سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Soufizadeh, Parham, Nikbakht Brujeni, Gholamreza, Dehghan, Mohammad Mehdi, Jabbari Fakhr, Massoumeh, Houshmand, Pouya, Mohebbi, Mahyar, Aminianfar, Hossein, Sadeghian Chaleshtori, Sirous. (1404). Preventing the rejection of skin allografts by immunomodulatory and regenerative effects of exosomes derived from bone marrow mesenchymal stem cells in mice. , 28(4), 469-476. doi: 10.22038/ijbms.2025.82564.17841
Parham Soufizadeh; Gholamreza Nikbakht Brujeni; Mohammad Mehdi Dehghan; Massoumeh Jabbari Fakhr; Pouya Houshmand; Mahyar Mohebbi; Hossein Aminianfar; Sirous Sadeghian Chaleshtori. "Preventing the rejection of skin allografts by immunomodulatory and regenerative effects of exosomes derived from bone marrow mesenchymal stem cells in mice". , 28, 4, 1404, 469-476. doi: 10.22038/ijbms.2025.82564.17841
Soufizadeh, Parham, Nikbakht Brujeni, Gholamreza, Dehghan, Mohammad Mehdi, Jabbari Fakhr, Massoumeh, Houshmand, Pouya, Mohebbi, Mahyar, Aminianfar, Hossein, Sadeghian Chaleshtori, Sirous. (1404). 'Preventing the rejection of skin allografts by immunomodulatory and regenerative effects of exosomes derived from bone marrow mesenchymal stem cells in mice', , 28(4), pp. 469-476. doi: 10.22038/ijbms.2025.82564.17841
Soufizadeh, Parham, Nikbakht Brujeni, Gholamreza, Dehghan, Mohammad Mehdi, Jabbari Fakhr, Massoumeh, Houshmand, Pouya, Mohebbi, Mahyar, Aminianfar, Hossein, Sadeghian Chaleshtori, Sirous. Preventing the rejection of skin allografts by immunomodulatory and regenerative effects of exosomes derived from bone marrow mesenchymal stem cells in mice. , 1404; 28(4): 469-476. doi: 10.22038/ijbms.2025.82564.17841

Preventing the rejection of skin allografts by immunomodulatory and regenerative effects of exosomes derived from bone marrow mesenchymal stem cells in mice

Iranian Journal of Basic Medical Sciences
مقاله 8، دوره 28، شماره 4، تیر 2025، صفحه 469-476    اصل مقاله (592.09 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2025.82564.17841
نویسندگان
Parham Soufizadeh1، 2؛ Gholamreza Nikbakht Brujeni* 1، 3؛ Mohammad Mehdi Dehghan1، 4؛ Massoumeh Jabbari Fakhr1، 5؛ Pouya Houshmand1، 3؛ Mahyar Mohebbi4؛ Hossein Aminianfar1، 6؛ Sirous Sadeghian Chaleshtori1، 7
1Biomedical Research Institute, University of Tehran, Tehran, Iran
2Gene Therapy Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
3Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
4Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
5Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Qom University of Medical Sciences, Qom, Iran
6Department of Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
7Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
چکیده
Objective(s): Reducing the immune response to inflammation is vital for successful transplantation, yet chronic graft rejection remains a major issue despite immunosuppressive drugs. This study explored the effect of bone marrow mesenchymal stem cell-derived exosomes on the survival of skin allografts in mice.
Materials and Methods: C57BL/6 and BALB/c mice underwent skin allograft surgery, followed by intraperitoneal injection of exosomes, which were compared with groups receiving dexamethasone and no treatment group.
Results: On day 3, mild signs of graft rejection appeared in both control groups, while none were seen in the exosome-treated group. By day 14, the grafts were completely rejected in the control groups but showed mild rejection in the treatment group. Histopathology revealed severe rejection signs in the control groups, including epithelial necrosis and inflammation, while the treatment group showed signs of angiogenesis and graft acceptance. Additionally, inflammatory cytokine levels (TNF-α, IL-1β, and IL-6) were lower in the treatment group than in the positive control group, particularly on days 3 and 14.
Conclusion: The findings suggest that exosomes can prevent graft rejection and may offer a promising therapeutic approach for solid organ transplantation, though further research is needed to standardize exosome methods and evaluate cost-effectiveness.
کلیدواژه‌ها
Exosome؛ Immunomodulation؛ Mice؛ Mesenchymal stem cells؛ Regeneration؛ Transplantation
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مراجع
1. Shapiro R, Young JB, Milford EL, Trotter JF, Bustami RT, Leichtman AB. Immunosuppression: evolution in practice and trends, 1993–2003. Am J Transplant 2005; 5:874–886.
2.    Hanna RM, Abd-El-Malak F, Alnaser A, Cader R, Yabu JM. Herpes zoster in kidney transplant recipients: A series of three cases. Case Rep Nephrol Dial 2020; 10:139–146.
3.    Ebrahimi A, Rahim F. Recent immunomodulatory strategies in transplantation. Immunol Invest 2014; 43:829–837.
4.    Denton MD, Magee CC, Sayegh MH. Immunosuppressive strategies in transplantation. Lancet 1999; 353:1083–1091.
5.    Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant 2004; 4:378–383.
6.    Liu Q, Wang Y, Nakao A, Zhang W, Gorantla VS, Zheng XX. Heart allograft tolerance induced and maintained by vascularized hind-limb transplant in rats. Clin Dev Immunol 2013; 2013:1–6.
7.    Yakubu I, Haririan A, Bartlett ST, Sparkes T. Successful renal transplantation between identical twins with very brief immunosuppression. Case Rep Transplant 2018; 2018:1–5.
8.    Fangmann J, Dalchau R, Fabre JW. Rejection of skin allografts by indirect allorecognition of donor class I major histocompatibility complex peptides. Transplant Proc 1993; 25:183–184.
9.    Morelli AE. The immune regulatory effect of apoptotic cells and exosomes on dendritic cells: its impact on transplantation. Am J Transplant 2006; 6:254–261.
10.    Geissler EK, Schlitt HJ. Immunosuppression for liver transplantation. Gut 2009; 58:452–463.
11.    Gupta SK. Induction immunosuppression and post-transplant diabetes mellitus: A propensity-matched cohort study. Front Endocrinol (Lausanne) 2023; 14:1248940.
12.    Helmuth ME, Liu Q, Turenne MN, Park JM, Oguntimein M, Dutcher SK, et al. Secular trends in the cost of immunosuppressants after solid organ transplantation in the United States. Clin J Am Soc Nephrol 2019; 14:421–430.
13.    Gea-Banacloche JC. Immunomodulation. In: Principles of Molecular Medicine. Totowa, NJ: Humana Press; 2006:893–904.
14.    Devlin J, Doherty DG, Thomson LJ, Wong T, Donaldson P, Portmann B, et al. Defining the outcome of immunosuppression withdrawal after liver transplantation. Hepatology 1998; 27:926–933.
15.    Kurian MT, Rabbani SA, Thomas AC, Javed N. Coronavirus disease 2019 (COVID-19) in a kidney transplant recipient; case report. J Nephropathol 2021; 11:e9–e9.
16.    Le Blanc K, Ringdén O. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med 2007; 262:509–525.
17.    Wiesner RH, Demetris AJ, Belle SH, Seaberg EC, Lake JR, Zetterman RK, et al. Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. Hepatology 1998; 28:638–645.
18.    Rahmati S, Shojaei F, Shojaeian A, Rezakhani L, Dehkordi MB. An overview of current knowledge in biological functions and potential theragnostic applications of exosomes. Chem Phys Lipids 2020; 226:104836.
19.    Butcher JA, Hariharan S, Adams MB, Johnson CP, Roza AM, Cohen EP. Renal transplantation for end-stage renal disease following bone marrow transplantation: a report of six cases, with and without immunosuppression. Clin Transplant 1999; 13:330–335.
20.    Jiang L, Zhang S, Hu H, Yang J, Wang XY, Ma Y, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acute liver failure by reducing the activity of the NLRP3 inflammasome in macrophages. Biochem Biophys Res Commun 2019; 508:735–741.
21.    Quiñones-Vico MI, Sanabria-de la Torre R, Sánchez-Díaz M, Sierra-Sánchez Á, Montero-Vílchez T, Fernández-González A, et al. The role of exosomes derived from mesenchymal stromal cells in dermatology. Front Cell Dev Biol 2021; 9:647012.
22.    Nadri S, Soleimani M, Hosseni RH, Massumi M, Atashi A, Izadpanah R. An efficient method for isolation of murine bone marrow mesenchymal stem cells. Int J Dev Biol 2007; 51:723–729.
23.    Talbott HE, Mack KL, Guardino N, Parker JMR, Spielman A, Davitt MF, et al. Allele-specific expression reveals genetic drivers of tissue regeneration in mice. Cell Stem Cell 2023; 30:1368-1381.
24.    Pakyari M, Farokhi A, Khosravi-Maharlooei M, Kilani RT, Ghahary A, Brown E. A new method for skin grafting in murine model. Wound Repair Regen 2016; 24:695–704.
25.    Kellersmann R, Zhong R. Surgical technique for skin transplantation in mice. In: Organtransplantation in rats and mice. 1998; Vol: ???151–154.
26.    Mayumi H, Nomoto K, Good RA. A surgical technique for experimental free skin grafting in mice. Jpn J Surg 1988; 18:548–557.
27.    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 2001; 25:402–408.
28.    Zhao Y, Chen S, Lan P, Wu C, Yu D, Xiao X, et al. Macrophage subpopulations and their impact on chronic allograft rejection versus graft acceptance in a mouse heart transplant model. Am J Transplant 2018; 18:604–616.
29.    Miyairi S, Ueda D, Yagisawa T, Okada D, Keslar K, Tanabe K, et al. Recipient myeloperoxidase-producing cells regulate antibody-mediated acute versus chronic kidney allograft rejection. JCI Insight 2021; 6:e144580.
30.    Abe T, Ishii D, Gorbacheva V, Kohei N, Tsuda H, Tanaka T, et al. Anti-huCD20 antibody therapy for antibody-mediated rejection of renal allografts in a mouse model. Am J Transplant 2015; 15:1192–1204.
31.    Reichenbach DK, Li Q, Hoffman RA, Williams AL, Shlomchik WD, Rothstein DM, et al. Allograft outcomes in outbred mice. Am J Transplant 2013; 13:580–588.
32.    Goral S, Brukamp K, Ticehurst EH, Abt PL, Bloom RD, Kearns J, et al. Transplant nephrectomy: Histologic findings - A single center study. Am J Nephrol 2014; 40:491–498.
33.    Zhao X, Zhang K, Daniel P, Wisbrun N, Fuchs H, Fan H. Delayed allogeneic skin graft rejection in CD26-deficient mice. Cell Mol Immunol 2019; 16:557–567.
34.    Helwa I, Cai J, Drewry M, Zimmerman AD, Dinkins MB, Khaled ML, et al. A comparative study of serum exosome isolation using differential ultracentrifugation and three commercial reagents. PLoS One 2017; 12:e0170628.
35.    Zhao L, Yu J, Wang J, Li H, Che J, Cao B. Isolation and identification of miRNAs in exosomes derived from serum of colon cancer patients. J Cancer 2017; 8:1145–1152.
36.    Tang Y, Huang Y, Zheng L, Qin S, Xu X, An T, et al. Comparison of isolation methods of exosomes and exosomal RNA from cell culture medium and serum. Int J Mol Med 2017; 40:834–844.
37.    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.
38.    Chen W, Huang Y, Han J, Yu L, Li Y, Lu Z, et al. Immunomodulatory effects of mesenchymal stromal cells-derived exosome. Immunol Res 2016; 64:831–840.
39.    Li C, Guo F, Wang X, Liu D, Wu B, Wang F, et al. Exosome-based targeted RNA delivery for immune tolerance induction in skin transplantation. J Biomed Mater Res A 2020; 108:1493–1500.
40.    Wen D, Peng Y, Liu D, Weizmann Y, Mahato RI. Mesenchymal stem cell and derived exosome as small RNA carrier and immunomodulator to improve islet transplantation. J Control Release 2016; 238:166–175.
41.    Lai P, Chen X, Guo L, Wang Y, Liu X, Liu Y, et al. A potent immunomodulatory role of exosomes derived from mesenchymal stromal cells in preventing cGVHD. J Hematol Oncol 2018; 11:135-149.
42.    Pirenne J, Pirenne-Noizat F, de Groote D, Vrindts Y, Lopez M, Gathy R, et al. Cytokines and organ transplantation: A review. Nucl Med Biol 1994; 21:545–555.
43.    Wu P, Zhang B, Shi H, Qian H, Xu W. MSC-exosome: A novel cell-free therapy for cutaneous regeneration. Cytotherapy 2018; 20:291–301.
44.    Urzì O, Bagge RO, Crescitelli R. The dark side of foetal bovine serum in extracellular vesicle studies. J Extracell Vesicles 2022; 11:e12248.

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