Skip to main content

Current Situation of Regenerative Medicine

  • Chapter
Regenerative Medicine in Otolaryngology

Abstract

Regenerative medicine has made remarkable progress. This has been supported by the development of tissue engineering, which was a combination of medicine and engineering. Tissue engineering applies the principles and methods of engineering, material science, and cell and molecular biology toward the development of viable substitutes that restore, maintain, or improve the function of human tissues.

According to the theories of tissue engineering, tissues and organs can be regenerated by manipulating three elements: cells, scaffolds, and regulation factors. In this field, cells mean stem cells that possess both capabilities of self-renewal and differentiation into various tissue-specific cells. Stem cells are divided into three groups: embryonic stem cells (ES cells), somatic stem cells, and induced pluripotent stem (iPS) cells. Although ES cells are the best cell-source having the omnipotency to generate all tissues, ethical problems and rejections by the immune system remain to be resolved. On the other hand, somatic stem cells are promising cell-sources because they are free of the above problems. Actually, almost all clinical applications of regenerative medicine have been performed using somatic stem cells or progenitor cells.

Mesenchymal stem cells (MSCs) belonging to somatic stem cells are defined as pluripotent progenitor cells with the ability to generate bone, cartilage, muscle, tendon, ligament, and fat. Moreover, in some kind of conditions, MSCs can be differentiated into another lineage: nerve, epithelium, and so on. These properties have generated great interest in the potential use of MSCs to replace damaged tissues. Mesenchymal stem cells could be cultured to expand their numbers or after or seeded in/on shaped biomimetic scaffold to generate appropriate tissue constructs, then transplanted to the injured site.

The iPS cells have been considered to be comparable to ES cells and are promising cell-sources as substitutes for ES cells. Generation of iPS cells has dramatically changed the landscape of stem cell research and its future clinical application. Especially, it is possible that novel drug discovery using iPS cell-based disease models/toxicity screening can be useful in filling the gap between animal models and clinical trials.

A scaffold that sustains cells is necessary to regenerate injured tissues and organs. Owing to the development of biotechnology and polymer chemistry, we can create more desirable biomaterial scaffolds with appropriate mechanical properties that can be modified to incorporate biological activity, such as growth factors and structural adhesive proteins. It is no exaggeration to say that successful regeneration of tissues and organs depends on how to establish an appropriate scaffold in the injured site.

Regulation factors also play an important role in tissue regeneration. They can induce angiogenesis, which promotes a sufficient supply of oxygen and nutrients to effectively maintain the biological functions of cells transplanted for organ substitution. Therefore, if we do not understand and manipulate the complex relationships among cells, scaffolds, and regulation factors, we cannot repair and/or regenerate tissues and organs.

This chapter discusses the basic principles of tissue engineering and introduces current situations of regenerative medicines.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Langer R, Vacanti JP. Tissue engineering. Science. 1993;260:920–6.

    Article  CAS  PubMed  Google Scholar 

  2. Vacanti JP, Morse MA, Saltzman WM, Domb AJ, Perez-Atayde A, Langer R. Selective cell transplantation using bioabsorbable artificial polymers as matrices. J Pediatr Surg. 1988;23:3–9.

    Article  CAS  PubMed  Google Scholar 

  3. Vacanti CA, Kim W, Upton J, Vacanti MP, Mooney D, Schloo B, Vacanti JP. Tissue-engineered growth of bone and cartilage. Transplant Proc. 1993;25:1019–21.

    CAS  PubMed  Google Scholar 

  4. Suzuki S, Kawai K, Ashoori F, Morimoto N, Nishimura Y, Ikada Y. Long-term follow-up study of artificial dermis composed of outer silicone layer and inner collagen sponge. Br J Plast Surg. 2000;53:659–66.

    Article  CAS  PubMed  Google Scholar 

  5. Tsai RJ, Li LM, Chen JK. Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells. N Engl J Med. 2000;343:86–93.

    Article  CAS  PubMed  Google Scholar 

  6. Owaki T, Shimizu T, Yamato M, Okano T. Cell sheet engineering for regenerative medicine: current challenges and strategies. Biotechnol J. 2014;9:904–14.

    Google Scholar 

  7. Elloumi-Hannachi I, Yamato M, Okano T. Cell sheet engineering: a unique nanotechnology for scaffold-free tissue reconstruction with clinical applications in regenerative medicine. J Intern Med. 2010;267:54–70.

    Article  CAS  PubMed  Google Scholar 

  8. Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998;91:756–63.

    CAS  PubMed  Google Scholar 

  9. Lindvall O, Rehncrona S, Brundin P, Gustavii B, Astedt B, Widner H, Lindholm T, Bjorklund A, Leenders KL, Rothwell JC, et al. Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson’s disease. A detailed account of methodology and a 6-month follow-up. Arch Neurol. 1989;46:615–31.

    Article  CAS  PubMed  Google Scholar 

  10. Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med. 2001;344:710–9.

    Article  CAS  PubMed  Google Scholar 

  11. Leor J, Patterson M, Quinones MJ, Kedes LH, Kloner RA. Transplantation of fetal myocardial tissue into the infarcted myocardium of rat. A potential method for repair of infarcted myocardium? Circulation. 1996;94(9 Suppl):II332–6.

    CAS  PubMed  Google Scholar 

  12. Nakamura T, Teramachi M, Sekine T, Kawanami R, Fukuda S, Yoshitani M, Toba T, Ueda H, Hori Y, Inoue M, Shigeno K, Taka TN, Liu Y, Tamura N, Shimizu Y. Artificial trachea and long term follow-up in carinal reconstruction in dogs. Int J Artif Organs. 2000;23:718–24.

    CAS  PubMed  Google Scholar 

  13. Kanemaru S, Nakamura T, Omori K, Kojima H, Magrufov A, Hiratsuka Y, Ito J, Shimizu Y. Recurrent laryngeal nerve regeneration by tissue engineering. Ann Otol Rhinol Laryngol. 2003;112:492–8.

    Article  PubMed  Google Scholar 

  14. Omori K, Nakamura T, Kanemaru S, Kojima H, Magrufov A, Hiratsuka Y, Shimizu Y. Cricoid regeneration using in situ tissue engineering in canine larynx for the treatment of subglottic stenosis. Ann Otol Rhinol Laryngol. 2004;113:623–7.

    Article  PubMed  Google Scholar 

  15. Nakahara T, Nakamura T, Kobayashi E, Kuremoto K, Matsuno T, Tabata Y, Eto K, Shimizu Y. In situ tissue engineering of periodontal tissues by seeding with periodontal ligament-derived cells. Tissue Eng. 2004;10:537–44.

    Article  CAS  PubMed  Google Scholar 

  16. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–7.

    Article  CAS  PubMed  Google Scholar 

  17. Xu C, Inokuma MS, Denham J, Golds K, Kundu P, Gold JD, Carpenter MK. Feeder-free growth of undifferentiated human embryonic stem cells. Nat Biotechnol. 2001;19:971–4.

    Article  CAS  PubMed  Google Scholar 

  18. Wiles MV. Embryonic stem cell differentiation in vitro. Methods Enzymol. 1993;225:900–18.

    Article  CAS  PubMed  Google Scholar 

  19. Guan K, Chang H, Rolletschek A, Wobus AM. Embryonic stem cell-derived neurogenesis. Retinoic acid induction and lineage selection of neuronal cells. Cell Tissue Res. 2001;305:171–6.

    Article  CAS  PubMed  Google Scholar 

  20. Wichterle H, Lieberam I, Porter JA, Jessell TM. Directed differentiation of embryonic stem cells into motor neurons. Cell. 2002;110:385–97.

    Article  CAS  PubMed  Google Scholar 

  21. Reubinoff BE, Itsykson P, Turetsky T, Pera MF, Reinhartz E, Itzik A, Ben-Hur T. Neural progenitors from human embryonic stem cells. Nat Biotechnol. 2001;19:1134–40.

    Article  CAS  PubMed  Google Scholar 

  22. Nakano T, Kodama H, Honjo T. Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science. 1994;265:1098–101.

    Article  CAS  PubMed  Google Scholar 

  23. Kehat I, Kenyagin-Karsenti D, Snir M, Segev H, Amit M, Gepstein A, Livne E, Binah O, Itskovitz-Eldor J, Gepstein L. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest. 2001;108:407–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Levenberg S, Golub JS, Amit M, Itskovitz-Eldor J, Langer R. Endothelial cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A. 2002;99:4391–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.

    Article  CAS  PubMed  Google Scholar 

  26. Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell. 2001;105:369–77.

    Article  CAS  PubMed  Google Scholar 

  27. Zhao LR, Duan WM, Reyes M, Keene CD, Verfaillie CM, Low WC. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol. 2002;174:11–20.

    Article  PubMed  Google Scholar 

  28. Rodeheffer MS, Birsoy JM. Friedman identification of white adipocyte progenitor cells in vivo. Cell. 2008;135:240–9.

    Article  CAS  PubMed  Google Scholar 

  29. Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011;9:11–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7:211–28.

    Article  CAS  PubMed  Google Scholar 

  31. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418:41–9.

    Article  CAS  PubMed  Google Scholar 

  32. Kanemaru S, Nakamura T, Omori K, Kojima H, Magrufov A, Hiratsuka Y, Hirano S, Ito J, Shimizu Y. Regeneration of the vocal fold using autologous mesenchymal stem cells. Ann Otol Rhinol Laryngol. 2003;112:915–20.

    Article  PubMed  Google Scholar 

  33. Takahashi K, Ymanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

    Article  CAS  PubMed  Google Scholar 

  34. Takahashi K, Ymanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.

    Article  CAS  PubMed  Google Scholar 

  35. Maekawa M, Yamaguchi K, Nakamura T, Shibukawa R, Kodanaka I, Ichisaka T, Kawamura Y, Mochizuki H, Goshima N, Yamanaka S. Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1. Nature. 2011;474:225–9.

    Article  CAS  PubMed  Google Scholar 

  36. Maeda T, Lee MJ, Palczewska G, Marsili S, Tesar PJ, Palczewski K, Takahashi M, Maeda A. Retinal pigmented epithelial cells obtained from human induced pluripotent stem cells possess functional visual cycle enzymes in vitro and in vivo. J Biol Chem. 2013;288:34484–93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Yahata N, Asai M, Kitaoka S, Takahashi K, Asaka I, Hioki H, Kaneko T, Maruyama K, Saido TC, Nakahata T, Asada T, Yamanaka S, Iwata N, Inoue H. Anti-Aβ drug screening platform using human iPS cell-derived neurons for the treatment of Alzheimer’s disease. PLoS One. 2011;6:e25788. doi:10.1371/journal.pone.0025788.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Nagata N, Yamanaka S. Perspectives for induced pluripotent stem cell technology: new insights into human physiology involved in somatic mosaicism. Circ Res. 2014;114:505–10.

    Article  CAS  PubMed  Google Scholar 

  39. Amit M, Carpenter MK, Inokuma MS, Chiu CP, Harris CP, Waknitz MA, Itskovitz-Eldor J, Thomson JA. Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture. Dev Biol. 2000;227:271–8.

    Article  CAS  PubMed  Google Scholar 

  40. Maniatopoulos C, Sodek J, Melcher AH. Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats. Cell Tissue Res. 1988;254:317–30.

    Article  CAS  PubMed  Google Scholar 

  41. Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, Sano M, Takahashi T, Hori S, Abe H, Hata J, Umezawa A, Ogawa S. Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest. 1999;103:697–705.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Kohyama J, Abe H, Shimazaki T, Koizumi A, Nakashima K, Gojo S, Taga T, Okano H, Hata J, Umezawa A. Brain from bone: efficient “meta-differentiation” of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent. Differentiation. 2001;68:235–44.

    Article  CAS  PubMed  Google Scholar 

  43. Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie CM. Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood. 2001;98:2615–25.

    Article  CAS  PubMed  Google Scholar 

  44. Colter DC, Sekiya I, Prockop DJ. Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proc Natl Acad Sci U S A. 2001;98:7841–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Young HE, Steele TA, Bray RA, Hudson J, Floyd JA, Hawkins K, Thomas K, Austin T, Edwards C, Cuzzourt J, Duenzl M, Lucas PA, Black Jr AC. Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec. 2001;264:51–62.

    Article  CAS  PubMed  Google Scholar 

  46. Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585–621.

    Article  CAS  PubMed  Google Scholar 

  47. Kiyono T, Foster SA, Koop JI, McDougall JK, Galloway DA, Klingelhutz AJ. Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature. 1998;396:84–8.

    Article  CAS  PubMed  Google Scholar 

  48. Okamoto T, Aoyama T, Nakayama T, Nakamata T, Hosaka T, Nishijo K, Nakamura T, Kiyono T, Toguchida J. Clonal heterogeneity in differentiation potential of immortalized human mesenchymal stem cells. Biochem Biophys Res Commun. 2002;295:354–61.

    Article  CAS  PubMed  Google Scholar 

  49. Rubio D, Garcia-Castro J, Martin MC, de la Fuente R, Cigudosa JC, Lloyd AC, Bernad A. Spontaneous human adult stem cell transformation. Cancer Res. 2005;65:3035–9.

    CAS  PubMed  Google Scholar 

  50. Nakamura T, Inada Y, Fukuda S, Yoshitani M, Nakada A, Itoi S, Kanemaru S, Endo K, Shimizu Y. Experimental study on the regeneration of peripheral nerve gaps through a polyglycolic acid-collagen (PGA-collagen) tube. Brain Res. 2004;1027:18–29.

    Article  CAS  PubMed  Google Scholar 

  51. Hutmacher D, Hurzeler MB, Schliephake H. A review of material properties of biodegradable and bioresorbable polymers and devices for GTR and GBR applications. Int J Oral Maxillofac Implants. 1996;11:667–78.

    CAS  PubMed  Google Scholar 

  52. Pollok JM, Lorenzen M, Kolln PA, Torok E, Kaufmann PM, Kluth D, Bohuslavizki KH, Gundlach M, Rogiers X. In vitro function of islets of Langerhans encapsulated with a membrane of porcine chondrocytes for immunoisolation. Dig Surg. 2001;18:204–10.

    Article  CAS  PubMed  Google Scholar 

  53. Oie Y, Hayashi R, Takagi R, Yamato M, Takayanagi H, Tano Y, Nishida K. A novel method of culturing human oral mucosal epithelial cell sheet using post-mitotic human dermal fibroblast feeder cells and modified keratinocyte culture medium for ocular surface reconstruction. Br J Ophthalmol. 2010;94:1244–50.

    Article  PubMed  Google Scholar 

  54. Sawa Y, Miyagawa S. Present and future perspectives on cell sheet-based myocardial regeneration therapy. Biomed Res Int. 2013;2013:583912. doi:10.1155/2013/583912.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Takagi R, Yamato M, Kanai N, Murakami D, Kondo M, Ishii T, Ohki T, Namiki H, Yamamoto M, Okano T. Cell sheet technology for regeneration of esophageal mucosa. World J Gastroenterol. 2012;18:5145–50.

    PubMed Central  PubMed  Google Scholar 

  56. Iwata T, Yamato M, Tsuchioka H, Takagi R, Mukobata S, Washio K, Okano T, Ishikawa I. Periodontal regeneration with multi-layered periodontal ligament-derived cell sheets in a canine model. Biomaterials. 2009;30:2716–23.

    Article  CAS  PubMed  Google Scholar 

  57. Metsger DS, Driskell TD, Paulsrud JR. Tricalcium phosphate ceramic – a resorbable bone implant: review and current status. J Am Dent Assoc. 1982;105:1035–8.

    Article  CAS  PubMed  Google Scholar 

  58. Szpalski M, Gunzburg R. Applications of calcium phosphate-based cancellous bone void fillers in trauma surgery. Orthopedics. 2002;25(5 Suppl):s601–9.

    PubMed  Google Scholar 

  59. Magrufov A, Kanemaru S, Nakamura T, Omori K, Yamashita M, Shimizu Y, Ito J. Tissue engineering for the regeneration of the mastoid air cells: a preliminary in vitro study. Acta Otolaryngol Suppl. 2004;551:75–9.

    Article  PubMed  Google Scholar 

  60. Kanemaru S, Nakamura T, Omori K, Magrufov A, Yamashita M, Ito J. Regeneration of mastoid air cells in clinical applications by in situ tissue engineering. Laryngoscope. 2005;115:253–8.

    Article  CAS  PubMed  Google Scholar 

  61. Kanemaru S, Umeda H, Kitani Y, Nakamura T, Hirano S, Ito J. Regenerative treatment for tympanic membrane perforation. Otol Neurotol. 2011;32:1218–23.

    Article  PubMed  Google Scholar 

  62. Kanemaru S, Umeda H, Kanai R, Tsuji T, Kuboshima F, Yamamoto M, Hirano S, Nakamura T. Regenerative treatment for soft tissue defects of the external auditory meatus. Otol Neurotol. 2014;35:442–8.

    Article  PubMed  Google Scholar 

  63. Kishimoto Y, Hirano S, Kitani Y, Suehiro A, Umeda H, Tateya I, Kanemaru S, Tabata Y, Ito J. Chronic vocal fold scar restoration with hepatocyte growth factor hydrogel. Laryngoscope. 2010;120:108–13.

    Article  PubMed  Google Scholar 

  64. Kretzschmar M, Doody J, Timokhina I, Massague J. A mechanism of repression of TGFbeta/Smad signaling by oncogenic Ras. Genes Dev. 1999;13:804–16.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Nusse R, Varmus HE. Wnt genes. Cell. 1992;69:1073–87.

    Article  CAS  PubMed  Google Scholar 

  66. Cadigan KM, Nusse R. Wnt signaling: a common theme in animal development. Genes Dev. 1997;11:3286–305.

    Article  CAS  PubMed  Google Scholar 

  67. Schuldiner M, Yanuka O, Itskovitz-Eldor J, Melton DA, Benvenisty N. Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A. 2000;97:11307–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Tabata Y. Recent progress in tissue engineering. Drug Discov Today. 2001;6:483–7.

    Article  CAS  PubMed  Google Scholar 

  69. Yamamoto M, Ikada Y, Tabata Y. Controlled release of growth factors based on biodegradation of gelatin hydrogel. J Biomater Sci Polym Ed. 2001;12:77–88.

    Article  CAS  PubMed  Google Scholar 

  70. Aoyama T, Hosseinkhani H, Yamamoto S, Ogawa O, Tabata Y. Enhanced expression of plasmid DNA-cationized gelatin complex by ultrasound in murine muscle. J Control Release. 2002;80:345–56.

    Article  CAS  PubMed  Google Scholar 

  71. Baumgartner I, Pieczek A, Manor O, Blair R, Kearney M, Walsh K, Isner JM. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation. 1998;97:1114–23.

    Article  CAS  PubMed  Google Scholar 

  72. Losordo DW, Vale PR, Symes JF, Dunnington CH, Esakof DD, Maysky M, Ashare AB, Lathi K, Isner JM. Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation. 1998;98:2800–4.

    Article  CAS  PubMed  Google Scholar 

  73. Hedman M, Yla-Herttuala S. Gene therapy for the treatment of peripheral vascular disease and coronary artery disease. Drugs Today (Barc). 2000;36:609–17.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shin-ichi Kanemaru MD, PhD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Japan

About this chapter

Cite this chapter

Kanemaru, Si. (2015). Current Situation of Regenerative Medicine. In: Ito, J. (eds) Regenerative Medicine in Otolaryngology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54856-0_1

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-54856-0_1

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-54855-3

  • Online ISBN: 978-4-431-54856-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics