AccScience Publishing / JCTR / Volume 8 / Issue 4 / DOI: 10.18053/jctres.08.202204.003
REVIEW ARTICLE

Systemic anti-inflammatory effects of mesenchymal stem cells in burn: A systematic review of animal studies

Abdullah S. Eldaly1 * Sarah M. Mashaly2 Eslam Fouda3 Omar S. Emam1 Amro Aglan4 Jumanah Abuasbeh5 Aditya Khurana6 Hiba Hamdar7 Ayman R. Fath6
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1 Division of Plastic Surgery, Mayo Clinic, Jacksonville, Florida
2 Department of Dermatology, El-Menshawy General Hospital, Tanta, Egypt
3 Division of Anesthesia and Perioperative Medicine, Mayo Clinic, Jacksonville, Florida
4 Department of Internal Medicine, Lahey Clinic Beth Israel, Boston, Massachusetts
5 Department of Public Health, University of Arizona, Phoenix, Arizona
6 Department of Internal Medicine, Creighton University Health Education Alliance, Phoenix, Arizona
7 Department of Emergency Medicine, Notre Dame Maritime Hospital, Byblos, Lebanon
Received: 20 February 2022 | Revised: 18 May 2022 | Accepted: 19 May 2022 | Published online: 18 July 2022
© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Background: Despite the advances in burn care, severe burns still impose significant morbidity and mortality. Severe burns are associated with an inflammatory response that ranges from alterations in vital signs to shock, multiorgan failure and death. Mesenchymal stem cells (MSCs) are known for their anti-inflammatory and immunomodulatory effects. Therefore, MSCs were investigated for their potential benefits in modulating burn-induced inflammation and organ damage in several studies.

Aim: We have conducted a systematic review of literature to evaluate the efficacy of MSCs in modulating burn-induced systemic inflammation and organ damage in animal models.

Methods: Four databases were searched: PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Scopus, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) as our basis of organization.

Results: Eight studies were included. Bone marrow derived MSCs (BMMSCs), umbilical cord derived MSCs (UC-MSCs), and UC-MSCs exosomes were used to modulate the burn-induced inflammation. MSCs therapy reduced serum levels of pro-inflammatory cytokines, improved renal fucntion, inhibited tissue damage, and improved survival after burn. Furthermore, MSCs reversed all the burn-induced pathological changes in blood brain barrier (BBB).

Conclusion: MSCs may attenuate the burn-induced inflammation by decreasing serum levels of inflammatory cytokines. However, the effect on anti-inflammatory cytokines is conflicting and mandates more substantial evidence. Furthermore, MSCs reduce tissue inflammation, tissue damage, and apoptosis in the lungs and kidneys. In addition, MSCs reversed the burn-induced pathophysiologic changes in the BBB. The underlying mechanisms of these effects are poorly understood and should be the focus of future stem cell research.

Relevance to patients: Severe burn patients are liable to systemic inflammation due to the release of inflammatory cytokines into the circulation. This inflammatory response has a broad spectrum of severity that ranges from alterations in vital signs to multiorgan failure and death. Despite the advances in burn care, burn-induced inflammation still imposes significant morbidity and mortality. This systematic review evaluates the potential benefits of stem cells in modulating burn-induced systemic inflammation in animal burn models.

Keywords
animal models
burn
exosomes
mesenchymal stem cells
systemic inflammation
Conflict of interest
The authors report no conflict of interest.
References

[1] Przkora R, Barrow RE, Jeschke MG, Suman OE, Celis M, Sanford AP, et al. Body Composition Changes with Time in Pediatric Burn Patients. J Trauma 2006;60:968-71.

[2] Finnerty CC, Herndon DN, Przkora R, Pereira CT, Oliveira HM, Queiroz DM, et al. Cytokine Expression Profile Over Time in Severely Burned Pediatric Patients. Shock 2006;26:13-9.

[3] Jeschke MG, Chinkes DL, Finnerty CC, Kulp G, SumanOE, Norbury WB, et al. Pathophysiologic Response to Severe Burn Injury. Ann Surg 2008;248:387-401.

[4] Jeschke MG, van Baar ME, Choudhry MA, Chung KK, Gibran NS, Logsetty S. Burn iNjury. Nat Rev Dis Primers 2020;6:11.

[5] Toliver-Kinsky T, Kobayashi M, Suzuki F, Sherwood ER. The systemic inflammatory response syndrome. In: Total Burn Care. Amsterdam, Netherlands: Elsevier Inc.; 2018. p. 205-20.e204.

[6] Han Y, Li X, Zhang Y, Han Y, Chang F, Ding J. Mesenchymal Stem Cells for Regenerative Medicine. Cells 2019;8:E886.

[7] Fu X, Liu G, Halim A, Ju Y, Luo Q, Song AG. Mesenchymal Stem Cell Migration and Tissue Repair. Cells 2019;8:E784.

[8] Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, et al. Mesenchymal Stem Cells and Immunomodulation: Current Status and Future Prospects. Cell Death Dis 2016;7:e2062.

[9] Jo H, Brito S, Kwak BM, Park S, Lee MG, Bin BH. Applications of Mesenchymal Stem Cells in Skin Regeneration and Rejuvenation. Int J Mol Sci 2021;22:2410.

[10] Mazini L, Rochette L, Admou B, Amal S, Malka G. Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing. Int J Mol Sci 2020;21:E1306.

[11] Cosenza S, Toupet K, Maumus M, Luz-Crawford P, BlancBrude O, Jorgensen C, et al. Mesenchymal Stem Cellsderived Exosomes are more Immunosuppressive than Microparticles in Inflammatory Arthritis. Theranostics 2018;8:1399-410.

[12] Li JY, Ren KK, Zhang WJ, Xiao L, Wu HY, Liu QY, et al. Human Amniotic Mesenchymal Stem Cells and their Paracrine Factors Promote Wound Healing by Inhibiting Heat Stress-induced Skin Cell Apoptosis and Enhancing their Proliferation Through Activating PI3K/AKT Signaling Pathway. Stem Cell Res Ther 2019;10:247.

[13] Amini-Nik S, Dolp R, Eylert G, Datu AK, Parousis A, Blakeley C, et al. Stem Cells Derived from Burned Skin the Future of Burn Care. EBioMedicine 2018;37:509-20.

[14] Shumakov VI, Onishchenko NA, Rasulov MF, Krasheninnikov ME, Zaidenov VA. Mesenchymal Bone Marrow Stem Cells more Effectively Stimulate Regeneration of Deep Burn Wounds than Embryonic Fibroblasts. Bull Exp Biol Med 2003;136:192-5.

[15] Xue L, Xu YB, Xie JL, Tang JM, Shu B, Chen L, et al. Effects of Human Bone Marrow Mesenchymal Stem Cells on Burn Injury Healing in a Mouse Model. Int J Clin Exp Pathol 2013;6:1327-36.

[16] Abdullahi A, Amini-Nik S, Jeschke MG. Animal Models in Burn Research. Cell Mol Life Sci 2014;71:3241-55.

[17] Hew JJ, Parungao RJ, Shi H, Tsai KH, Kim S, Ma D, et al. Mouse Models in Burns Research: Characterisation of the Hypermetabolic Response to Burn Injury. Burns 2020;46:663-74.

[18] Calum H, Høiby N, Moser C. Burn Mouse Models. Methods Mol Biol 2014;1149:793-802.

[19] Luze H, Kotzbeck P, Nischwitz SP, Kamolz LP. Importance of Accurate and Reproducible Animal Models for Burn Wounds. Burns 2020;46:1479-80.

[20] Reczyńska K, Tharkar P, Kim SY, Wang Y, Pamuła E, Chan HK, et al. Animal Models of Smoke Inhalation Injury and Related Acute and Chronic Lung Diseases. Adv Drug Deliv Rev 2018;123:107-34.

[21] Cetinkale O, Senel O, Bulan R. The Effect of Antioxidant Therapy on Cell-mediated Immunity Following Burn Injury in an Animal Model. Burns 1999;25:113-8.

[22] Hashemi SS, Pourfath MR, Derakhshanfar A, BehzadBehbahani A, Moayedi J. The Role of Labeled Cell Therapy with and Without Scaffold in Early Excision Burn Wounds in a Rat Animal Model. Iran J Basic Med Sci 2020;23:673-9.

[23] Oryan A, Alemzadeh E. Comparison of Botulinum Toxin Type A and Aprotinin Monotherapy with Combination Therapy in Healing of Burn Wounds in an Animal Model. Mol Biol Rep 2020;47:2693-702.

[24] Kocaman N, Altun S, Bal A, Ozcan EC, Sarac M, Artas G, et al. Effects of Carnosine, Ankaferd, and Silver Sulfadiazine on an Experimental Burn Model: Roles of Irisin and HSP70. J Burn Care Res 2021;42:408-14.

[25] Yagi H, Soto-Gutierrez A, Kitagawa Y, Tilles AW, Tompkins RG, Yarmush ML. Bone Marrow Mesenchymal Stromal Cells Attenuate Organ Injury Induced by LPS and Burn. Cell Transplant 2010;19:823-30.

[26] Yang J, Ma K, Zhang C, Liu Y, Liang F, Hu W, et al. Burns Impair Blood-Brain Barrier and Mesenchymal Stem Cells Can Reverse the Process in Mice. Front Immunol 2020;11:578879.

[27] Caliari-Oliveira C, Yaochite JN, Ramalho LN, Palma PV, Carlos D, Cunha Fde Q, et al. Xenogeneic Mesenchymal Stromal Cells Improve Wound Healing and Modulate the Immune Response in an Extensive Burn Model. Cell Transplant 2016;25:201-15.

[28] Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA Statement for Reporting Systematic Reviews and Meta-analyses of Studies that Evaluate Healthcare Interventions: Explanation and Elaboration. BMJ 2009;339:b2700.

[29] Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE’s Risk of Bias Tool for Animal Studies. BMC Med Res Methodol 2014;14:43.

[30] Lu G, Huang S, Chen Y, Ma K. Umbilical Cord Mesenchymal Stem Cell Transplantation Ameliorates Burn-induced Acute Kidney Injury in Rats. Int J Low Extrem Wounds 2013;12:205-11.

[31] Zhang J, La X, Fan L, Li P, Yu Y, Huang Y, et al. Immunosuppressive Effects of Mesenchymal Stem Cell Transplantation in Rat Burn Models. Int J Clin Exp Pathol 2015;8:5129-36.

[32] Li X, Liu L, Yang J, Yu Y, Chai J, Wang L, et al. Exosome Derived From Human Umbilical Cord Mesenchymal Stem Cell Mediates MiR-181c Attenuating Burn-induced Excessive Inflammation. EBioMedicine 2016;8:72-82.

[33] Liu JS, Du J, Cheng X, Zhang XZ, Li Y, Chen XL. Exosomal miR-451 from Human Umbilical Cord Mesenchymal Stem Cells Attenuates Burn-induced Acute Lung Injury. J Chin Med Assoc 2019;82:895-901.

[34] Curtis BJ, Shults JA, Boe DM, Ramirez L, Kovacs EJ. Mesenchymal Stem Cell Treatment Attenuates Liver and Lung Inflammation after Ethanol Intoxication and Burn Injury. Alcohol 2019;80:139-48.

[35] Beynen A, Gärtner K, Van Zutphen L. Standardization of animal experimentation. In: Principles of Laboratory Animal Science: A Contribution to the Humane Use and Care of Animals and to the Quality of Experimental Results. 2nd ed. Amsterdam: Elsevier; 2001. p. 103-10.

[36] Clough G. Environmental Effects on Animals Used in Biomedical Research. Biol Rev Camb Philos Soc 1982;57:487-523.

[37] Johnston NA, Nevalainen T. Impact of the biotic and abiotic environment on animal experiments. In: Handbook of Laboratory Animal Science, Volume 1: Essential Principles and Practices. Boca Raton, Florida: CRC Press; 2002. p. 311.

[38] Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101:1644-55.

[39] Pittet D, Rangel-Frausto S, Li N, Tarara D, Costigan M, Rempe L, et al. Systemic Inflammatory Response Syndrome, Sepsis, Severe Sepsis and Septic Shock: Incidence, Morbidities and Outcomes in Surgical ICU Patients. Intensive Care Med 1995;21:302-9.

[40] Talmor M, Hydo L, Barie PS. Relationship of Systemic Inflammatory Response Syndrome to Organ Dysfunction, Length of Stay, and Mortality in Critical Surgical Illness: Effect of Intensive Care Unit Resuscitation. Arch Surg 1999;134:81-7.

[41] Sheridan RL, Ryan CM, Yin LM, Hurley J, Tompkins RG. Death in the Burn Unit: Sterile Multiple Organ Failure. Burns 1998;24:307-11.

[42] Ryan CM, Schoenfeld DA, Thorpe WP, Sheridan RL, Cassem EH, Tompkins RG. Objective Estimates of the Probability of Death from Burn Injuries. N Engl J Med 1998;338:362-6.

[43] Gando S, Nanzaki S, Kemmotsu O. Disseminated Intravascular Coagulation and Sustained Systemic Inflammatory Response Syndrome Predict Organ Dysfunctions after Trauma: Application of Clinical Decision Analysis. Ann Surg 1999;229:121-7.

[44] Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP. The Natural History of the Systemic Inflammatory Response Syndrome (SIRS). A Prospective Study. JAMA 1995;273:117-23.

[45] Wolf SE, Rose JK, Desai MH, Mileski JP, Barrow RE, Herndon DN. Mortality Determinants in Massive Pediatric Burns. An Analysis of 103 Children with > or = 80% TBSA Burns (> or = 70% full-thickness). Ann Surg 1997;225:554-65.

[46] Takeda K, Akira S. Toll-like Receptors. Curr Protoc Immunol 2015;109:14.12.1-10.

[47] Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, et al. Circulating Mitochondrial DAMPs Cause Inflammatory Responses to Injury. Nature 2010;464:104-7.

[48] D’Arpa P, Leung KP. Toll-Like Receptor Signaling in Burn Wound Healing and Scarring. Adv Wound Care (New Rochelle) 2017;6:330-43.

[49] Akira S. TLR signaling. Curr Top Microbiol Immunol 2006;311:1-16.

[50] Paterson HM, Murphy TJ, Purcell EJ, Shelley O, Kriynovich SJ, Lien E, et al. Injury Primes the Innate Immune System for Enhanced Toll-like Receptor Reactivity. J Immunol 2003;171:1473-83.

[51] Adib-Conquy M, Cavaillon JM. Compensatory Antiinflammatory Response Syndrome. Thromb Haemost 2009;101:36-47.

[52] Yeh FL, Shen HD, Fang RH. Deficient Transforming Growth Factor Beta and Interleukin-10 Responses Contribute to the Septic Death of Burned Patients. Burns 2002;28:631-7.

[53] Vanzant EL, Lopez CM, Ozrazgat-Baslanti T, Ungaro R, Davis R, Cuenca AG, et al. Persistent Inflammation, Immunosuppression, and Catabolism Syndrome after Severe Blunt Trauma. J Trauma Acute Care Surg 2014;76:21-9.

[54] Ding DC, Shyu WC, Lin SZ. Mesenchymal Stem Cells. Cell Transplant 2011;20:5-14.

[55] Colter DC, Class R, DiGirolamo CM, Prockop DJ. Rapid Expansion of Recycling Stem Cells in Cultures of Plasticadherent Cells from Human Bone Marrow. Proc Natl Acad Sci U S A 2000;97:3213-8.

[56] Heo JS, Choi Y, Kim HS, Kim HO. Comparison of Molecular Profiles of Human Mesenchymal Stem Cells Derived from Bone Marrow, Umbilical Cord Blood, Placenta and Adipose Tissue. Int J Mol Med 2016;37:115-25.

[57] Denburg JA, Inman MD, Sehmi R, Uno M, O’Byrne PM. Hemopoietic Mechanisms in Allergic Airway Inflammation. Int Arch Allergy Immunol 1998;117:155-9.

[58] Denburg JA, Inman MD, Wood L, Ellis R, Sehmi R, Dahlback M, et al. Bone Marrow Progenitors in Allergic Airways Diseases: Studies in Canine and Human Models. Int Arch Allergy Immunol 1997;113:181-3.

[59] Steinberger Z, Xu H, Kazmers NH, Chen CD, Caron RJ, Qin L, et al. Robustness Testing of Mesenchymal Stem Cell Monotherapy Following Vascularized Composite Allotransplantation. J Reconstr Microsurg 2020;36:397-402.

[60] Puissant B, Barreau C, Bourin P, Clavel C, Corre J, Bousquet C, et al. Immunomodulatory Effect of Human Adipose Tissue-derived Adult Stem Cells: Comparison with Bone Marrow Mesenchymal Stem Cells. Br J Haematol 2005;129:118-29.

[61] Yañez R, Lamana ML, García-Castro J, Colmenero I, Ramírez M, Bueren JA. Adipose Tissue-derived Mesenchymal Stem Cells Have In Vivo Immunosuppressive Properties Applicable for the Control of the Graft-versushost Disease. Stem Cells 2006;24:2582-91.

[62] Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, et al. Human Leukocyte Antigen-G5 Secretion by Human Mesenchymal Stem Cells is Required to Suppress T Lymphocyte and Natural Killer Function and to Induce CD4+CD25highFOXP3+ Regulatory T Cells. Stem Cells 2008;26:212-22.

[63] Chen CC, Chen RF, Shao JS, Li YT, Wang YC, BrandacherG, et al. Adipose-derived Stromal Cells Modulating Composite Allotransplant Survival is Correlated with B Cell Regulation in a Rodent Hind-limb Allotransplantation Model. Stem Cell Res Ther 2020;11:478.

[64] Zhang J, Rong Y, Luo C, Cui W. Bone Marrow Mesenchymal Stem Cell-derived Exosomes Prevent Osteoarthritis by Regulating Synovial Macrophage Polarization. Aging (Albany NY) 2020;12:25138-52.

[65] Németh K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, et al. Bone Marrow Stromal Cells Attenuate Sepsis via Prostaglandin E(2)-dependent Reprogramming of Host Macrophages to Increase their Interleukin-10 Production. Nat Med 2009;15:42-9.

[66] Zhou T, Sun Y, Wang Y, Chen X, Zhuo L, Bu L, et al. Umbilical Cord Blood Mesenchymal Stem Cells Enhance Lipopolysaccharide-Induced IL-10 and IL-37 Production in THP-1 Cells. Inflammation 2019;42:987-93.

[67] Ng SL, Leno-Duran E, Samanta D, Almo SC, Strominger JL. Genetically Modified Hematopoietic Stem/Progenitor Cells that Produce IL-10-Secreting Regulatory T Cells. Proc Natl Acad Sci U S A 2019;116:2634-9.

[68] Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, et al. Human Mesenchymal Stem Cells Modulate B-Cell Functions. Blood 2006;107:367-72.

[69] Ramasamy R, Fazekasova H, Lam EW, Soeiro I, Lombardi G, Dazzi F. Mesenchymal Stem Cells Inhibit Dendritic Cell Differentiation and Function by Preventing Entry into the Cell Cycle. Transplantation 2007;83:71-6.

[70] Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L. Mesenchymal stem cell-natural Killer Cell Interactions: Evidence that Activated NK Cells are Capable of Killing MSCs, Whereas MSCs can Inhibit IL-2-induced NK-cell Proliferation. Blood 2006;107:1484-90.

[71] Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, et al. Role for Interferon-gamma in the Immunomodulatory Activity of Human Bone Marrow Mesenchymal Stem Cells. Stem Cells 2006;24:386-98.

[72] Ryan JM, Barry F, Murphy JM, Mahon BP. Interferon-gamma does not Break, but Promotes the Immunosuppressive Capacity of Adult Human Mesenchymal Stem Cells. Clin Exp Immunol 2007;149:353-63.

[73] Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, et al. Mesenchymal Stem Cell-Mediated Immunosuppression Occurs Via Concerted Action of Chemokines and Nitric Oxide. Cell Stem Cell 2008;2:141-50.

[74] DelaRosa O, Lombardo E, Beraza A, Mancheño-Corvo P, Ramirez C, Menta R, et al. Requirement of IFN-gammamediated Indoleamine 2,3-dioxygenase Expression in the Modulation of Lymphocyte Proliferation by Human Adipose-derived Stem Cells. Tissue Eng Part A 2009;15:2795-806.

[75] Luk F, de Witte SF, Korevaar SS, Roemeling-van Rhijn M, Franquesa M, Strini T, et al. Inactivated Mesenchymal Stem Cells Maintain Immunomodulatory Capacity. Stem Cells Dev 2016;25:1342-54.

[76] Zhang L, Yu D. Exosomes in Cancer Development, Metastasis, and Immunity. Biochim Biophys Acta Rev Cancer 2019;1871:455-68.

[77] Kalluri R, LeBleu VS. The Biology, Function, and Biomedical Applications of Exosomes. Science 2020;367:eaau6977.

[78] Zhang H, Freitas D, Kim HS, Fabijanic K, Li Z, Chen H, et al. Identification of Distinct Nanoparticles and Subsets of Extracellular Vesicles by Asymmetric Flow Field-flow Fractionation. Nat Cell Biol 2018;20:332-43.

[79] Keerthikumar S, Chisanga D, Ariyaratne D, Al Saffar H, Anand S, Zhao K, et al. ExoCarta: A Webbased Compendium of Exosomal Cargo. J Mol Biol 2016;428:688-92.

[80] Chen Z, Xue S, Zhang S, Cheng K, Ye Q. Exosomes from Donor-derived Adipose Mesenchymal Stem Cells Prolong the Survival of Vascularized Composite Allografts. J Cell Physiol 2021;236:5895-905.

[81] Sungkar T, Putra A, Lindarto D, Sembiring RJ. Intravenous Umbilical Cord-derived Mesenchymal Stem Cells Transplantation Regulates Hyaluronic Acid and Interleukin-10 Secretion Producing Low-grade Liver Fibrosis in Experimental Rat. Med Arch 2020;74:177-82.

[82] Jeschke MG. The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes? Mol Med 2009;15:337-51.

[83] Gong Y, Long X, Xu H, Yang X, Guo Q. The Changes and Prognostic Value of liver function in Young Adults with Severe Burn: A Retrospective Observational Study. Medicine (Baltimore) 2018;97:e13721.

[84] Barret JP, Jeschke MG, Herndon DN. Fatty Infiltration of the Liver in Severely Burned Pediatric Patients: Autopsy Findings and Clinical Implications. J Trauma 2001;51:736-9.

[85] Jeschke MG, Micak RP, Finnerty CC, Herndon DN. Changes in Liver Function and Size after a Severe Thermal Injury. Shock 2007;28:172-7.

[86] Steller H. Mechanisms and Genes of Cellular Suicide. Science 1995;267:1445-9.

[87] Ramzy PI, Wolf SE, Irtun O, Hart DW, Thompson JC, Herndon DN. Gut Epithelial Apoptosis after Severe Burn: Effects of Gut Hypoperfusion. J Am Coll Surg 2000;190:281-7.

[88] Bellas RE, FitzGerald MJ, Fausto N, Sonenshein GE. Inhibition of NF-kappa B Activity Induces Apoptosis in Murine Hepatocytes. Am J Pathol 1997;151:891-6.

[89] Strasser A, O’Connor L, Dixit VM. Apoptosis Signaling. Annu Rev Biochem 2000;69:217-45.

[90] Gauglitz GG, Song J, Herndon DN, Finnerty CC, Boehning D, Barral JM, et al. Characterization of the Inflammatory Response during Acute and Post-acute Phases after Severe Burn. Shock 2008;30:503-7.

[91] Jeschke MG, Boehning DF, Finnerty CC, Herndon DN. Effect of Insulin on the Inflammatory and acute Phase Response after Burn Injury. Crit Care Med 2007;35:S519-23.

[92] Carson J, Goverman J, Fagan SP. 31 Acute Renal Failure in Association with Thermal Injury. Total Burn Care E-Book. 2017;20:318-327.

[93] Kellum JA. Acute Kidney Injury. Crit Care Med. 2008;36(4 Suppl):S141-145.

[94] Cartotto R, Choi J, Gomez M, Cooper A. A Prospective Study on the Implications of a Base Deficit during Fluid Resuscitation. J Burn Care Rehabil 2003;24:75-84.

[95] Schrier RW, Wang W. Acute Renal Failure and Sepsis. N Engl J Med 2004;351:159-69.

[96] Hohlfeld T, Klemm P, Thiemermann C, Warner TD, Schrör K, Vane JR. The Contribution of Tumour Necrosis Factor-alpha and Endothelin-1 to the Increase of Coronary Resistance in Hearts from Rats Treated with Endotoxin. Br J Pharmacol 1995;116:3309-15.

[97] Kallinen O, Maisniemi K, Böhling T, Tukiainen E, Koljonen V. Multiple Organ Failure as a Cause of Death in Patients with Severe Burns. J Burn Care Res 2012;33:206-11.

[98] Kraft R, Herndon DN, Finnerty CC, Shahrokhi S, Jeschke MG. Occurrence of Multiorgan Dysfunction in Pediatric Burn Patients: Incidence and Clinical Outcome. Ann Surg 2014;259:381-7.

[99] de Albuquerque IM, Pasqualoto AS, Trevisan ME, Gonçalves MP, Badaró AF, de Moraes JP, et al. Role of Physiotherapy in the Rehabilitation of Survivors of the Kiss Nightclub Tragedy in Santa Maria, Brazil. Physiotherapy 2013;99:269-70.

[100] Tobe E. Progressive Neuropsychiatric and Brain Abnormalities after Smoke Inhalation. BMJ Case Rep 2012;2012:bcr0220125945.

[101] Randolph AC, Fukuda S, Ihara K, Enkhbaatar P, Micci MA. Blood-Brain Barrier Dysfunction after Smoke Inhalation Injury, With and Without Skin Burn. Shock 2019;51:634-49.

[102] He X, Ai S, Guo W, Yang Y, Wang Z, Jiang D, et al. Umbilical Cord-derived Mesenchymal Stem (Stromal) Cells for Treatment of Severe Sepsis: Aphase 1 Clinical Trial. Transl Res 2018;199:52-61.

[103] McIntyre LA, Stewart DJ, Mei SHJ, Courtman D, Watpool I, Granton J, et al. Cellular Immunotherapy for Septic Shock. A Phase I Clinical Trial. Am J Respir Crit Care Med 2018;197:337-47.

[104] Schlosser K, Wang JP, Dos Santos C, Walley KR, Marshall J, Fergusson DA, et al. Effects of Mesenchymal Stem Cell Treatment on Systemic Cytokine Levels in a Phase 1 Dose Escalation Safety Trial of Septic Shock Patients. Crit Care Med 2019;47:918-25.

[105] Swaminathan M, Kopyt N, Atta MG, Radhakrishnan J, Umanath K, Nguyen S, et al. Pharmacological Effects of ExVivo Mesenchymal Stem Cell Immunotherapy in Patients with Acute Kidney Injury and Underlying Systemic Inflammation. Stem Cells Transl Med 2021;10:1588-601.

[106] Perlee D, van Vught LA, Scicluna BP, Maag A, Lutter R, Kemper EM, et al. Intravenous Infusion of Human Adipose Mesenchymal Stem Cells Modifies the Host Response to Lipopolysaccharide in Humans: A Randomized, SingleBlind, Parallel Group, Placebo Controlled Trial. Stem Cells 2018;36:1778-88.

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