The potential of mesenchymal stem‐cell secretome for regeneration of intervertebral disc: A review article

https://doi.org/10.22146/ijbiotech.63318

Romaniyanto Romaniyanto(1*), Cita Rosita Sigit Prakoeswa(2), Damayanti Tinduh(3), Hari Basuki Notobroto(4), Fedik Abdul Rantam(5), Dwikora Novembri Utomo(6), Heri Suroto(7), Ferdiansyah Ferdiansyah(8)

(1) Doctoral Program, Faculty of Medicine, Airlangga University, Surabaya, Jawa Timur 60132; Department of Orthopedic and Traumatology, Faculty of Medicine, Prof. Dr. R. Soeharso Orthopaedic Hospital, Universitas Sebelas Maret, Surakarta, Jawa Tengah 57126
(2) Department of Dermatology and Venereology, Faculty of Medicine, Airlangga University, Surabaya, Jawa Timur 60132; Dr. Soetomo General Academic Hospital, Surabaya, Jawa Timur 60286
(3) Dr. Soetomo General Academic Hospital, Surabaya, Jawa Timur 60286; Dr. Soetomo General Academic Hospital, Surabaya, Jawa Timur 60286
(4) Dr. Soetomo General Academic Hospital, Surabaya, Jawa Timur 60286
(5) Dr. Soetomo General Academic Hospital, Surabaya, Jawa Timur 60286
(6) Dr. Soetomo General Academic Hospital, Surabaya, Jawa Timur 60286; Department of Orthopedic and Traumatology, Faculty of Medicine, Faculty of Medicine, Airlangga University, Surabaya, Jawa Timur 60132
(7) Dr. Soetomo General Academic Hospital, Surabaya, Jawa Timur 60286; Department of Orthopedic and Traumatology, Faculty of Medicine, Faculty of Medicine, Airlangga University, Surabaya, Jawa Timur 60132
(8) Dr. Soetomo General Academic Hospital, Surabaya, Jawa Timur 60286; Department of Orthopedic and Traumatology, Faculty of Medicine, Faculty of Medicine, Airlangga University, Surabaya, Jawa Timur 60132
(*) Corresponding Author

Abstract


Low back pain is a crucial public health problem that is commonly associated with intervertebral disc de‐ generation and has vast socio‐economic impact worldwide. Current treatments for disc degeneration are conservative, non‐surgical, or surgical interventions, and there is no current clinical therapy aimed at directly reversing the degeneration. Given the limited capacity of intervertebral disc (IVD) cells to self‐repair, treatment aiming to regenerate IVDs is a topic of interest and mesenchymal stem cells (MSCs) have been identified as having potential in this regeneration. Recent studies have revealed that the benefits of MSC therapy could result from the molecules the cells secrete and that play principal roles in regulating essential biologic processes, rather than from the implanted cells themselves. Therefore, the objective of this study is to review the potential use of the MSC secretome to regenerate IVDs. Current evidence shows that the secretome may regenerate IVDs by modulating the gene expressions of nucleus pulposus cells (upregulation of keratin 19 and downregulation of matrix metalloproteinase 12 and matrix Gla protein) and stimulating IVD progenitor cells to repair the degenerated disc.

Keywords


Intervertebral disc degeneration; low back pain; mesenchymal stem cells; regenerative properties; secretome

Full Text:

PDF


References

Ab Kadir R, Zainal Ariffin SH, Megat Abdul Wahab R, Kermani S, Senafi S. 2012. Characterization of mononucleated human peripheral blood cells. Sci World J. 2012:1–8. doi:10.1100/2012/843843.

Abumaree M, Al Jumah M, Pace RA, Kalionis B. 2012. Immunosuppressive Properties of Mesenchymal Stem Cells. Stem Cell Reviews and Reports 8(2):375–392. doi:10.1007/s12015­011­9312­0.

Allickson JG. 2011. Recent Studies Assessing the Proliferative Capability of a Novel Adult Stem Cell Identified in Menstrual Blood. Open Stem Cell J. 3(1):4–10. doi:10.2174/1876893801103010004.

Allon AA, Aurouer N, Yoo BB, Liebenberg EC, Buser Z, Lotz JC. 2010. Structured coculture of stem cells and disc cells prevent disc degeneration in a rat model. Spine J. 10(12):1089–1097. doi:10.1016/j.spinee.2010.09.014.

Alsalameh S, Amin R, Gemba T, Lotz M. 2004. Identification of Mesenchymal Progenitor Cells in Normal and Osteoarthritic Human Articular Cartilage. Arthritis Rheumatol. 50(5):1522–1532. doi:10.1002/art.20269.

Appaix F. 2014. Brain mesenchymal stem cells: The other stem cells of the brain? World J Stem Cells. 6(2):134. doi:10.4252/wjsc.v6.i2.134.

Bach FC, Willems N, Penning LC, Ito K, Meij BP, Tryfonidou MA. 2014. Potential regenerative treatment strategies for intervertebral disc degeneration in dogs. BMC Vet Res. 10. doi:10.1186/1746­6148­10­3.

Bachmeier BE, Nerlich AG, Weiler C, Paesold G, Jochum M, Boos N. 2007. Analysis of tissue distribution of TNF­α, TNF­α­receptors, and the activating TNF­α– converting enzyme suggests activation of the TNF­α? System in the aging intervertebral disc. Ann N Y Acad Sci. 1096:44–54. doi:10.1196/annals.1397.069.

Baglio SR, Pegtel DM, Baldini N. 2012. Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell­free therapy. Front Physiol. 3 SEP(September):1–11. doi:10.3389/fphys.2012.00359.

Balasubramanian S, Thej C, Venugopal P, Priya N, Zakaria Z, Sundarraj S, Majumdar AS. 2013. Higher propensity of Wharton’s jelly derived mesenchymal stromal cells towards neuronal lineage in comparison to those derived from adipose and bone marrow. Cell Biol Int. 37(5):507–515. doi:10.1002/cbin.10056.

Bartosh TJ, Ylöstalo JH, Mohammadipoor A, Bazhanov N, Coble K, Claypool K, Lee RH, Choi H, Prockop DJ. 2010. Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Proc Natl Acad Sci USA. 107(31):13724–13729. doi:10.1073/pnas.1008117107.

Basu J, Ludlow JW. 2016. Exosomes for repair, regeneration and rejuvenation. Expert Opin Biol Ther. 16(4):489–506. doi:10.1517/14712598.2016.1131976.

Beer L, Mildner M, Ankersmit HJ. 2017. Cell secretome based drug substances in regenerative medicine: When regulatory affairs meet basic science. Ann Transl Med. 5(7):5–7. doi:10.21037/atm.2017.03.50.

Ben­Ami E, Berrih­Aknin S, Miller A. 2011. Mesenchymal stem cells as an immunomodulatory therapeutic strategy for autoimmune diseases. doi:10.1016/j.autrev.2011.01.005.

Bendtsen M, Bunger C, Colombier P, Le Visage C, Roberts S, Sakai D, Urban JP. 2016. Biological challenges for regeneration of the degenerated disc using cellular therapies. Acta Orthop. 87:39–46. doi:10.1080/17453674.2017.1297916.

Bogduk N, Windsor M, Inglis A. 1988. The innervation of the cervical intervertebral discs. Spine. 13(1):2–8. doi:10.1097/00007632­198801000­00002.

Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG. 2002. Classification of age­related changes in lumbar intervertebral discs: 2002 Volvo award in basic science. Spine 27(23):2631–2644. doi:10.1097/00007632­200212010­00002.

Brisby H, Papadimitriou N, Brantsing C, Bergh P, Lindahl A, Barreto Henriksson H. 2013. The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: A descriptive study in humans. Stem Cells Dev. 22(5):804–814. doi:10.1089/scd.2012.0179.

Cai J, Li W, Su H, Qin D, Yang J, Zhu F, Xu J, He W, Guo X, Labuda K, et al. 2010. Generation of human induced pluripotent stem cells from umbilical cord matrix and amniotic membrane mesenchymal cells. J Biol Chem. 285(15):11227–11234. doi:10.1074/jbc.M109.086389.

Caplan AI, Dennis JE. 2006. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 98(5):1076–1084. doi:10.1002/jcb.20886.

Caseiro AR, Pereira T, Ivanova G, Luís AL, Maurício AC. 2016. Neuromuscular Regeneration: Perspective on the Application of Mesenchymal Stem Cells and Their Secretion Products. Stem Cells Int. 2016. doi:10.1155/2016/9756973.

Cheung KM, Karppinen J, Chan D, Ho DW, Song YQ, Sham P, Cheah KS, Leong JC, Luk KD. 2009. Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty­three individuals. Spine. 34(9):934–940. doi:10.1097/BRS.0b013e3181a01b3f.

Clouet J, Fusellier M, Camus A, Le Visage C, Guicheux J. 2019. Intervertebral disc regeneration: From cell therapy to the development of novel bioinspired endogenous repair strategies. Adv Drug Delivery Rev. 146:306–324. doi:10.1016/j.addr.2018.04.017.

Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, Viltono L, Tetta C, Camussi G. 2010. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS ONE. 5(7). doi:10.1371/journal.pone.0011803.

Comella K, Silbert R, Parlo M. 2017. Effects of the intradiscal implantation of stromal vascular fraction plus platelet rich plasma in patients with degenerative disc disease. J Transl Med. 15(1):12. doi:10.1186/s12967­016­1109­0.

Comoli P, Ginevri F, MacCario R, Avanzini MA, Marconi M, Groff A, Cometa A, Cioni M, Porretti L, Barberi W, Frassoni F, Locatelli F. 2008. Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation. Nephrol Dial Transplant. 23(4):1196–1202. doi:10.1093/ndt/gfm740.

Croitoru­Lamoury J, Lamoury FM, Caristo M, Suzuki K, Walker D, Takikawa O, Taylor R, Brew BJ. 2011. Interferon­γ regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2,3 dioxygenase (IDO). PLoS ONE. 6(2). doi:10.1371/journal.pone.0014698.

Das R, Jahr H, van Osch GJ, Farrell E. 2010. The role of hypoxia in bone marrow­derived mesenchymal stem cells: considerations for regenerative medicine approaches. Tissue Eng. Part B, Rev. 16(2):159–168. doi:10.1089/ten.teb.2009.0296.

Deyo RA, Bass JE. 1989. Lifestyle and low­back pain the influence of smoking and obesity. Spine 14(5):501– 506. doi:10.1097/00007632­198905000­00005.

Di G, Du X, Qi X, Zhao X, Duan H, Li S, Xie L, Zhou Q. 2017. Mesenchymal stem cells promote diabetic corneal epithelial wound healing through TSG­ 6­dependent stem cell activation and macrophage switch. Invest Ophthalmol Visual Sci. 58(10):4064– 4074. doi:10.1167/iovs.17­21506.

Doeppner TR, Herz J, Görgens A, Schlechter J, Ludwig AK, Radtke S, de Miroschedji K, Horn PA, Giebel B, Hermann DM. 2015. Extracellular Vesicles Improve Post­Stroke Neuroregeneration and Prevent Postischemic Immunosuppression. Stem Cells Transl Med. 4(10):1131–1143. doi:10.5966/sctm.2015­0078.

Dominici M, Le Blanc K, Mueller I, Slaper­Cortenbach I, Marini FC, Krause DS, Deans RJ, Keating A, Prockop DJ, Horwitz EM. 2006. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 8(4):315–317. doi:10.1080/14653240600855905.

Driscoll T, Jacklyn G, Orchard J, Passmore E, Vos T, Freedman G, Lim S, Punnett L. 2014. The global burden of occupationally related low back pain: Estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis. 73(6):975–981. doi:10.1136/annrheumdis­2013­204631.

Eiró N, Sendon­Lago J, Seoane S, Bermúdez MA, Lamelas ML, Garcia­Caballero T, Schneider J, PerezFernandez R, Vizoso FJ. 2014. Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells. Oncotarget. 5(21):10692–10708. doi:10.18632/oncotarget.2530.

Ejtehadifar M, Shamsasenjan K, Movassaghpour A, Akbarzadehlaleh P, Dehdilani N, Abbasi P, Molaeipour Z, Saleh M. 2015. The effect of hypoxia on mesenchymal stem cell biology. Adv Pharm Bull. 5(2):141– 149. doi:10.15171/apb.2015.021.

Eleuteri S, Fierabracci A. 2019. Insights into the secretome of mesenchymal stem cells and its potential applications. Int J Mol Sci. 20(18). doi:10.3390/ijms20184597.

Erwin WM. 2010. The enigma that is the nucleus pulposus cell: The search goes on. Arthritis Research and Therapy 12(3). doi:10.1186/ar3001. Erwin WM, Hood KE. 2014. The cellular and molecular biology of the intervertebral disc: A clinician’s primer. J Can Chiropr Assoc. 58(3):246–257.

Ferreira JR, Teixeira GQ, Santos SG, Barbosa MA, Almeida­Porada G, Gonçalves RM. 2018. Mesenchymal stromal cell secretome: Influencing therapeutic potential by cellular pre­conditioning. Front Immunol. 9. doi:10.3389/fimmu.2018.02837.

Fierabracci A, Del Fattore A, Luciano R, Muraca M, Teti A, Muraca M. 2015. Recent advances in mesenchymal stem cell immunomodulation: The role of microvesicles. Cell Transplant. 24(2):133–149. doi:10.3727/096368913X675728.

Fisher­Shoval Y, Barhum Y, Sadan O, Yust­Katz S, BenZur T, Lev N, Benkler C, Hod M, Melamed E, Offen D. 2012. Transplantation of placenta­derived mesenchymal stem cells in the EAE mouse model of MS. J Mol Neurosci. 48(1):176–184. doi:10.1007/s12031­ 012­9805­6.

Fornaro M, Giovannelli A, Foggetti A, Muratori L, Geuna S, Novajra G, Perroteau I. 2020. Role of neurotrophic factors in enhancing linear axonal growth of ganglionic sensory neurons in vitro. Neural Regener Res. 15(9):1732–1739. doi:10.4103/1673­5374.276338.

Freeman BJ, Kuliwaba JS, Jones CF, Shu CC, Colloca CJ, Zarrinkalam MR, Mulaibrahimovic A, Gronthos S, Zannettino AC, Howell S. 2016. Allogeneic Mesenchymal Precursor Cells Promote Healing in Postero­lateral Annular Lesions and Improve Indices of Lumbar Intervertebral Disc Degeneration in an Ovine Model. Spine. 41(17):1331–1339. doi:10.1097/BRS.0000000000001528.

Freemont AJ. 2009. The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. doi:10.1093/rheumatology/ken396.

Freemont AJ, Watkins A, Le Maitre C, Baird P, Jeziorska M, Knight MT, Ross ER, O’Brien JP, Hoyland JA. 2002. Nerve growth factor expression and innervation of the painful intervertebral disc. J Pathol. 197(3):286–292. doi:10.1002/path.1108.

Gieseke F, Böhringer J, Bussolari R, Dominici M, Handgretinger R, Müller I. 2010. Human multipotent mesenchymal stromal cells use galectin­1 to inhibit immune effector cells. Blood. 116(19):3770–3779. doi:10.1182/blood­2010­02­270777.

Gieseke F, Kruchen A, Tzaribachev N, Bentzien F, Do­minici M, Müller I. 2013. Proinflammatory stimuli induce galectin­9 in human mesenchymal stromal cells to suppress T­cell proliferation. Eur J Immunol. 43(10):2741–2749. doi:10.1002/eji.201343335.

Grote K, Petri M, Liu C, Jehn P, Spalthoff S, Kokemüller H, Luchtefeld M, Tschernig T, Krettek C, Haasper C, Jagodzinski M. 2013. Toll­like receptor 2/6­ dependent stimulation of mesenchymal stem cells promotes angiogenesis by paracrine factors. Eur Cells Mater. 26:66–79. doi:10.22203/eCM.v026a05.

Gruber HE, Ingram JA, Hoelscher G, Zinchenko N, James HJ, Hanley EN. 2008. Brain­derived neurotrophic factor and its receptor in the human and the sand rat intervertebral disc. Arthritis Res Ther. 10(4). doi:10.1186/ar2456.

Hayflick L, Moorhead PS. 1961. The serial cultivation of human diploid cell strains. Exp Cell Res. 25(3):585– 621. doi:10.1016/0014­4827(61)90192­6.

Henriksson HB, Svanvik T, Jonsson M, Hagman M, Horn M, Lindahl A, Brisby H. 2009. Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model. Spine. 34(2):141–148. doi:10.1097/BRS.0b013e31818f8c20.

Herberts CA, Kwa MS, Hermsen HP. 2011. Risk factors in the development of stem cell therapy. J Transl Med. 9. doi:10.1186/1479­5876­9­29. Hingert D, Nawilaijaroen P, Aldridge J, Baranto A, Brisby H. 2020. Investigation of the Effect of Secreted Factors from Mesenchymal Stem Cells on Disc Cells from Degenerated Discs. Cells Tissues Organs. 208(1­2):76–88. doi:10.1159/000506350.

Holm S, Maroudas A, Urban JP, Selstam G, Nachemson A. 1981. Nutrition of the intervertebral disc: Solute transport and metabolism. Connect Tissue Res. 8(2):101–119. doi:10.3109/03008208109152130.

Hou T, Xu J, Wu X, Xie Z, Luo F, Zhang Z, Zeng L. 2009. Umbilical cord Wharton’s Jelly: a new potential cell source of mesenchymal stromal cells for bone tissue engineering. Tissue Eng. Part A. 15(9):2325–2334. doi:10.1089/ten.tea.2008.0402.

Hunter CJ, Matyas JR, Duncan NA. 2003. The notochordal cell in the nucleus pulposus: A review in the context of tissue engineering. doi:10.1089/107632703768247368.

Husky MM, Ferdous Farin F, Compagnone P, Fermanian C, Kovess­Masfety V. 2018. Chronic back pain and its association with quality of life in a large French population survey. Health Qual Life Outcomes 16(1):195. doi:10.1186/s12955­018­1018­4.

In ’t Anker PS, Scherjon SA, Kleijburg­van der Keur C, Noort WA, Claas FH, Willemze R, Fibbe WE, Kanhai HH. 2003. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation [1]. Blood. 102(4):1548–1549. doi:10.1182/blood­ 2003­04­1291.

Jezierska­Wozniak K, Barczewska M, Habich A, Wojtacha P, Badowska W, Maksymowicz W, Wojtkiewicz J. 2017. The feasibility of the CD271+ and CD271– mesenchymal stromal cell enrichment toward nucleus pulposus­like cells. Folia Histochem Cytobiol. 55(3):114–123. doi:10.5603/FHC.a2017.0013.

Kagiwada H, Yashiki T, Ohshima A, Tadokoro M, Nagaya N, Ohgushi H. 2008. Human mesenchymal stem cells as a stable source of VEGF­producing cells. J Tissue Eng Regener Med. 2(4):184–189. doi:10.1002/term.79.

Katz JN. 2006. Lumbar disc disorders and lowback pain: Socioeconomic factors and consequences. J Bone Joint Surg. 88(SUPPL. 2):21–24. doi:10.2106/JBJS.E.01273.

Kauppila LI. 2009. Atherosclerosis and Disc Degeneration/Low­Back Pain ­ A Systematic Review. Eur J Vasc Endovasc Surg. 37(6):661–670. doi:10.1016/j.ejvs.2009.02.006.

Keating A. 2012. Mesenchymal stromal cells: New directions. Cell Stem Cell. 10(6):709–716. doi:10.1016/j.stem.2012.05.015.

Kepler CK, Ponnappan RK, Tannoury CA, Risbud MV, Anderson DG. 2013. The molecular basis of intervertebral disc degeneration. Spine J. 13(3):318–330. doi:10.1016/j.spinee.2012.12.003.

Kim YS, Ahn Y, Kwon JS, Cho YK, Jeong MH, Cho JG, Park JC, Kang JC. 2012. Priming of mesenchymal stem cells with oxytocin enhances the cardiac repair in ischemia/reperfusion injury. Cells Tissues Organs. 195(5):428–442. doi:10.1159/000329234.

Kim YS, Hong SW, Choi JP, Shin TS, Moon HG, Choi EJ, Jeon SG, Oh SY, Gho YS, Zhu Z, Kim YK. 2009. Vascular Endothelial Growth Factor Is a Key Mediator in the Development of T Cell Priming and Its Polarization to Type 1 and Type 17 T Helper Cells in the Airways. J Immunol. 183(8):5113–5120. doi:10.4049/jimmunol.0901566.

Kyurkchiev D. 2014. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells. 6(5):552. doi:10.4252/wjsc.v6.i5.552.

Lamichhane TN, Sokic S, Schardt JS, Raiker RS, Lin JW, Jay SM. 2015. Emerging roles for extracellular vesicles in tissue engineering and regenerative medicine. Tissue Eng. ­ Part B: Reviews 21(1):45– 54. doi:10.1089/ten.teb.2014.0300.

Le Maitre CL, Freemont AJ, Hoyland JA. 2007. Accelerated cellular senescence in degenerate intervertebral discs: A possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Res Ther. 9(3):1– 12. doi:10.1186/ar2198.

Li B, Zhang H, Zeng M, He W, Li M, Huang X, Deng DY, Wu J. 2015a. Bone marrow mesenchymal stem cells protect alveolar macrophages from lipopolysaccharide­induced apoptosis partially by inhibiting the Wnt/β­catenin pathway. Cell Biol Int. 39(2):192–200. doi:10.1002/cbin.10359.

Li N, Yang YJ, Qian HY, Li Q, Zhang Q, Li XD, Dong QT, Xu H, Song L, Zhang H. 2015b. Intravenous administration of atorvastatin­pretreated mesenchymal stem cells improves cardiac performance after acute myocardial infarction: Role of CXCR4. Am J Transl Res. 7(6):1058–1070.

Liu J, Zhu P, Song P, Xiong W, Chen H, Peng W, Wang S, Li S, Fu Z, Wang Y, Wang H. 2015. Pretreatment of Adipose Derived Stem Cells with Curcumin Facilitates Myocardial Recovery via Antiapoptosis and Angiogenesis. Stem Cells International 2015. doi:10.1155/2015/638153.

Loibl M, WuertzKozak K, Vadala G, Lang S, Fairbank J, Urban JP. 2019. Controversies in regenerative medicine: Should intervertebral disc degeneration be treated with mesenchymal stem cells? Jor Spine 2(1):e1043. doi:10.1002/jsp2.1043.

Lu Z, Wang G, Dunstan CR, Chen Y, Yenn­Ru Lu W, Davies B, Zreiqat H. 2013. Activation and promotion of adipose stem cells by tumour necrosis factor­alpha preconditioning for bone regeneration. J Cell Physiol. 228(8):1737–1744. doi:10.1002/jcp.24330.

Lv F, Sun Y, Zhou LX, Lu MM, Chan D, Zheng Z, Cheung KMC, Leung VYL. 2014. The Potential of Umbilical Cord Derived Mesenchymal Stem Cells in Intervertebral Disc Repair. Global Spine J. 4(1_suppl). doi:10.1055/s­0034­1376649.

Maacha S, Sidahmed H, Jacob S, Gentilcore G, Calzone R, Grivel JC, Cugno C. 2020. Paracrine Mechanisms of Mesenchymal Stromal Cells in Angiogenesis. Stem Cells Int. 2020. doi:10.1155/2020/4356359.

Madrigal M, Rao KS, Riordan NH. 2014. A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. J Transl Med. 12(1). doi:10.1186/s12967­014­0260­8.

Maguire G. 2013. Stem cell therapy without the cells. Commun Integr Biol. 6(6). doi:10.4161/cib.26631.

Marti LC, Pavon L, Severino P, Sibov T, Guilhen D, Moreira­Filho CA. 2014. Vascular endothelial growth factor­A enhances indoleamine 2,3­dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation. Mem Inst Oswaldo Cruz. 109(1):70–79. doi:10.1590/0074­0276130252.

Matta A, Karim MZ, Isenman DE, Erwin WM. 2017. Molecular Therapy for Degenerative Disc Disease: Clues from Secretome Analysis of the Notochordal Cell­Rich Nucleus Pulposus. Sci Rep. 7. doi:10.1038/srep45623.

McCorry MC, Puetzer JL, Bonassar LJ. 2016. Characterization of mesenchymal stem cells and fibrochondrocytes in three­dimensional co­culture: Analysis of cell shape, matrix production, and mechanical performance. Stem Cell Res Ther. 7(1). doi:10.1186/s13287­016­0301­8.

Mokhbi Soukane D, Shirazi­Adl A, Urban JP. 2007. Computation of coupled diffusion of oxygen, glucose and lactic acid in an intervertebral disc. J Biomech. 40(12):2645–2654. doi:10.1016/j.jbiomech.2007.01.003.

Morito T, Muneta T, Hara K, Ju YJ, Mochizuki T, Makino H, Umezawa A, Sekiya I. 2008. Synovial fluid­derived mesenchymal stem cells increase after intra­articular ligament injury in humans. Rheumatology 47(8):1137–1143. doi:10.1093/rheumatology/ken114.

Moya A, Larochette N, Paquet J, Deschepper M, Bensidhoum M, Izzo V, Kroemer G, Petite H, Logeart­Avramoglou D. 2017. Quiescence Preconditioned Human Multipotent Stromal Cells Adopt a Metabolic Profile Favorable for Enhanced Survival under Ischemia. Stem Cells. 35(1):181–196. doi:10.1002/stem.2493.

Mwale F, Roughley P, Antoniou J, Alini M, Hollander A, Kirsch T, Stokes I. 2004. Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: A requisite for tissue engineering of intervertebral disc. EurCells Mater. 8:58–64. doi:10.22203/eCM.v008a06.

Nakamura Y, Miyaki S, Ishitobi H, Matsuyama S, Nakasa T, Kamei N, Akimoto T, Higashi Y, Ochi M. 2015. Mesenchymal­stem­cellderived exosomes accelerate skeletal muscle regeneration. FEBS Lett. 589(11):1257–1265. doi:10.1016/j.febslet.2015.03.031.

Németh K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, Hu X, Jelinek I, Star RA, Mezey É. 2009. Bone marrow stromal cells attenuate sepsis via prostaglandin E 2­dependent reprogramming of host macrophages to increase their interleukin­10 production. Nat Med. 15(1):42–49. doi:10.1038/nm.1905.

Osugi M, Katagiri W, Yoshimi R, Inukai T, Hibi H, Ueda M. 2012. Conditioned media from mesenchymal stem cells enhanced bone regeneration in rat calvarial bone defects. Tissue Eng.­ Part A 18(13­14):1479–1489. doi:10.1089/ten.tea.2011.0325.

Pérez­Silos V, Camacho­Morales A, Fuentes­Mera L. 2016. Mesenchymal Stem Cells Subpopulations: Application for Orthopedic Regenerative Medicine. Stem Cells Int. 2016. doi:10.1155/2016/3187491.

Pittenger MF, Discher DE, Péault BM, Phinney DG, Hare JM, Caplan AI. 2019. Mesenchymal stem cell perspective: cell biology to clinical progress. npj Regener Med. 4(1). doi:10.1038/s41536­019­0083­6.

Rader DJ, Parmacek MS. 2012. Secreted miRNAs suppress atherogenesis. Nat Cell Biol. 14(3):233–235. doi:10.1038/ncb2452.

Rafei M, Campeau PM, Aguilar­Mahecha A, Buchanan M, Williams P, Birman E, Yuan S, Young YK, Boivin MN, Forner K, Basik M, Galipeau J. 2009. Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Inhibiting CD4 Th17 T Cells in a CC Chemokine Ligand 2­ Dependent Manner. J Immunol. 182(10):5994–6002. doi:10.4049/jimmunol.0803962.

Raynaud CM, Maleki M, Lis R, Ahmed B, Al­Azwani­I, Malek J, Safadi FF, Rafii A. 2012. Comprehensive characterization of mesenchymal stem cells from human placenta and fetal membrane and their response to osteoactivin stimulation. Stem Cells Int. doi:10.1155/2012/658356.

Razaq S, Wilkins RJ, Urban JP. 2003. The effect of extracellular pH on matrix turnover by cells of the bovine nucleus pulposus. Eur Spine J. 12(4):341–349. doi:10.1007/s00586­003­0582­3.

Richardson SM, Hoyland JA, Mobasheri R, Csaki C, Shakibaei M, Mobasheri A. 2010. Mesenchymal stem cells in regenerative medicine: Opportunities and challenges for articular cartilage and intervertebral disc tissue engineering. J Cell Physiol. 222(1):23–32. doi:10.1002/jcp.21915.

Riekstina U, Muceniece R, Cakstina I, Muiznieks I, Ancans J. 2008. Characterization of human skin­derived mesenchymal stem cell proliferation rate in different growth conditions. Cytotechnology. 58(3):153–162. doi:10.1007/s10616­009­9183­2.

Roberts S, Evans H, Trivedi J, Menage J. 2006. Histology and pathology of the human intervertebral disc. J Bone Joint Surg. 88(SUPPL. 2):10–14. doi:10.2106/00004623­200604002­00003.

Roberts S, Urban JP, Evans H, Eisenstein SM. 1996. Transport properties of the human cartilage endplate in relation to its composition and calcification. Spine. 21(4):415–420. doi:10.1097/00007632­199602150­ 00003.

Rodriguez AG, Slichter CK, Acosta FL, RodriguezSoto AE, Burghardt AJ, Majumdar S, Lotz JC. 2011. Human disc nucleus properties and vertebral endplate permeability. Spine. 36(7):512–520. doi:10.1097/BRS.0b013e3181f72b94.

Roorda BD, ter Elst A, Kamps WA, de Bont ES. 2009. Bone marrow­derived cells and tumor growth: Contribution of bone marrow­derived cells to tumor micro­environments with special focus on mesenchymal stem cells. Crit Rev Oncol Hematol. 69(3):187– 198. doi:10.1016/j.critrevonc.2008.06.004.

Ryan JM, Barry FP, Murphy JM, Mahon BP. 2005. Mesenchymal stem cells avoid allogeneic rejection. J Inflammation. 2. doi:10.1186/1476­9255­2­8.

Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K, Hotta T. 2005. Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: Potential and limitations for stem cell therapy in disc regeneration. Spine. 30(21):2379– 2387. doi:10.1097/01.brs.0000184365.28481.e3.

Salgado AJ, Fraga JS, Mesquita AR, Neves NM, Reis RL, Sousa N. 2010. Role of human umbilical cord mesenchymal progenitors conditioned media in neuronal/glial cell densities, viability, and proliferation. Stem Cells Dev. 19(7):1067–1074. doi:10.1089/scd.2009.0279.

Santangelo L, Giurato G, Cicchini C, Montaldo C, Mancone C, Tarallo R, Battistelli C, Alonzi T, Weisz A, Tripodi M. 2016. The RNA­Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA Sorting. Cell Rep. 17(3):799–808. doi:10.1016/j.celrep.2016.09.031.

Schüring AN, Schulte N, Kelsch R, Röpke A, Kiesel L, Götte M. 2011. Characterization of endometrial mesenchymal stem­like cells obtained by endometrial biopsy during routine diagnostics. Fertil Steril. 95(1):423–426. doi:10.1016/j.fertnstert.2010.08.035.

Siemionow K, An H, Masuda K, Andersson G, CsSzabo G. 2011. The Effects of Age, Gender, Ethnicity, and Spinal Level on the Rate of Intervertebral Disc Degeneration. A review of 1712 Intervertebral Discs. Spine (Phila Pa 1976) 36(17):1333– 1339. doi:10.1097/BRS.0b013e3181f2a177.The. URL https://www.ncbi.nlm.nih.gov/pmc/articles/PM C3624763/pdf/nihms412728.pdf.

Smith LJ, Nerurkar NL, Choi KS, Harfe BD, Elliott DM. 2011. Degeneration and regeneration of the intervertebral disc: Lessons from development. Dis Models Mech. 4(1):31–41. doi:10.1242/dmm.006403.

Soliman H, Mediavilla­Varela M, Antonia S. 2010. Indoleamine 2,3­dioxygenase is it an immune suppressor? doi:10.1097/PPO.0b013e3181eb3343.

Strassburg S, Hodson NW, Hill PI, Richardson SM, Hoyland JA. 2012. Bi­directional exchange of membrane components occurs during co­culture of mesenchymal stem cells and nucleus pulposus cells. PLoS ONE. 7(3). doi:10.1371/journal.pone.0033739.

Takahashi H, Suguro T, Okazima Y, Motegi M, Okada Y, Kakiuchi T. 1996. Inflammatory cytokines in the herniated disc of the lumbar spine. Spine. 21(2):218–224. doi:10.1097/00007632­199601150­00011.

Takahashi K, Yamanaka S. 2006. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell. 126(4):663– 676. doi:10.1016/j.cell.2006.07.024.

Tatsumi K, Ohashi K, Matsubara Y, Kohori A, Ohno T, Kakidachi H, Horii A, Kanegae K, Utoh R, Iwata T, Okano T. 2013. Tissue factor triggers procoagulation in transplanted mesenchymal stem cells leading to thromboembolism. Biochem Biophys Res Commun. 431(2):203–209. doi:10.1016/j.bbrc.2012.12.134.

Teixeira GQ, Pereira CL, Ferreira JR, Maia AF, GomezLazaro M, Barbosa MA, Neidlinger­Wilke C, Goncalves RM. 2018. Immunomodulation of Human Mesenchymal Stem/Stromal Cells in Intervertebral Disc Degeneration. Spine. 43(12):E673–E682. doi:10.1097/BRS.0000000000002494.

Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin­Smith GK, Ayre DC, et al. 2018. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 7(1). doi:10.1080/20013078.2018.1535750.

Toussaint O, Medrano EE, Von Zglinicki T. 2000. Cellular and molecular mechanisms of stress­induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes. Exp Gerontol. 35(8):927–945. doi:10.1016/S0531­5565(00)00180­7.

Ullah I, Subbarao RB, Rho GJ. 2015. Human mesenchymal stem cells ­ Current trends and future prospective. Biosci Rep. 35. doi:10.1042/BSR20150025.

Urban JP, Holm S, Maroudas A. 1978. Diffusion of small solutes into the intervertebral disc: An in vivo study. Biorheology. 15(3­4):203–223. doi:10.3233/BIR­ 1978­153­409.

Urban JP, Roberts S. 2003. Degeneration of the intervertebral disc. Arthritis Research and Therapy 5(3):120– 130. doi:10.1186/ar629.

Vadalà G, Russo F, Musumeci M, Valentini A, Bernardini M, Denaro L, D’Avella D, Giordano R, Denaro V. 2016. Disc Regeneration Using MSC Transplanted via the Endplate Route. Global Spine J. 6(1_suppl):s– 0036–1582614–s–0036–1582614. doi:10.1055/s­ 0036­1582614.

Vadalà G, Sowa G, Hubert M, Gilbertson LG, Denaro V, Kang JD. 2012. Mesenchymal stem cells injection in degenerated intervertebral disc: Cell leakage may induce osteophyte formation. J Tissue Eng Regener Med. 6(5):348–355. doi:10.1002/term.433.

Vadalà G, Studer RK, Sowa G, Spiezia F, Iucu C, Denaro V, Gilbertson LG, Kang JD. 2008. Coculture of bone marrow mesenchymal stem cells and nucleus pulposus cells modulate gene expression profile without cell fusion. . 33(8):870–876. doi:10.1097/BRS.0b013e31816b4619.

Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. 2007. Exosome­mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 9(6):654–659. doi:10.1038/ncb1596.

Van Den Eerenbeemt KD, Ostelo RW, Van Royen BJ, Peul WC, Van Tulder MW. 2010. Total disc replacement surgery for symptomatic degenerative lumbar disc disease: A systematic review of the literature. doi:10.1007/s00586­010­1445­3.

Van Elssen CH, Vanderlocht J, Oth T, Senden­Gijsbers BL, Germeraad WT, Bos GM. 2011. Inflammation restraining effects of prostaglandin E2 on natural killer­dendritic cell (NK­DC) interaction are imprinted during DC maturation. Blood. 118(9):2473– 2482. doi:10.1182/blood­2010­09­307835.

Victorelli S, Passos JF. 2017. Telomeres and Cell Senescence ­ Size Matters Not. EBioMedicine. 21:14–20. doi:10.1016/j.ebiom.2017.03.027.

Vizoso FJ, Eiro N, Cid S, Schneider J, Perez­Fernandez R. 2017. Mesenchymal stem cell secretome: Toward cell­free therapeutic strategies in regenerative medicine. Int J Mol Sci. 18(9). doi:10.3390/ijms18091852.

Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, Krause U, Blake J, Schwager C, Eckstein V, Ansorge W, Ho AD. 2005. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol. 33(11):1402–1416. doi:10.1016/j.exphem.2005.07.003.

Walker MH, Anderson DG. 2004. Molecular basis of intervertebral disc degeneration. Spine J. 4(6 SUPPL.):S158–S166. doi:10.1016/j.spinee.2004.07.010.

Wangler S, Kamali A, Wapp C, Wuertz­Kozak K, Häckel S, Fortes C, Benneker LM, Haglund L, Richards RG, Alini M, Peroglio M, Grad S. 2021. Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis. Stem Cell Res Ther. 12(1). doi:10.1186/s13287­020­02062­2.

Wei A, Shen B, Williams L, Diwan A. 2014. Mesenchymal stem cells: potential application in intervertebral disc regeneration. Transl Pediatr. 3(2):71–90. doi:10.3978/j.issn.2224­4336.2014.03.05.

Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF. 2013. Mesenchymal stem cells: A new trend for cell therapy. Acta Pharmacol Sin 34(6):747–754. doi:10.1038/aps.2013.50.

Wilder DG, Pope MH. 1996. Epidemiological and aetiological aspects of low back pain in vibration environments ­ An update. Clin Biomech. 11(2):61–73. doi:10.1016/0268­0033(95)00039­9.

Wu A, March L, Zheng X, Huang J, Wang X, Zhao J, Blyth FM, Smith E, Buchbinder R, Hoy D. 2020. Global low back pain prevalence and years lived with disability from 1990 to 2017: estimates from the Global Burden of Disease Study 2017. Ann Transl Med. 8(6):299– 299. doi:10.21037/atm.2020.02.175.

Wuertz K, Godburn K, Iatridis JC. 2009. MSC response to pH levels found in degenerating intervertebral discs. Biochem Biophys Res. Commun. 379(4):824–829. doi:10.1016/j.bbrc.2008.12.145.

Yamamoto Y, Mochida J, Sakai D, Nakai T, Nishimura K, Kawada H, Hotta T. 2004. Upregulation of the viability of nucleus pulposus cells by bone marrow­derived stromal cells: Significance of direct cell­to­cell contact in coculture system. Spine. 29(14):1508–1514. doi:10.1097/01.BRS.0000131416.90906.20.

Yao LT, Zhao Q, Qin X, Shen L, Cheng L, Ge J, Phillips MI. 2005. Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. Ann Thorac Surg. 80(1):229–237. doi:10.1016/j.athoracsur.2005.02.072.

Yoshimura A, Muto G. 2011. TGF­β function in immune suppression. Curr Top Microbiol Immunol. 350:127– 47. doi:10.1007/82.

Zanotti L, Angioni R, Calì B, Soldani C, Ploia C, Moalli F, Gargesha M, D’Amico G, Elliman S, Tedeschi G, Maffioli E, Negri A, Zacchigna S, Sarukhan A, Stein JV, Viola A. 2016. Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP­1. Leukemia. 30(5):1143–1154. doi:10.1038/leu.2016.33.

Zhang Y, Chopp M, Meng Y, Katakowski M, Xin H, Mahmood A, Xiong Y. 2015. Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. J Neurosurg. 122(4):856–867. doi:10.3171/2014.11.JNS14770.

Zhu W, Huang L, Li Y, Zhang X, Gu J, Yan Y, Xu X, Wang M, Qian H, Xu W. 2012. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 315(1):28–37. doi:10.1016/j.canlet.2011.10.002.



DOI: https://doi.org/10.22146/ijbiotech.63318

Article Metrics

Abstract views : 6907 | views : 4592

Refbacks

  • There are currently no refbacks.


Copyright (c) 2021 The Author(s)

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.