Abstract
Regenerative medicine is an emerging interdisciplinary field which involves the regeneration of the damaged or diseased cells, tissues or organs in order to restore the normal biological function. There has been significant improvements in the development of cell based therapies; however, current treatment strategies still suffer from some problems: the need for long in vitro culture conditions, inefficient delivery of cells by scaffolds and low incorporation and grafting efficiencies. Therefore, in vivo reprogramming has emerged as a novel treatment technology. In the process of in vivo reprogramming, cells switch to another cell type within the living organism. There are successful studies which make use of this technology and hence offer therapeutic options for various organs or tissues.
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References
Chen L, Tredget EE, Liu C, Wu Y. Analysis of allogenicity of mesenchymal stem cells in engraftment and wound healing in mice. PLoS One. 2009;4(9):e7119. doi:10.1371/journal.pone.0007119.
Mallick KK, Cox SC. Biomaterial scaffolds for tissue engineering. Front Biosci (Elite Ed). 2013;5:341–60. doi:10.2741/e620.
Ilic D, Polak JM. Stem cells in regenerative medicine: introduction. Br Med Bull. 2011;98:117–26. doi:10.1093/bmb/ldr012.
Alvarez CV, Garcia-Lavandeira M, Garcia-Rendueles ME, Diaz-Rodriguez E, Garcia-Rendueles AR, Perez-Romero S, Vila TV, Rodrigues JS, Lear PV, Bravo SB. Defining stem cell types: understanding the therapeutic potential of ESCs, ASCs, and iPS cells. J Mol Endocrinol. 2012;49(2):R89–R111. doi:10.1530/JME-12-0072.
Xue L, Xu YB, Xie JL, Tang JM, Shu B, Chen L, Qi SH, Liu XS. Effects of human bone marrow mesenchymal stem cells on burn injury healing in a mouse model. Int J Clin Exp Pathol. 2013;6(7):1327–36.
Gurdon JB. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol. 1962;10(4):622–40.
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.
Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA. In vivo reprogramming of adult pancreatic exocrine cells to [bgr]-cells. Nature. 2008;455(7213):627–32.
Inagawa K, Miyamoto K, Yamakawa H, Muraoka N, Sadahiro T, Umei T, Wada R, Katsumata Y, Kaneda R, Nakade K, Kurihara C, Obata Y, Miyake K, Fukuda K, Ieda M. Induction of cardiomyocyte-like cells in infarct hearts by gene transfer of Gata4, Mef2c, and Tbx5. Circ Res. 2012;111(9):1147–56. doi:10.1161/CIRCRESAHA.112.271148.
Qian L, Huang Y, Spencer CI, Foley A, Vedantham V, Liu L, Conway SJ, Fu J-d, Srivastava D. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature. 2012;485(7400):593–8. doi:10.1038/nature11044. http://www.nature.com/nature/journal/v485/n7400/abs/nature11044.html#supplementary-information
Song K, Nam Y-J, Luo X, Qi X, Tan W, Huang GN, Acharya A, Smith CL, Tallquist MD, Neilson EG, Hill JA, Bassel-Duby R, Olson EN. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature. 2012;485(7400):599–604. doi:10.1038/nature11139. http://www.nature.com/nature/journal/v485/n7400/abs/nature11139.html#supplementary-information
Jayawardena TM, Egemnazarov B, Finch EA, Zhang L, Alan Payne J, Pandya K, Zhang Z, Rosenberg P, Mirotsou M, Dzau VJ. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res. 2012;110(11):1465–73. doi:10.1161/CIRCRESAHA.112.269035.
Ruff CA, Wilcox JT, Fehlings MG. Cell-based transplantation strategies to promote plasticity following spinal cord injury. Exp Neurol. 2012;235(1):78–90. doi:10.1016/j.expneurol.2011.02.010.
Tetzlaff W, Okon EB, Karimi-Abdolrezaee S, Hill CE, Sparling JS, Plemel JR, Plunet WT, Tsai EC, Baptiste D, Smithson LJ, Kawaja MD, Fehlings MG, Kwon BK. A systematic review of cellular transplantation therapies for spinal cord injury. J Neurotrauma. 2010;28(8):1611–82. doi:10.1089/neu.2009.1177.
Su Z, Niu W, Liu M-L, Zou Y, Zhang C-L. In vivo conversion of astrocytes to neurons in the injured adult spinal cord. Nat Commun. 2014;5:3338. doi:10.1038/ncomms4338. http://dharmasastra.live.cf.private.springer.com/articles/ncomms4338#supplementary-information
Wang L-L, Su Z, Tai W, Zou Y, Xu X-M, Zhang C-L. The p53 pathway controls SOX2-mediated reprogramming in the adult mouse spinal cord. Cell Rep. 2016;17(3):891–903. doi:10.1016/j.celrep.2016.09.038.
Gao X, Wang X, Xiong W, Chen J. In vivo reprogramming reactive glia into iPSCs to produce new neurons in the cortex following traumatic brain injury. Sci Rep. 2016;6:22490. doi:10.1038/srep22490. http://dharmasastra.live.cf.private.springer.com/articles/srep22490#supplementary-information
Cox CS, Hetz RA, Liao GP, Aertker BM, Ewing-Cobbs L, Juranek J, Savitz SI, Jackson ML, Romanowska-Pawliczek AM, Triolo F, Dash PK, Pedroza C, Lee DA, Worth L, Aisiku IP, Choi HA, Holcomb JB, Kitagawa RS. Treatment of severe adult traumatic brain injury using bone marrow mononuclear cells. Stem Cells. 2017;35(4):1065–79. doi:10.1002/stem.2538.
Harting MT, Baumgartner JE, Worth LL, Ewing-Cobbs L, Gee AP, Day M-C, Cox CS. Cell therapies for traumatic brain injury. Neurosurg Focus. 2008;24(0):E18. doi:10.3171/FOC/2008/24/3-4/E17.
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.
Heinrich C, Bergami M, Gascón S, Lepier A, Viganò F, Dimou L, Sutor B, Berninger B, Götz M. Sox2 mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex. Stem Cell Rep. 2014;3(6):1000–14. doi:10.1016/j.stemcr.2014.10.007.
Kim JB, Lee H, Araúzo-Bravo MJ, Hwang K, Nam D, Park MR, Zaehres H, Park KI, Lee S-J. Oct4-induced oligodendrocyte progenitor cells enhance functional recovery in spinal cord injury model. EMBO J. 2015;34(23):2971–83. doi:10.15252/embj.201592652.
Niu W, Zang T, Smith Derek K, Vue Tou Y, Zou Y, Bachoo R, Johnson Jane E, Zhang C-L. SOX2 reprograms resident astrocytes into neural progenitors in the adult brain. Stem Cell Rep. 2015;4(5):780–94. doi:10.1016/j.stemcr.2015.03.006.
Niu W, Zang T, Zou Y, Fang S, Smith DK, Bachoo R, Zhang C-L. In vivo reprogramming of astrocytes to neuroblasts in the adult brain. Nat Cell Biol. 2013;15(10):1164–75. doi:10.1038/ncb2843.
Grande A, Sumiyoshi K, López-Juárez A, Howard J, Sakthivel B, Aronow B, Campbell K, Nakafuku M. Environmental impact on direct neuronal reprogramming in vivo in the adult brain. Nat Commun. 2013;4:2373. doi:10.1038/ncomms3373. http://dharmasastra.live.cf.private.springer.com/articles/ncomms3373#supplementary-information
Torper O, Pfisterer U, Wolf DA, Pereira M, Lau S, Jakobsson J, Björklund A, Grealish S, Parmar M. Generation of induced neurons via direct conversion in vivo. Proc Natl Acad Sci. 2013;110(17):7038–43. doi:10.1073/pnas.1303829110.
Wolters RJ, Braspenning JCC, Wensing M. Impact of primary care on hospital admission rates for diabetes patients: a systematic review. Diabetes Res Clin Pract. 2017;129:182–96. doi:10.1016/j.diabres.2017.05.001.
Adeniyi A, Anjana R, Weber M. Global account of barriers and facilitators of physical activity among patients with diabetes mellitus: a narrative review of the literature. Curr Diabetes Rev. 2016;12(4):440–8.
Baeyens L, Lemper M, Leuckx G, De Groef S, Bonfanti P, Stange G, Shemer R, Nord C, Scheel DW, Pan FC, Ahlgren U, Gu G, Stoffers DA, Dor Y, Ferrer J, Gradwohl G, Wright CVE, Van de Casteele M, German MS, Bouwens L, Heimberg H. Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice. Nat Biotechnol. 2014;32(1):76–83. doi:10.1038/nbt.2747. http://www.nature.com/nbt/journal/v32/n1/abs/nbt.2747.html#supplementary-information
Cavelti-Weder C, Li W, Zumsteg A, Stemann-Andersen M, Zhang Y, Yamada T, Wang M, Lu J, Jermendy A, Bee YM, Bonner-Weir S, Weir GC, Zhou Q. Hyperglycaemia attenuates in vivo reprogramming of pancreatic exocrine cells to beta cells in mice. Diabetologia. 2016;59(3):522–32. doi:10.1007/s00125-015-3838-7.
Miyazaki S, Tashiro F, J-i M. Transgenic expression of a single transcription factor Pdx1 induces transdifferentiation of pancreatic acinar cells to endocrine cells in adult mice. PLoS One. 2016;11(8):e0161190. doi:10.1371/journal.pone.0161190.
Banga A, Akinci E, Greder LV, Dutton JR, Slack JMW. In vivo reprogramming of Sox9+ cells in the liver to insulin-secreting ducts. Proc Natl Acad Sci U S A. 2012;109(38):15336–41. doi:10.1073/pnas.1201701109.
Rezvani M, Español-Suñer R, Malato Y, Dumont L, Grimm Andrew A, Kienle E, Bindman Julia G, Wiedtke E, Hsu Bernadette Y, Naqvi Syed J, Schwabe Robert F, Corvera Carlos U, Grimm D, Willenbring H. In vivo hepatic reprogramming of myofibroblasts with AAV vectors as a therapeutic strategy for liver fibrosis. Cell Stem Cell. 2016;18(6):809–16. doi:10.1016/j.stem.2016.05.005.
Song G, Pacher M, Balakrishnan A, Yuan Q, Tsay H-C, Yang D, Reetz J, Brandes S, Dai Z, Pützer Brigitte M, Araúzo-Bravo Marcos J, Steinemann D, Luedde T, Schwabe Robert F, Manns Michael P, Schöler Hans R, Schambach A, Cantz T, Ott M, Sharma Amar D. Direct reprogramming of hepatic myofibroblasts into hepatocytes in vivo attenuates liver fibrosis. Cell Stem Cell. 2016;18(6):797–808. doi:10.1016/j.stem.2016.01.010.
Yilmazer A, de Lázaro I, Bussy C, Kostarelos K. In vivo cell reprogramming towards pluripotency by virus-free overexpression of defined factors. PLoS One. 2013;8(1):e54754. doi:10.1371/journal.pone.0054754.
Yechoor V, Liu V, Espiritu C, Paul A, Oka K, Kojima H, Chan L. Neurogenin3 is sufficient for transdetermination of hepatic progenitor cells into neo-islets in vivo but not transdifferentiation of hepatocytes. Dev Cell. 2009;16(3):358–73. doi:10.1016/j.devcel.2009.01.012.
Jayawardena TM, Finch EA, Zhang L, Zhang H, Hodgkinson CP, Pratt RE, Rosenberg PB, Mirotsou M, Dzau VJ. MicroRNA induced cardiac reprogramming in vivo evidence for mature cardiac myocytes and improved cardiac function. Circ Res. 2015;116(3):418–24. doi:10.1161/CIRCRESAHA.116.304510.
Murry CE, Kay MA, Bartosek T, Hauschka SD, Schwartz SM. Muscle differentiation during repair of myocardial necrosis in rats via gene transfer with MyoD. J Clin Investig. 1996;98(10):2209–17. doi:10.1172/JCI119030.
Hu Y-F, Dawkins JF, Cho HC, Marbán E, Cingolani E. Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block. Sci Transl Med. 2014;6(245):245ra294. doi:10.1126/scitranslmed.3008681.
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Gurcan, C., Taheri, H., Yilmazer, A. (2017). Introduction to In Vivo Cell Reprogramming Technology. In: Yilmazer, A. (eds) In Vivo Reprogramming in Regenerative Medicine. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-65720-2_1
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DOI: https://doi.org/10.1007/978-3-319-65720-2_1
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