So sánh tác động của các tác nhân mô phỏng tình trạng thiếu oxy lên các con đường tín hiệu liên quan đến sự di chuyển của tế bào gốc trung mô

Cell and Tissue Banking - Tập 21 - Trang 643-653 - 2020
Asieh Heirani-Tabasi1, Mahdi Mirahmadi1, Mohammad Amir Mishan2, Hojjat Naderi-Meshkin1, Shirin Toosi1, Maryam M. Matin1,3,4, Hamid Reza Bidkhori1, Ahmad Reza Bahrami1,3,4
1Stem Cells and Regenerative Medicine Research Group, Academic Center for Education, Culture and Research (ACECR), Khorasan Razavi Branch, Mashhad, Iran
2Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3Cell and Molecular Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
4Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

Tóm tắt

Các tế bào gốc trung mô có nguồn gốc từ mỡ (Ad-MSCs) đã được xác định là những tác nhân đầy hứa hẹn cho các ứng dụng lâm sàng nhờ khả năng dễ tiếp cận, phân hóa đa dòng và khả năng điều biến miễn dịch. Tuy nhiên, điều kiện giao tế bào tối ưu vẫn là một thách thức lâm sàng và việc cải thiện khả năng định vị tế bào gốc tới các cơ quan mục tiêu đang được xem xét như một chiến lược chính trong việc tiêm tế bào liệu pháp toàn thân. Đã có dấu hiệu cho thấy khả năng định vị của tế bào gốc trung mô tăng lên khi được điều trị bằng các yếu tố mô phỏng tình trạng thiếu oxy, tuy nhiên, hiệu quả của các tác nhân khác nhau vẫn cần được xác định. Trong nghiên cứu này, các tác nhân mô phỏng tình trạng thiếu oxy, bao gồm axit valproic (VPA), cobalt chloride (CoCl2) và deferoxamine (DFX) đã được xem xét để xác định liệu chúng có thể kích hoạt các phân tử tín hiệu liên quan đến sự di chuyển của Ad-MSCs trong môi trường in vitro hay không. Chúng tôi báo cáo rằng, các Ad-MSCs được điều trị bằng DFX dẫn đến việc tăng đáng kể biểu hiện mRNA của MAPK4 (liên quan đến con đường tín hiệu MAPK), INPP4B (liên quan đến con đường inositol polyphosphate), VEGF-A và VEGF-C (liên quan đến các con đường cytokine-receptor), IL-8 và thụ thể của nó, CXCR2 (liên quan đến con đường tín hiệu IL-8). Trong khi các tế bào được điều trị bằng VPA không cho thấy những tác động như vậy và CoCl2 chỉ làm tăng biểu hiện gen VEGF-A và VEGF-C. Hơn nữa, kết quả từ các thử nghiệm chữa lành vết thương cho thấy khả năng di chuyển của Ad-MSCs được điều trị bằng DFX đã tăng lên đáng kể sau 8 và 24 giờ điều trị. Nghiên cứu này cung cấp bằng chứng đáng tin cậy về DFX, có thể là một loại thuốc hiệu quả cho việc tiền điều trị dược lý của Ad-MSCs nhằm tăng cường khả năng định vị và tái tạo các mô bị tổn thương thông qua việc kích hoạt các con đường tín hiệu liên quan đến sự di chuyển.

Từ khóa

#tế bào gốc trung mô #Ad-MSCs #tác nhân mô phỏng thiếu oxy #DFX #khả năng di chuyển #tín hiệu MAPK

Tài liệu tham khảo

Al-Sowayan B, Keogh RJ, Abumaree M, Georgiou HM, Kalionis B (2019) Valproic acid stimulates in vitro migration of the placenta-derived mesenchymal stem/stromal cell line CMSC29. Stem Cell Investig 6:3 Bancroft CC, Chen Z, Dong G, Sunwoo JB, Yeh N, Park C, Van Waes C (2001) Coexpression of proangiogenic factors IL-8 and VEGF by human head and neck squamous cell carcinoma involves coactivation by MEK-MAPK and IKK-NF-κB signal pathways. Clin Cancer Res 7:435–442 Campbell M, Trimble ER (2005) Modification of PI3K-and MAPK-dependent chemotaxis in aortic vascular smooth muscle cells by protein kinase CβII. Circ Res 96:197–206 Chen Y, Tsai Y-H, Tseng S-H (2012) Valproic acid affected the survival and invasiveness of human glioma cells through diverse mechanisms. J Neurooncol 109:23–33 Chen L, Cui X, Wu Z, Jia L, Yu Y, Zhou Q et al (2014) Transplantation of bone marrow mesenchymal stem cells pretreated with valproic acid in rats with an acute spinal cord injury. Biosci Trends 8:111–119 Deezagi A, Shomali S (2018) Prostaglandin F-2α stimulates the secretion of vascular endothelial growth factor and induces cell proliferation and migration of adipose tissue derived mesenchymal stem cells. Cell J 20:259–266 Fu X, Liu G, Halim A, Ju Y, Luo Q, Song G (2019) Mesenchymal stem cell migration and tissue repair. Cells 8:784 Gasser JA, Inuzuka H, Lau AW, Wei W, Beroukhim R, Toker A (2014) SGK3 mediates INPP4B-dependent PI3K signaling in breast cancer. Mol Cell 56:595–607 Gimble JM, Katz AJ, Bunnell BA (2007) Adipose-derived stem cells for regenerative medicine. Circ Res 100:1249–1260 Guo M, Song L-P, Jiang Y, Liu W, Yu Y, Chen G-Q (2006) Hypoxia-mimetic agents desferrioxamine and cobalt chloride induce leukemic cell apoptosis through different hypoxia-inducible factor-1α independent mechanisms. Apoptosis 11:67–77 Hashemzadeh MR, Seyedi Z, Rafiei S, Hassanzadeh-Moghaddam M, Edalatmanesh MA (2017) Chemokine receptor’s expression in human adipose derived mesenchymal stem cells primed with valproic acid. Comp Clin Path 26:115–120 Heirani-Tabasi A, Toosi S, Mirahmadi M, Mishan MA, Bidkhori HR, Bahrami AR et al (2017) Chemokine receptors expression in MSCs: comparative analysis in different sources and passages. Tissue Eng Regen Med 14:605–615 Heirani-Tabasi A, Naderi-Meshkin H, Matin MM, Mirahmadi M, Shahriyari M, Ahmadiankia N et al (2018) Augmented migration of mesenchymal stem cells correlates with the subsidiary CXCR4 variant. Cell Adh Migr 12:118–126 Hu C, Zhao L, Li L (2019) Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases. Stem Cell Res Ther 10:199 Hung S-C, Pochampally RR, Hsu S-C, Sanchez C, Chen S-C, Spees J, Prockop DJ (2007) Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo. PloS ONE 2:e416 Jeong H-J, Chung H-S, Lee B-R, Kim S-J, Yoo S-J, Hong S-H, Kim H-M (2003) Expression of proinflammatory cytokines via HIF-1α and NF-κB activation on desferrioxamine-stimulated HMC-1 cells. Biochem Biophys Res Commun 306:805–811 Kuhbier JW, Weyand B, Radtke C, Vogt PM, Kasper C, Reimers K (2010) Isolation, characterization, differentiation, and application of adipose-derived stem cells. Adv Biochem Eng Biotechnol 123:55–105 Lee H-J, Lee J, Lee S-K, Lee S-K, Kim E-C (2007) Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes. BMC Cancer 7:176 Li A, Dubey S, Varney ML, Dave BJ, Singh RK (2003) IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J Immunol 170:3369–3376 Liu H, Xue W, Ge G, Luo X, Li Y, Xiang H et al (2010) Hypoxic preconditioning advances CXCR4 and CXCR7 expression by activating HIF-1α in MSCs. Biochem Biophys Res Commun 401:509–515 Liu GS, Peshavariya HM, Higuchi M, Chan EC, Dusting GJ, Jiang F (2016) Pharmacological priming of adipose-derived stem cells for paracrine VEGF production with deferoxamine. J Tissue Eng Regen Med 10:E167–E176 Liu L, Chen J-X, Zhang X-W, Sun Q, Yang L, Liu A et al (2018) Chemokine receptor 7 overexpression promotes mesenchymal stem cell migration and proliferation via secreting Chemokine ligand 12. Sci Rep 8:204 Locke M, Windsor J, Dunbar PR (2009) Human adipose-derived stem cells: isolation, characterization and applications in surgery. ANZ J Surg 79:235–244 Masoud Y, Ramin S, Mahboobeh R, Mehrnoosh M, Fahimeh J, Parastoo K (2019) Effect of lithium and valproate on proliferation and migration of limbal epithelial stem/progenitor cells. Curr Eye Res 44:154–161 Mirahmadi M, Rezanejadbardaji H, Irfan-Maqsood M, Mokhtari MJ, Naderi-Meshkin H (2016a) Stem cell therapy for neurodegenerative diseases: strategies for regeneration against degeneration. Cell Ther Regen Med J 1:3 Mirahmadi M, Ahmadiankia N, Naderi-Meshkin H, Heirani-Tabasi A, Bidkhori HR, Afsharian P, Bahrami AR (2016b) Hypoxia and laser enhance expression of SDF-1 in muscles cells. Cell Mol Biol 62:31–37 Mishan MA, Heirani-Tabasi A, Mokhberian N, Hassanzade M, Moghaddam HK, Bahrami AR, Ahmadiankia N (2015) Analysis of chemokine receptor gene expression in esophageal cancer cells compared with breast cancer with insights into metastasis. Iran J Public Health 44:1353–1358 Mishan MA, Ahmadiankia N, Bahrami AR (2016) CXCR4 and CCR7: Two eligible targets in targeted cancer therapy. Cell Biol Int 40:955–967 Naderi-Meshkin H, Bahrami AR, Bidkhori HR, Mirahmadi M, Ahmadiankia N (2015) Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy. Cell Biol Int 39:23–34 Naderi-Meshkin H, Matin MM, Heirani‐Tabasi A, Mirahmadi M, Irfan‐Maqsood M, Edalatmanesh MA et al (2016) Injectable hydrogel delivery plus preconditioning of mesenchymal stem cells: exploitation of SDF‐1/CXCR4 axis toward enhancing the efficacy of stem cells’ homing. Cell Biol Int 40:730–741 Onda K, Yoshida H, Hayakari R, Xing F, Wang L, Matsumiya T et al (2016) Desferrioxamine, an iron chelator, induces CXCL8 expression in U373MG human astrocytoma cells. Hirosaki Med J 66:127–134 Oses C, Olivares B, Ezquer M, Acosta C, Bosch P, Donoso M et al (2017) Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: potential application in the treatment of diabetic neuropathy. PLoS One 12:e0178011 Peyvandi A, Abbaszadeh HA, Roozbahany NA, Pourbakht A, Khoshsirat S, Niri HH, Peyvandi H, Niknazar S (2018) Deferoxamine promotes mesenchymal stem cell homing in noise-induced injured cochlea through PI 3K/AKT pathway. Cell Prolif 51:e12434 Sharma M, Afrin F, Tripathi R, Gangenahalli G (2013) Regulated expression of CXCR4 constitutive active mutants revealed the up-modulated chemotaxis and up-regulation of genes crucial for CXCR4 mediated homing and engraftment of hematopoietic stem/progenitor cells. J Stem Cells Regen Med 9:19–27 Sinn D-I, Kim S-J, Chu K, Jung K-H, Lee S-T, Song E-C et al (2007) Valproic acid-mediated neuroprotection in intracerebral hemorrhage via histone deacetylase inhibition and transcriptional activation. Neurobiol Dis 26:464–472 Smith AN, Willis E, Chan VT, Muffley LA, Isik FF, Gibran NS, Hocking AM (2010) Mesenchymal stem cells induce dermal fibroblast responses to injury. Exp Cell Res 316:48–54 Spaeth E, Klopp A, Dembinski J, Andreeff M, Marini F (2008) Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther 15:730–738 Tang H, Sun Y, Shi Z, Huang H, Fang Z, Chen J et al (2013) YKL-40 induces IL-8 expression from bronchial epithelium via MAPK (JNK and ERK) and NF-κB pathways, causing bronchial smooth muscle proliferation and migration. J Immunol 190:438–446 Timoshenko A, Rastogi S, Lala P (2007) Migration-promoting role of VEGF-C and VEGF-C binding receptors in human breast cancer cells. Br J Cancer 97:1090–1098 Toosi S, Naderi-Meshkin H, Kalalinia F, Pievandi MT, Hosseinkhani H, Bahrami AR et al (2017) Long bone mesenchymal stem cells (Lb-MSCs): clinically reliable cells for osteo-diseases. Cell Tissue Bank 18:489–500 Tsai L-K, Leng Y, Wang Z, Leeds P, Chuang D-M (2010) The mood stabilizers valproic acid and lithium enhance mesenchymal stem cell migration via distinct mechanisms. Neuropsychopharmacology 35:2225–2237 Vindis C, Cerretti DP, Daniel TO, Huynh-Do U (2003) EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote chemotaxis. J Cell Biol 162:661–671 Wahl EA, Schenck TL, Machens H-G, Balmayor ER (2016) VEGF released by deferoxamine preconditioned mesenchymal stem cells seeded on collagen-GAG substrates enhances neovascularization. Sci Rep 6:36879 Wang J, Tsirka SE (2005) Neuroprotection by inhibition of matrix metalloproteinases in a mouse model of intracerebral haemorrhage. Brain 128:1622–1633 Wang J, Wang Y, Wang S, Cai J, Shi J, Sui X et al (2015) Bone marrow-derived mesenchymal stem cell-secreted IL-8 promotes the angiogenesis and growth of colorectal cancer. Oncotarget 6:42825–42837 Waugh DJ, Wilson C (2008) The interleukin-8 pathway in cancer. Clin Cancer Res 14:6735–6741 Woo KJ, Lee T-J, Park J-W, Kwon TK (2006) Desferrioxamine, an iron chelator, enhances HIF-1α accumulation via cyclooxygenase-2 signaling pathway. Biochem Biophys Res Commun 343:8–14 Yagi H, Soto-Gutierrez A, Parekkadan B, Kitagawa Y, Tompkins RG, Kobayashi N, Yarmush ML (2010) Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transpl 19:667–679 Yamanegi K, Yamane J, Kobayashi K, Kato-Kogoe N, Ohyama H, Nakasho K et al (2012) Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma cells to Fas-and NK cell-mediated cell death. Int J Oncol 41:83–91 Yoo HI, Moon YH, Kim MS (2016) Effects of CoCl2 on multi-lineage differentiation of C3H/10T1/2 mesenchymal stem cells. Korean J Physiol Pharmacol 20:53–62 Zgouras D, Becker U, Loitsch S, Stein J (2004) Modulation of angiogenesis-related protein synthesis by valproic acid. Biochem Biophys Res Commun 316:693–697