al. Mixed-species biofilm compromises wound healing by disrupting epidermal barrier function. J Pathol 2014; 233(4): 331-43.
[http://dx.doi.org/10.1002/path.4360] [PMID: 24771509]
[27]
Rahim K, Saleha S, Zhu X, Huo L, Basit A, Franco OL. Bacterial contribution in chronicity of wounds. Microb Ecol 2017; 73(3): 710-21.
[http://dx.doi.org/10.1007/s00248-016-0867-9] [PMID: 27742997]
[28]
Walsh EE, Greene L, Kirshner R. Sustained reduction in methicillin-resistant Staphylococcus aureus wound infections after cardiothoracic surgery. Arch Intern Med 2011; 171(1): 68-73.
[PMID: 20837818]
[29]
Lowy FD. Staphylococcus aureus infections. N Engl J Med 1998; 339(8): 520-32.
[http://dx.doi.org/10.1056/NEJM199808203390806] [PMID: 9709046]
[30]
Wen MM, Abdelwahab IA, Aly RG, El-Zahaby SA. Nanophyto-gel against multi-drug resistant pseudomonas aeruginosa burn wound infection. Drug Deliv 2021; 28(1): 463-77.
[http://dx.doi.org/10.1080/10717544.2021.1889720] [PMID: 33620004]
[31]
Slade EA, Thorn RMS, Young AE, Reynolds DM. Real-time detection of volatile metabolites enabling species-level discrimination of bacterial biofilms associated with wound infection. J Appl Microbiol 2022; 132(3): 1558-72.
[http://dx.doi.org/10.1111/jam.15313] [PMID: 34617369]
[32]
Gallo J, Holinka M, Moucha C. Antibacterial surface treatment for orthopaedic implants. Int J Mol Sci 2014; 15(8): 13849-80.
[http://dx.doi.org/10.3390/ijms150813849] [PMID: 25116685]
[33]
Yuan Z, Cheng J, Lan G, Lu F. A cellulose/Konjac glucomannan-based macroporous antibacterial wound dressing with synergistic and complementary effects for accelerated wound healing. Cellulose 2021; 28(9): 5591-609.
[http://dx.doi.org/10.1007/s10570-021-03821-x]
[34]
Bal-Öztürk A, Özkahraman B, Özbaş Z, Yaşayan G, Tamahkar E, Alarçin E. Advancements and future directions in the antibacterial wound dressings – A review. J Biomed Mater Res B Appl Biomater 2021; 109(5): 703-16.
[http://dx.doi.org/10.1002/jbm.b.34736] [PMID: 33047502]
[35]
Wyszogrodzka G, Marszałek B, Gil B, Dorożyński P. Metal-organic frameworks: Mechanisms of antibacterial action and potential applications. Drug Discov Today 2016; 21(6): 1009-18.
[http://dx.doi.org/10.1016/j.drudis.2016.04.009] [PMID: 27091434]
[36]
Harman RM, Yang S, He MK, Van de Walle GR. Antimicrobial peptides secreted by equine mesenchymal stromal cells inhibit the growth of bacteria commonly found in skin wounds. Stem Cell Res Ther 2017; 8(1): 157.
[http://dx.doi.org/10.1186/s13287-017-0610-6] [PMID: 28676123]
[37]
Krasnodembskaya A, Song Y, Fang X, et al. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells 2010; 28(12): 2229-38.
[http://dx.doi.org/10.1002/stem.544] [PMID: 20945332]
[38]
Alcayaga-Miranda F, Cuenca J, Martin A, Contreras L, Figueroa FE, Khoury M. Combination therapy of menstrual derived mesenchymal stem cells and antibiotics ameliorates survival in sepsis. Stem Cell Res Ther 2015; 6(1): 199.
[http://dx.doi.org/10.1186/s13287-015-0192-0] [PMID: 26474552]
[39]
Alcayaga-Miranda F, Cuenca J, Khoury M. Antimicrobial activity of mesenchymal stem cells: Current status and new perspectives of antimicrobial peptide-based therapies. Front Immunol 2017; 8: 339.
[http://dx.doi.org/10.3389/fimmu.2017.00339] [PMID: 28424688]
[40]
Shi M, Yang Q, Monsel A, et al. Preclinical efficacy and clinical safety of clinical grade nebulized allogenic adipose mesenchymal stromal cells derived extracellular vesicles. J Extracell Vesicles 2021; 10(10): e12134.
[http://dx.doi.org/10.1002/jev2.12134] [PMID: 34429860]
[41]
Sutton MT, Fletcher D, Ghosh SK, et al. Antimicrobial properties of mesenchymal stem cells: Therapeutic potential for cystic fibrosis infection, and treatment. Stem Cells Int 2016; 2016: 1-12.
[http://dx.doi.org/10.1155/2016/5303048] [PMID: 26925108]
[42]
Okoli CO, Akah PA, Okoli AS. Potentials of leaves of Aspilia africana (Compositae) in wound care: An experimental evaluation. BMC Complement Altern Med 2007; 7(1): 24.
[http://dx.doi.org/10.1186/1472-6882-7-24] [PMID: 17623087]
[43]
Chow L, Johnson V, Impastato R, Coy J, Strumpf A, Dow S. 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 2020; 9(2): 235-49.
[http://dx.doi.org/10.1002/sctm.19-0092] [PMID: 31702119]
[44]
Jeschke MG, Rehou S, McCann MR, Shahrokhi S. Allogeneic mesenchymal stem cells for treatment of severe burn injury. Stem Cell Res Ther 2019; 10(1): 337.
[http://dx.doi.org/10.1186/s13287-019-1465-9] [PMID: 31752987]
[45]
Wood CR, Al Dhahri D, Al Delfi I, et al. Human adipose tissue-derived mesenchymal stem/stromal cells adhere to and inhibit the growth of Staphylococcus aureus and Pseudomonas aeruginosa. J Med Microbiol 2018; 67(12): 1789-95.
[http://dx.doi.org/10.1099/jmm.0.000861] [PMID: 30351262]
[46]
Guerra AD, Cantu DA, Vecchi JT, Rose WE, Hematti P, Kao WJ. Mesenchymal stromal/stem cell and minocycline-loaded hydrogels inhibit the growth of staphylococcus aureus that evades immunomodulation of blood-derived leukocytes. AAPS J 2015; 17(3): 620-30.
[http://dx.doi.org/10.1208/s12248-015-9728-6] [PMID: 25716147]
[47]
Ren Z, Zheng X, Yang H, et al. Human umbilical-cord mesenchymal stem cells inhibit bacterial growth and alleviate antibiotic resistance in neonatal imipenem-resistant Pseudomonas aeruginosa infection. Innate Immun 2020; 26(3): 215-21.
[http://dx.doi.org/10.1177/1753425919883932] [PMID: 31623477]
[48]
Kudinov VA, Artyushev RI, Zurina IM, et al. Antimicrobial and regenerative effects of placental multipotent mesenchymal stromal cell secretome-based chitosan gel on infected burns in rats. Pharmaceuticals 2021; 14(12): 1263.
[http://dx.doi.org/10.3390/ph14121263] [PMID: 34959663]
[49]
Cortés-Araya Y, Amilon K, Rink BE, et al. Comparison of antibacterial and immunological properties of mesenchymal stem/stromal cells from equine bone marrow, endometrium, and adipose tissue. Stem Cells Dev 2018; 27(21): 1518-25.
[http://dx.doi.org/10.1089/scd.2017.0241] [PMID: 30044182]
[50]
Mot YY, Othman I, Sharifah SH. Synergistic antibacterial effect of co-administering adipose-derived mesenchymal stromal cells and Ophiophagus hannah l-amino acid oxidase in a mouse model of methicillin-resistant Staphylococcus aureus-infected wounds. Stem Cell Res Ther 2017; 8(1): 5.
[http://dx.doi.org/10.1186/s13287-016-0457-2] [PMID: 28114965]
[51]
Moosazadeh Moghaddam M, Eftekhary M, Erfanimanesh S, et al. Comparison of the antibacterial effects of a short cationic peptide and 1% silver bioactive glass against extensively drug-resistant bacteria, Pseudomonas aeruginosa and Acinetobacter baumannii, isolated from burn patients. Amino Acids 2018; 50(11): 1617-28.
[http://dx.doi.org/10.1007/s00726-018-2638-z] [PMID: 30145712]
[52]
Mirshekar M, Afkhami H, Razavi S, Masjedian Jazi F, Darban-Sarokhalil D, Ohadi E, 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.
[http://dx.doi.org/10.1016/j.burns.2023.01.005]
[53]
Ahmadi H, Amini A, Fadaei Fathabady F, et al. Transplantation of photobiomodulation-preconditioned diabetic stem cells accelerates ischemic wound healing in diabetic rats. Stem Cell Res Ther 2020; 11(1): 494.
[http://dx.doi.org/10.1186/s13287-020-01967-2] [PMID: 33239072]
[54]
Fridoni M, Kouhkheil R, Abdollhifar MA, et al. Improvement in infected wound healing in type 1 diabetic rat by the synergistic effect of photobiomodulation therapy and conditioned medium. J Cell Biochem 2019; 120(6): 9906-16.
[http://dx.doi.org/10.1002/jcb.28273] [PMID: 30556154]
[55]
Kouhkheil R, Fridoni M, Piryaei A, et al. The effect of combined pulsed wave low level laser therapy and mesenchymal stem cell conditioned medium on the healing of an infected wound with methicillin resistant Staphylococcal aureus in diabetic rats. J Cell Biochem 2018; 119(7): 5788-97.
[http://dx.doi.org/10.1002/jcb.26759] [PMID: 29574990]
[56]
Huang J, Wu S, Wu M, Zeng Q, Wang X, Wang H. 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. Photodiagn Photodyn Ther 2021; 36: 102480.
[http://dx.doi.org/10.1016/j.pdpdt.2021.102480] [PMID: 34375775]
[57]
Seebach E, Holschbach J, Buchta N, Bitsch RG, Kleinschmidt K, Richter W. Mesenchymal stromal cell implantation for stimulation of long bone healing aggravates Staphylococcus aureus induced osteomyelitis. Acta Biomater 2015; 21: 165-77.
[http://dx.doi.org/10.1016/j.actbio.2015.03.019] [PMID: 25805108]
[58]
Hu H, Wang D, Li L, Yin H, He G, Zhang Y. Role of microRNA-335 carried by bone marrow mesenchymal stem cells-derived extracellular vesicles in bone fracture recovery. Cell Death Dis 2021; 12(2): 156.
[http://dx.doi.org/10.1038/s41419-021-03430-3] [PMID: 33542183]
[59]
Marupanthorn K, Tantrawatpan C, Kheolamai P, Tantikanlayaporn D, Manochantr S. Bone morphogenetic protein-2 enhances the osteogenic differentiation capacity of mesenchymal stromal cells derived from human bone marrow and umbilical cord. Int J Mol Med 2017; 39(3): 654-62.
[http://dx.doi.org/10.3892/ijmm.2017.2872] [PMID: 28204808]
[60]
Granero-Moltó F, Weis JA, Miga MI, et al. Regenerative effects of transplanted mesenchymal stem cells in fracture healing. Stem Cells 2009; 27(8): 1887-98.
[http://dx.doi.org/10.1002/stem.103] [PMID: 19544445]
[61]
Wagner JM, Reinkemeier F, Wallner C, et al. Adipose-derived stromal cells are capable of restoring bone regeneration after post-traumatic osteomyelitis and modulate B-cell response. Stem Cells Transl Med 2019; 8(10): 1084-91.
[http://dx.doi.org/10.1002/sctm.18-0266] [PMID: 31179644]
[62]
Larsen L, Tchanque-Fossuo CN, Gorouhi F, Boudreault D, Nguyen C, Fuentes JJ, et al. Combination therapy of autologous adipose mesenchymal stem cell-enriched, high-density lipoaspirate and topical timolol for healing chronic wounds. J Tissue Eng Regenerat Med 2018; 12: 186-90.
[http://dx.doi.org/10.1002/term.2390]
[63]
Pérez-Díaz MA, Silva-Bermudez P, Jiménez-López B, et al. Silver-pig skin nanocomposites and mesenchymal stem cells: Suitable antibiofilm cellular dressings for wound healing. J Nanobiotechnol 2018; 16(1): 2.
[http://dx.doi.org/10.1186/s12951-017-0331-0] [PMID: 29321021]
[64]
Piatkowski M, Kitala D, Radwan-Pragłowska J, et al. Chitosan/aminoacid hydrogels with antimicrobial and bioactive properties as new scaffolds for human mesenchymal stem cells culture applicable in wound healing. Express Polym Lett 2018; 12(1): 100-12.
[http://dx.doi.org/10.3144/expresspolymlett.2018.8]
[65]
Wang S, Hou Y, Li X, et al. Comparison of exosomes derived from induced pluripotent stem cells and mesenchymal stem cells as therapeutic nanoparticles for treatment of corneal epithelial defects. Aging 2020; 12(19): 19546-62.
[http://dx.doi.org/10.18632/aging.103904] [PMID: 33049719]

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