مروری بر کاربرد سلول های بنیادی در طب نظامی

نوع مقاله : مروری

نویسندگان

1 مرکز تحقیقات بیوتکنولوژی کاربردی، دانشگاه علوم پزشکی بقیه الله (عج)، تهران، ایران

2 گروه علوم آزمایشگاهی، واحد بابل، دانشگاه آزاد اسلامی، بابل، ایران

3 گروه فارماکولوژی و توکسیکولوژی، دانشکده پزشکی، دانشگاه علوم پزشکی آجا، تهران، ایران

4 مرکز تحقیقات اپیدمیولوژی و پایش سرطان، دانشگاه علوم پزشکی آجا، تهران، ایران

چکیده

ماهیت جنگ‌ها در طول زمان با پیشرفت فناوری نظامی و تسلیحات جنگی همواره در حال تغییر است که منجربه الگوی متنوعی از آسیب­‌های بافتی شده است. پیشرفت در تجهیزات حفاظت فردی و زره بدن، انتقال سریع از میدان جنگ به مراکز درمانی، بهبود اقدامات احیا، کنترل خونریزی و مدیریت زخم به‌­طور قابل توجهی به بقای مجروحین جنگی کمک کرده است. با این حال مصدومین متحمل آسیب­‌های بافتی با درجات مختلف می­‌شوند که به موجب آن تحت درمان­‌های پیچیده و طولانی مدت قرار می­‌گیرند. افزایش بروز آسیب‌های ناشی از ادوات انفجاری در جنگ­‌های مدرن، درمان و بهبودی مصدومین را پیچیده‌تر کرده است که نیاز به شیوه‌­های نوین درمانی مبتنی بر سلول­‌های بنیادی را در طب نظامی برجسته می‌کند. سلول­های بنیادی از منابع مختلفی مانند مغز استخوان، بافت چربی، عضله اسکلتی، پوست، بافت ژله­‌وارتون و خون بندناف، جفت و مایع آمنیوتیک قابل حصول هستند و با قابلیت خودتجدیدشوندگی، تکثیر و تمایز به سلول‏‌های عملکردی بافت‌­های مختلف، فعالیت­‌های ضد التهابی، پاراکرینی و تعدیل‌کننده سیستم‌ایمنی، به‌عنوان یک رویکرد درمانی امیدبخش در رابطه با بسیاری از آسیب­‌های میدان نبرد و عوارض ناشی از آن­‌ها مورد توجه قرار گرفته‌­اند. تحقیقات اخیر در این زمینه، توسعه روش­‌هایی برای کاهش پیامدهای بحرانی در مواجهه با آسیب­‌های ناشی از جنگ را نشان می‌­دهد. در همین راستا، در این مطالعه علاوه‌بر تشریح مهمترین آسیب­‌های بافتی در جنگ­‌های مدرن، پیشرفت­‌های اخیر استفاده از سلول‌های بنیادی برای بازسازی بافت­‌های آسیب­‌دیده بررسی شده است.

کلیدواژه‌ها


1. Moniri K, Mirzakhani Silab R. Analytical review of S-300PMU-2 air defense system in the military doctrine of the Islamic Republic of Iran with a regional deterrence approach. Journal Strategic Studies of Public Policy. 2020;10(37):360-83. [In Persian] 2. Five thousand years’ history of humanity and passive defense. Available from: https://mahabad.umsu.ac.ir/uploads/tarikhche.pdf. 3. Manring MM, Hawk A, Calhoun JH, Andersen RC. Treatment of war wounds: a historical review. Clinical Orthopaedics and Related Research®. 2009;467(8):2168-91. doi:10.1007/s11999-009-0738-5 4. Ude CC, Miskon A, Idrus RB, Abu Bakar MB. Application of stem cells in tissue engineering for defense medicine. Military Medical Research. 2018;5(1):7. doi:10.1186/s40779-018-0154-9 5. Saha B, Kumar HK, Borgohain MP, Thummer RP. Prospective applications of induced pluripotent stem cells in military medicine. Medical Journal Armed Forces India. 2018;74(4):313-20. doi:10.1016/j.mjafi.2018.03.005 6. Öztürk S, Elçin AE, Koca A, Elçin YM. Therapeutic applications of stem cells and extracellular vesicles in emergency care: futuristic perspectives. Stem Cell Reviews and Reports. 2021;17(2):390-410. doi:10.1007/s12015-020-10029-2 7. DeChellis DM, Cortazzo MH. Regenerative medicine in the field of pain medicine: Prolotherapy, platelet-rich plasma therapy, and stem cell therapy—Theory and evidence. Techniques in Regional Anesthesia and Pain Management. 2011;15(2):74-80. doi:10.1053/j.trap.2011.05.002 8. Christopherson GT, Nesti LJ. Stem cell applications in military medicine. Stem Cell Research & Therapy. 2011;2(5):40. doi:10.1186/scrt81 9. Kolios G, Moodley Y. Introduction to stem cells and regenerative medicine. Respiration. 2013;85:3-10. doi:10.1159/000345615 10. Ramalho-Santos M, Willenbring H. On the origin of the term “stem cell”. Cell stem cell. 2007;1(1):35-8. doi:10.1016/j.stem.2007.05.013 11. Sell S, editor. Stem cells handbook. Springer Science & Business Media; 2013. doi:10.1007/978-1-4614-7696-2 12. Silva LB, Neto AP, Pacheco RG, Júnior SA, de Menezes RF, Carneiro VS, et al. The promising applications of stem cells in the oral region: literature review. The Open Dentistry Journal. 2016;10:227. doi:10.2174/1874210601610010227 13. Caplan AI. Mesenchymal stem cells. Journal of orthopaedic research. 1991;9(5):641-50. doi:10.1002/jor.1100090504 14. Henig I, Zuckerman T. Hematopoietic stem cell transplantation—50 years of evolution and future perspectives. Rambam Maimonides Medical Journal. 2014;5(4):e0028. doi:10.5041/RMMJ.10162 15. Armstrong L, Lako M, Buckley N, Lappin TR, Murphy MJ, Nolta JA, et al. Our top 10 developments in stem cell biology over the last 30 years. Stem Cells. 2012;30(1):2-9. doi:10.1002/stem.1007 16. Becker AJ, Mc CE, Till JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature. 1963;197(4866):452–4. doi:10.1038/197452a0 17. ASBMT and CBMTG Release Choosing Wisely BMT Recommendations. Biology of Blood and Marrow Transplantation. 2018;24(4):880-1. doi:10.1016/j.bbmt.2018.03.020 18. Rippon HJ, Bishop AE. Embryonic stem cells. Cell Proliferation. 2004;37(1):23-34. doi:10.1111/j.1365-2184.2004.00298.x 19. Aleckovic M, Simón C. Is teratoma formation in stem cell research a characterization tool or a window to developmental biology?. Reproductive Biomedicine Online. 2008;17(2):270-80. doi:10.1016/S1472-6483(10)60206-4 20. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145-7. doi:10.1126/science.282.5391.1145 21. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663-76. doi:10.1016/j.cell.2006.07.024 22. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861-72. doi:10.1016/j.cell.2007.11.019 23. Colman A. Profile of John Gurdon and Shinya Yamanaka, 2012 Nobel laureates in medicine or physiology. Proceedings of the National Academy of Sciences. 2013;110(15):5740-1. doi:10.1073/pnas.1221823110 24. Verma A, Verma N. Induced pluripotent stem cells and promises of neuroregenerative medicine. Neurology India. 2011;59(4):555-7. doi:10.4103/0028-3886.84337 25. Kimbrel EA, Lanza R. Current status of pluripotent stem cells: moving the first therapies to the clinic. Nature Reviews Drug Discovery. 2015;14(10):681-92. doi:10.1038/nrd4738 26. Nguyen QD, Kruger EF, Kim AJ, Lashkari MH, Lashkari K. Combat eye trauma: intraocular foreign body injuries during the Iran-Iraq war (1980–1988). International Ophthalmology Clinics. 2002;42(3):167-77. doi:10.1097/00004397-200207000-00018 27. Weichel ED, Colyer MH. Combat ocular trauma and systemic injury. Current Opinion in Ophthalmology. 2008;19(6):519-25. doi:10.1097/ICU.0b013e3283140e98 28. Scott R. The injured eye. Philosophical Transactions of the Royal Society B: Biological Sciences. 2011;366(1562):251-60. doi:10.1098/rstb.2010.0234 29. Kokkinaki M, Sahibzada N, Golestaneh N. Human induced pluripotent stem‐derived retinal pigment epithelium (RPE) cells exhibit ion transport, membrane potential, polarized vascular endothelial growth factor secretion, and gene expression pattern similar to native RPE. Stem Cells. 2011;29(5):825-35. doi:10.1002/stem.635 30. Lamba DA, McUsic A, Hirata RK, Wang PR, Russell D, Reh TA. Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells. PloS One. 2010;5(1):e8763. doi:10.1371/journal.pone.0008763 31. Parameswaran S, Balasubramanian S, Babai N, Qiu F, Eudy JD, Thoreson WB, et al. Induced pluripotent stem cells generate both retinal ganglion cells and photoreceptors: Therapeutic implications in degenerative changes in glaucoma and age‐related macular degeneration. Stem Cells. 2010;28(4):695-703. doi:10.1002/stem.320 32. Mandai M, Watanabe A, Kurimoto Y, Hirami Y, Morinaga C, Daimon T, et al. Autologous induced stem-cell–derived retinal cells for macular degeneration. New England Journal of Medicine. 2017;376(11):1038-46. doi:10.1056/NEJMoa1608368 33. Jahed V, Daryabari SH, Jadidi K, Aghamollaei H. Application of Cell Therapy for Treatment of Chemical and Traumatic Corneal Injuries. Journal of Military Medicine. 2021;23(6):518-28. doi:10.30491/JMM.23.6.518 34. Aghamollaei H, Hashemian H, Safabakhsh H, Halabian R, Baghersad M, Jadidi K. Safety of grafting acellular human corneal lenticule seeded with Wharton's Jelly-Derived Mesenchymal Stem Cells in an experimental animal model. Experimental Eye Research. 2021;205:108451. doi:10.1016/j.exer.2021.108451 35. Ghazaleh AH, Khosravi Z. Mechanism and Type of Ear Injuries among Iranian Veterans during Iraq-Iran War. Canon Journal of Medicine. 2019;1(2):70-2. doi:10.30477/CJM.2019.91742 36. Edge AS, Chen ZY. Hair cell regeneration. Current Opinion in Neurobiology. 2008;18(4):377-82. doi:10.1016/j.conb.2008.10.001 37. Astaraki P, Falahi E, Narimani S, Ahadi M. Evaluating of frequency of auditory system damage in the wounded of explosive remnants of war in Ilam. Scientific Journal of Forensic Medicine. 2008;14(2):77-81. 38. Niknazar S, Simani L, Peyvandi H, Peyvandi AA. Therapeutic potential of cell therapy in the repair of hair cells and spiral ganglion neurons. Tehran University Medical Journal TUMS Publications. 2019;77(8):469-75. 39. Huang YB, Ma R, Yang JM, Han Z, Cong N, Gao Z, et al. Cell proliferation during hair cell regeneration induced by Math1 in vestibular epithelia in vitro. Neural Regeneration Research. 2018;13(3):497-501. doi:10.4103/1673-5374.228734 40. Johnson KR, Gagnon LH, Tian C, Longo-Guess CM, Low BE, Wiles MV, et al. Deletion of a long-range Dlx5 enhancer disrupts inner ear development in mice. Genetics. 2018;208(3):1165-79. doi:10.1534/genetics.117.300447 41. Lee MY, Hackelberg S, Green KL, Lunghamer KG, Kurioka T, Loomis BR, et al. Survival of human embryonic stem cells implanted in the guinea pig auditory epithelium. Scientific Reports. 2017;7(1):46058. doi:10.1038/srep46058 42. Hyakumura T, McDougall S, Finch S, Needham K, Dottori M, Nayagam BA. Organotypic cocultures of human pluripotent stem cell derived-neurons with mammalian inner ear hair cells and cochlear nucleus slices. Stem Cells International. 2019;2019:8419493. doi:10.1155/2019/8419493 43. Chang HT, Heuer RA, Oleksijew AM, Coots KS, Roque CB, Nella KT, et al. An engineered three-dimensional stem cell niche in the inner ear by applying a nanofibrillar cellulose hydrogel with a sustained-release neurotrophic factor delivery system. Acta Biomaterialia. 2020;108:111-27. doi:10.1016/j.actbio.2020.03.007 44. Ohnishi H, Skerleva D, Kitajiri SI, Sakamoto T, Yamamoto N, Ito J, Nakagawa T. Limited hair cell induction from human induced pluripotent stem cells using a simple stepwise method. Neuroscience Letters. 2015;599:49-54. doi:10.1016/j.neulet.2015.05.032 45. Lahlou H, Nivet E, Lopez-Juarez A, Fontbonne A, Assou S, Zine A. Enriched differentiation of human otic sensory progenitor cells derived from induced pluripotent stem cells. Frontiers in Molecular Neuroscience. 2018;11:452. doi:10.3389/fnmol.2018.00452 46. Desmoulin GT, Dionne JP. Blast-induced neurotrauma: surrogate use, loading mechanisms, and cellular responses. Journal of Trauma and Acute Care Surgery. 2009;67(5):1113-22. doi:10.1097/TA.0b013e3181bb8e84 47. Przekwas A, Somayaji MR, Gupta RK. Synaptic mechanisms of blast-induced brain injury. Frontiers in Neurology. 2016;7:2. doi:10.3389/fneur.2016.0000 48. Houlé JD, Reier PJ. Transplantation of fetal spinal cord tissue into the chronically injured adult rat spinal cord. Journal of Comparative Neurology. 1988;269(4):535-47. doi:10.1002/cne.902690406 49. Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, et al. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell. 2012;150(6):1264-73. doi:10.1016/j.cell.2012.08.020 50. Okubo T, Nagoshi N, Kohyama J, Tsuji O, Shinozaki M, Shibata S, et al. Treatment with a gamma-secretase inhibitor promotes functional recovery in human iPSC-derived transplants for chronic spinal cord injury. Stem Cell Reports. 2018;11(6):1416-32. doi:10.1016/j.stemcr.2018.10.022 51. Hanatani T, Takasu N. CiRA iPSC seed stocks (CiRA's iPSC stock project). Stem Cell Research. 2021;50:102033. doi:10.1016/j.scr.2020.102033 52. Deuse T, Hu X, Gravina A, Wang D, Tediashvili G, De C, et al. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nature Biotechnology. 2019;37(3):252-8. doi:10.1038/s41587-019-0016-3 53. Uemura T, Takamatsu K, Ikeda M, Okada M, Kazuki K, Ikada Y, et al. Transplantation of induced pluripotent stem cell-derived neurospheres for peripheral nerve repair. Biochemical and Biophysical Research Communications. 2012;419(1):130-5. doi:10.1016/j.bbrc.2012.01.154 54. Ahuja CS, Nori S, Tetreault L, Wilson J, Kwon B, Harrop J, et al. Traumatic spinal cord injury—repair and regeneration. Neurosurgery. 2017;80(3S):S9-22. doi:10.1093/neuros/nyw080 55. Liu AM, Chen BL, Yu LT, Liu T, Shi LL, Yu PP, et al. Human adipose tissue-and umbilical cord-derived stem cells: which is a better alternative to treat spinal cord injury?. Neural Regeneration Research. 2020;15(12):2306-17. doi:10.4103/1673-5374.284997 56. Hofer HR, Tuan RS. Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies. Stem Cell Research & Therapy. 2016;7(1):131. doi:10.1186/s13287-016-0394-0 57. Zhao Y, Gibb SL, Zhao J, Moore AN, Hylin MJ, Menge T, et al. Wnt3a, a protein secreted by mesenchymal stem cells is neuroprotective and promotes neurocognitive recovery following traumatic brain injury. Stem Cells. 2016;34(5):1263-72. doi:10.1002/stem.2310 58. Morita T, Sasaki M, Kataoka-Sasaki Y, Nakazaki M, Nagahama H, Oka S, et al. Intravenous infusion of mesenchymal stem cells promotes functional recovery in a model of chronic spinal cord injury. Neuroscience. 2016;335:221-31. doi:10.1016/j.neuroscience.2016.08.037 59. Branda CS, Dymecki SM. Talking about a revolution: The impact of site-specific recombinases on genetic analyses in mice. Developmental Cell. 2004;6(1):7-28. doi:10.1016/S1534-5807(03)00399-X 60. Zamboni M, Llorens-Bobadilla E, Magnusson JP, Frisén J. A widespread neurogenic potential of neocortical astrocytes is induced by injury. Cell Stem Cell. 2020;27(4):605-17. doi:10.1016/j.stem.2020.07.006 61. Guo Z, Zhang L, Wu Z, Chen Y, Wang F, Chen G. In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer’s disease model. Cell Stem Cell. 2014;14(2):188-202. doi:10.1016/j.stem.2013.12.001 62. Li X, Floriddia EM, Toskas K, Chalfouh C, Honore A, Aumont A, et al. FoxJ1 regulates spinal cord development and is required for the maintenance of spinal cord stem cell potential. Experimental Cell Research. 2018;368(1):84-100. doi:10.1016/j.yexcr.2018.04.017 63. Llorens-Bobadilla E, Chell JM, Le Merre P, Wu Y, Zamboni M, Bergenstråhle J, et al. A latent lineage potential in resident neural stem cells enables spinal cord repair. Science. 2020;370(6512):eabb8795. doi:10.1126/science.abb8795 64. Murray CK, Hsu JR, Solomkin JS, Keeling JJ, Andersen RC, Ficke JR, et al. Prevention and management of infections associated with combat-related extremity injuries. Journal of Trauma and Acute Care Surgery. 2008;64(3):S239-51. doi:10.1097/TA.0b013e318163cd14 65. Schoenfeld AJ, Belmont PJ. Traumatic combat injuries. In: Cameron KL, Owens BD, eds. Musculoskeletal injuries in the military. Springer; 2016. doi:10.1007/978-1-4939-2984-9_2 66. Casey K, Demers P, Deben S, Nelles ME, Weiss JS. Outcomes after long-term follow-up of combat-related extremity injuries in a multidisciplinary limb salvage clinic. Annals of Vascular Surgery. 2015;29(3):496-501. doi:10.1016/j.avsg.2014.09.035 67. Al Faqeh H, Hamdan BM, Chen HC, Aminuddin BS, Ruszymah BH. The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model. Experimental gerontology. 2012;47(6):458-64. doi.org/10.1016/j.exger.2012.03.018 68. Ude CC, Sulaiman SB, Min-Hwei N, Hui-Cheng C, Ahmad J, Yahaya NM, et al. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model. PLoS One. 2014;9(6):e98770. doi:10.1371/journal.pone.0098770 69. Ude CC, Ng MH, Chen CH, Htwe O, Amaramalar NS, Hassan S, et al. Improved functional assessment of osteoarthritic knee joint after chondrogenically induced cell treatment. Osteoarthritis and cartilage. 2015;23(8):1294-306. doi:10.1016/j.joca.2015.04.003 70. Holden C. Rebuilding the Injured Warrior. Science. 2008;320(5875):437. doi:10.1126/science.320.5875.437a 71. Majumdar MK, Thiede MA, Mosca JD, Moorman M, Gerson SL. Phenotypic and functional comparison of cultures of marrow‐derived mesenchymal stem cells (MSCs) and stromal cells. Journal of Cellular Physiology. 1998;176(1):57-66. doi:10.1002/(SICI)1097-4652(199807)176:1<57::AID-JCP7>3.0.CO;2-7 72. Pollak AN, Ficke JR, Injuries III EW. Extremity war injuries: challenges in definitive reconstruction. JAAOS-Journal of the American Academy of Orthopaedic Surgeons. 2008;16(11):628-34. doi:10.5435/00124635-200811000-00003 73. Baksh D, Yao R, Tuan RS. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells. 2007;25(6):1384-92. doi:10.1634/stemcells.2006-0709 74. Sakurai H, Sakaguchi Y, Shoji E, Nishino T, Maki I, Sakai H, et al. In vitro modeling of paraxial mesodermal progenitors derived from induced pluripotent stem cells. PloS One. 2012;7(10):e47078. doi:10.1371/journal.pone.0047078 75. Jeon OH, Panicker LM, Lu Q, Chae JJ, Feldman RA, Elisseeff JH. Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials. Scientific reports. 2016;6(1):26761. doi:10.1038/srep26761 76. Yang L, Wang Q, Peng L, Yue H, Zhang Z. Vascularization of repaired limb bone defects using chitosan-β-tricalcium phosphate composite as a tissue engineering bone scaffold. Molecular Medicine Reports. 2015;12(2):2343-7. doi:10.3892/mmr.2015.3653 77. Bueno EM, Glowacki J. Cell-free and cell-based approaches for bone regeneration. Nature Reviews Rheumatology. 2009;5(12):685-97. doi:10.1038/nrrheum.2009.228 78. Vijayavenkataraman S, Lu WF, Fuh JY. 3D bioprinting of skin: a state-of-the-art review on modelling, materials, and processes. Biofabrication. 2016;8(3):032001. doi:10.1088/1758-5090/8/3/032001 79. Mayet N, Choonara YE, Kumar P, Tomar LK, Tyagi C, Du Toit LC, et al. A comprehensive review of advanced biopolymeric wound healing systems. Journal of Pharmaceutical Sciences. 2014;103(8):2211-30. doi:10.1002/jps.24068 80. Shi C, Zhu Y, Su Y, Cheng T. Stem cells and their applications in skin-cell therapy. TRENDS in Biotechnology. 2006;24(1):48-52. doi:10.1016/j.tibtech.2005.11.003 81. Shpichka A, Butnaru D, Bezrukov EA, Sukhanov RB, Atala A, Burdukovskii V, et al. Skin tissue regeneration for burn injury. Stem Cell Research & Therapy. 2019;10(1):94. doi:10.1186/s13287-019-1203-3 82. Ohta S, Imaizumi Y, Okada Y, Akamatsu W, Kuwahara R, Ohyama M, et al. Generation of human melanocytes from induced pluripotent stem cells. PloS One. 2011;6(1):e16182. doi:10.1371/journal.pone.0016182 83. Hosaka C, Kunisada M, Koyanagi‐Aoi M, Masaki T, Takemori C, Taniguchi‐Ikeda M, et al. Induced pluripotent stem cell‐derived melanocyte precursor cells undergoing differentiation into melanocytes. Pigment Cell & Melanoma Research. 2019;32(5):623-33. doi:10.1111/pcmr.12779 84. Itoh M, Kiuru M, Cairo MS, Christiano AM. Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells. Proceedings of the National Academy of Sciences. 2011;108(21):8797-802. doi:10.1073/pnas.1100332108 85. Itoh M, Umegaki-Arao N, Guo Z, Liu L, Higgins CA, Christiano AM. Generation of 3D skin equivalents fully reconstituted from human induced pluripotent stem cells (iPSCs). PloS One. 2013;8(10):e77673. doi:10.1371/journal.pone.0077673 86. Hu MS, Borrelli MR, Lorenz HP, Longaker MT, Wan DC. Mesenchymal stromal cells and cutaneous wound healing: a comprehensive review of the background, role, and therapeutic potential. Stem Cells International. 2018;2018:6901983. doi:10.1155/2018/6901983 87. Chiossone L, Conte R, Spaggiari GM, Serra M, Romei C, Bellora F, et al. Mesenchymal stromal cells induce peculiar alternatively activated macrophages capable of dampening both innate and adaptive immune responses. Stem Cells. 2016;34(7):1909-21. doi:10.1002/stem.2369 88. Zhao MM, Cui JZ, Cui Y, Li R, Tian YX, Song SX, et al. Therapeutic effect of exogenous bone marrow derived mesenchymal stem cell transplantation on silicosis via paracrine mechanisms in rats. Molecular Medicine Reports. 2013;8(3):741-6. doi:10.3892/mmr.2013.1580 89. Ellis S, Lin EJ, Tartar D. Immunology of wound healing. Current Dermatology Reports. 2018;7(4):350-8. doi:10.1007/s13671-018-0234-9 90. Qiu X, Liu J, Zheng C, Su Y, Bao L, Zhu B, et al. Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis. Cell Proliferation. 2020;53(8):e12830. doi:10.1111/cpr.12830 91. Zhang W, Bai X, Zhao B, Li Y, Zhang Y, Li Z, et al. Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway. Experimental Cell Research. 2018;370(2):333-42. doi:10.1016/j.yexcr.2018.06.035 92. Rustad KC, Wong VW, Sorkin M, Glotzbach JP, Major MR, Rajadas J, et al. Enhancement of mesenchymal stem cell angiogenic capacity and stemness by a biomimetic hydrogel scaffold. Biomaterials. 2012;33(1):80-90. doi:10.1016/j.biomaterials.2011.09.041 93. Cooney DS, Wimmers EG, Ibrahim Z, Grahammer J, Christensen JM, Brat GA, et al. Mesenchymal stem cells enhance nerve regeneration in a rat sciatic nerve repair and hindlimb transplant model. Scientific Reports. 2016;6(1):31306. doi:10.1038/srep31306 94. William Saletan. Rearming America: The military's plan to regrow body parts. Available: http://www.slate.com/articles/health_and_science/human_nature/2008/04/rearming_america.html. Accessed 21 Dec 2016. 95. Kime P. Bio-engineering skin to treat severe burns. Available: http://www.militarytimes.com/story/military/benefits/health-care/2015/10/11/bioengineering-skin-treat-severe-burns/73511584/. Accessed 21 Dec 2016.