Skip to main content
SpringerLink
Log in

Regenerative Medicine: Advances from Developmental to Degenerative Diseases

  • Chapter
  • First Online:
Book cover Personalised Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1007))

Abstract

Chronic tissue and organ failure caused by an injury, disease, ageing or congenital defects represents some of the most complex therapeutic challenges and poses a significant financial healthcare burden. Regenerative medicine strategies aim to fulfil the unmet clinical need by restoring the normal tissue function either through stimulating the endogenous tissue repair or by using transplantation strategies to replace the missing or defective cells. Stem cells represent an essential pillar of regenerative medicine efforts as they provide a source of progenitors or differentiated cells for use in cell replacement therapies. Whilst significant leaps have been made in controlling the stem cell fates and differentiating them to cell types of interest, transitioning bespoke cellular products from an academic environment to off-the-shelf clinical treatments brings about a whole new set of challenges which encompass manufacturing, regulatory and funding issues. Notwithstanding the need to resolve such issues before cell replacement therapies can benefit global healthcare, mounting progress in the field has highlighted regenerative medicine as a realistic prospect for treating some of the previously incurable conditions.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
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. Mason C, Dunnill P (2008) A brief definition of regenerative medicine. Regen Med 3:1–5. doi:10.2217/17460751.3.1.1

    Article  PubMed  Google Scholar 

  2. Nikolich-Zugich J et al (2016) Preparing for an aging world: engaging biogerontologists, geriatricians, and the society. J Gerontol A Biol Sci Med Sci 71:435–444. doi:10.1093/gerona/glv164

    Article  PubMed  Google Scholar 

  3. Burt RK et al (2008) Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. JAMA 299:925–936. doi:10.1001/jama.299.8.925

    Article  CAS  PubMed  Google Scholar 

  4. Moore KA, Lemischka IR (2006) Stem cells and their niches. Science 311:1880–1885. doi:10.1126/science.1110542

    Article  CAS  PubMed  Google Scholar 

  5. Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    Article  CAS  PubMed  Google Scholar 

  6. Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78:7634–7638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Thomson JA et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  CAS  PubMed  Google Scholar 

  8. Till JE, Mc CE (1961) A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 14:213–222

    Article  CAS  PubMed  Google Scholar 

  9. Becker AJ, Mc CE, Till JE (1963) Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:452–454

    Article  CAS  PubMed  Google Scholar 

  10. Thomas ED (1999) A history of haemopoietic cell transplantation. Br J Haematol 105:330–339

    Article  CAS  PubMed  Google Scholar 

  11. Osawa M, Hanada K, Hamada H, Nakauchi H (1996) Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 273:242–245

    Article  CAS  PubMed  Google Scholar 

  12. Majeti R, Park CY, Weissman IL (2007) Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood. Cell Stem Cell 1:635–645. doi:10.1016/j.stem.2007.10.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Barker N, van de Wetering M, Clevers H (2008) The intestinal stem cell. Genes Dev 22:1856–1864. doi:10.1101/gad.1674008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Potten CS, Kovacs L, Hamilton E (1974) Continuous labelling studies on mouse skin and intestine. Cell Tissue Kinet 7:271–283

    CAS  PubMed  Google Scholar 

  15. Barker N, Clevers H (2007) Tracking down the stem cells of the intestine: strategies to identify adult stem cells. Gastroenterology 133:1755–1760. doi:10.1053/j.gastro.2007.10.029

    Article  CAS  PubMed  Google Scholar 

  16. Sato T et al (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459:262–265. doi:10.1038/nature07935

    Article  CAS  PubMed  Google Scholar 

  17. Eriksson PS et al (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317. doi:10.1038/3305

    Article  CAS  PubMed  Google Scholar 

  18. Lois C, Alvarez-Buylla A (1993) Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci U S A 90:2074–2077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Casarosa S, Bozzi Y, Conti L (2014) Neural stem cells: ready for therapeutic applications? Mol Cell Ther 2:31. doi:10.1186/2052-8426-2-31

    Article  PubMed  PubMed Central  Google Scholar 

  20. Tabar V, Studer L (2014) Pluripotent stem cells in regenerative medicine: challenges and recent progress. Nat Rev Genet 15:82–92. doi:10.1038/nrg3563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Takahashi K et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872. doi:10.1016/j.cell.2007.11.019

    Article  CAS  PubMed  Google Scholar 

  22. International Stem Cell, I et al (2007) Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat Biotechnol 25:803–816. doi:10.1038/nbt1318

    Article  Google Scholar 

  23. Hentze H et al (2009) Teratoma formation by human embryonic stem cells: evaluation of essential parameters for future safety studies. Stem Cell Res 2:198–210. doi:10.1016/j.scr.2009.02.002

    Article  PubMed  Google Scholar 

  24. Damjanov I, Andrews PW (2016) Teratomas produced from human pluripotent stem cells xenografted into immunodeficient mice – a histopathology atlas. Int J Dev Biol 60:337–419. doi:10.1387/ijdb.160274id

    Article  PubMed  PubMed Central  Google Scholar 

  25. Murry CE, Keller G (2008) Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell 132:661–680. doi:10.1016/j.cell.2008.02.008

    Article  CAS  PubMed  Google Scholar 

  26. Osafune K et al (2008) Marked differences in differentiation propensity among human embryonic stem cell lines. Nat Biotechnol 26:313–315. doi:10.1038/nbt1383

    Article  CAS  PubMed  Google Scholar 

  27. Wichterle H, Lieberam I, Porter JA, Jessell TM (2002) Directed differentiation of embryonic stem cells into motor neurons. Cell 110:385–397

    Article  CAS  PubMed  Google Scholar 

  28. Williams LA, Davis-Dusenbery BN, Eggan KC (2012) SnapShot: directed differentiation of pluripotent stem cells. Cell 149:1174–1174 e1171. doi:10.1016/j.cell.2012.05.015

    Article  CAS  PubMed  Google Scholar 

  29. Trounson A, DeWitt ND (2016) Pluripotent stem cells progressing to the clinic. Nat Rev Mol Cell Biol 17:194–200. doi:10.1038/nrm.2016.10

    Article  CAS  PubMed  Google Scholar 

  30. Varma AK et al (2013) Spinal cord injury: a review of current therapy, future treatments, and basic science frontiers. Neurochem Res 38:895–905. doi:10.1007/s11064-013-0991-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Irvine KA, Blakemore WF (2008) Remyelination protects axons from demyelination-associated axon degeneration. Brain 131:1464–1477. doi:10.1093/brain/awn080

    Article  CAS  PubMed  Google Scholar 

  32. Faulkner J, Keirstead HS (2005) Human embryonic stem cell-derived oligodendrocyte progenitors for the treatment of spinal cord injury. Transpl Immunol 15:131–142. doi:10.1016/j.trim.2005.09.007

    Article  CAS  PubMed  Google Scholar 

  33. Nistor GI, Totoiu MO, Haque N, Carpenter MK, Keirstead HS (2005) Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 49:385–396. doi:10.1002/glia.20127

    Article  PubMed  Google Scholar 

  34. Yasuda A et al (2011) Significance of remyelination by neural stem/progenitor cells transplanted into the injured spinal cord. Stem Cells 29:1983–1994. doi:10.1002/stem.767

    Article  PubMed  Google Scholar 

  35. All AH et al (2015) Early intervention for spinal cord injury with human induced pluripotent stem cells oligodendrocyte progenitors. PLoS One 10:e0116933. doi:10.1371/journal.pone.0116933

    Article  PubMed  PubMed Central  Google Scholar 

  36. Lebkowski J (2011) GRNOPC1: the world’s first embryonic stem cell-derived therapy. Interview with Jane Lebkowski. Regen Med 6:11–13. doi:10.2217/rme.11.77

    Article  PubMed  Google Scholar 

  37. Baker M (2011) Stem-cell pioneer bows out. Nature 479:459. doi:10.1038/479459a

    Article  CAS  PubMed  Google Scholar 

  38. de Lau LM, Breteler MM (2006) Epidemiology of Parkinson’s disease. Lancet Neurol 5:525–535. doi:10.1016/S1474-4422(06)70471-9

    Article  PubMed  Google Scholar 

  39. Hely MA et al (1999) The sydney multicentre study of Parkinson’s disease: progression and mortality at 10 years. J Neurol Neurosurg Psychiatry 67:300–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Barker RA, Drouin-Ouellet J, Parmar M (2015) Cell-based therapies for Parkinson disease-past insights and future potential. Nat Rev Neurol 11:492–503. doi:10.1038/nrneurol.2015.123

    Article  CAS  PubMed  Google Scholar 

  41. Kefalopoulou Z et al (2014) Long-term clinical outcome of fetal cell transplantation for Parkinson disease: two case reports. JAMA Neurol 71:83–87. doi:10.1001/jamaneurol.2013.4749

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kriks S et al (2011) Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature 480:547–551. doi:10.1038/nature10648

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Grealish S et al (2014) Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson’s disease. Cell Stem Cell 15:653–665. doi:10.1016/j.stem.2014.09.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Barker RA, Studer L, Cattaneo E, Takahashi J (2015) G-Force PD: a global initiative in coordinating stem cell-based dopamine treatments for Parkinson’s disease. Npj Parkinson’s Disease 1:15017. doi:10.1038/npjparkd.2015.17

    Article  PubMed  PubMed Central  Google Scholar 

  45. Li W et al (2016) Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain. Proc Natl Acad Sci U S A 113:6544–6549. doi:10.1073/pnas.1605245113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Morizane A, Takahashi J (2016) Cell therapy for Parkinson’s disease. Neurol Med Chir (Tokyo) 56:102–109. doi:10.2176/nmc.ra.2015-0303

    Article  Google Scholar 

  47. Scudellari M (2016) How iPS cells changed the world. Nature 534:310–312. doi:10.1038/534310a

    Article  PubMed  Google Scholar 

  48. Barker RA et al (2016) Are stem cell-based therapies for Parkinson’s disease ready for the clinic in 2016? J Parkinsons Dis 6:57–63. doi:10.3233/JPD-160798

    Article  PubMed  PubMed Central  Google Scholar 

  49. McKeown SJ, Stamp L, Hao MM, Young HM (2013) Hirschsprung disease: a developmental disorder of the enteric nervous system. Wiley Interdiscip Rev Dev Biol 2:113–129. doi:10.1002/wdev.57

    Article  CAS  PubMed  Google Scholar 

  50. Sasselli V, Pachnis V, Burns AJ (2012) The enteric nervous system. Dev Biol 366:64–73. doi:10.1016/j.ydbio.2012.01.012

    Article  CAS  PubMed  Google Scholar 

  51. Lake JI, Heuckeroth RO (2013) Enteric nervous system development: migration, differentiation, and disease. Am J Physiol Gastrointest Liver Physiol 305:G1–24. doi:10.1152/ajpgi.00452.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Burns AJ et al (2016) White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies. Dev Biol 417:229–251. doi:10.1016/j.ydbio.2016.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Burns AJ, Thapar N (2014) Neural stem cell therapies for enteric nervous system disorders. Nat Rev Gastroenterol Hepatol 11:317–328. doi:10.1038/nrgastro.2013.226

    Article  PubMed  Google Scholar 

  54. Bondurand N, Natarajan D, Thapar N, Atkins C, Pachnis V (2003) Neuron and glia generating progenitors of the mammalian enteric nervous system isolated from foetal and postnatal gut cultures. Development 130:6387–6400. doi:10.1242/dev.00857

    Article  CAS  PubMed  Google Scholar 

  55. Cooper JE et al (2016) In vivo transplantation of enteric neural crest cells into mouse gut; engraftment, functional integration and long-term safety. PLoS One 11:e0147989. doi:10.1371/journal.pone.0147989

    Article  PubMed  PubMed Central  Google Scholar 

  56. Fattahi F et al (2016) Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease. Nature 531:105–109. doi:10.1038/nature16951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Workman MJ et al (2017) Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat Med 23:49–59. doi:10.1038/nm.4233

    Article  CAS  PubMed  Google Scholar 

  58. Xu B et al (2013) Non-linear elasticity of core/shell spun PGS/PLLA fibres and their effect on cell proliferation. Biomaterials 34:6306–6317. doi:10.1016/j.biomaterials.2013.05.009

    Article  CAS  PubMed  Google Scholar 

  59. Burridge PW et al (2014) Chemically defined generation of human cardiomyocytes. Nat Methods 11:855–860. doi:10.1038/nmeth.2999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lippmann ES, Estevez-Silva MC, Ashton RS (2014) Defined human pluripotent stem cell culture enables highly efficient neuroepithelium derivation without small molecule inhibitors. Stem Cells 32:1032–1042. doi:10.1002/stem.1622

    Article  CAS  PubMed  Google Scholar 

  61. Bao X, Lian X, Palecek SP (2016) Directed endothelial progenitor differentiation from human pluripotent stem cells via Wnt activation under defined conditions. Methods Mol Biol 1481:183–196. doi:10.1007/978-1-4939-6393-5_17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Cheung C, Bernardo AS, Trotter MW, Pedersen RA, Sinha S (2012) Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility. Nat Biotechnol 30:165–173. doi:10.1038/nbt.2107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Jonsson MK et al (2012) Application of human stem cell-derived cardiomyocytes in safety pharmacology requires caution beyond hERG. J Mol Cell Cardiol 52:998–1008. doi:10.1016/j.yjmcc.2012.02.002

    Article  CAS  PubMed  Google Scholar 

  64. van den Berg CW et al (2015) Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent stem cells. Development 142:3231–3238. doi:10.1242/dev.123810

    Article  PubMed  Google Scholar 

  65. Berger DR, Ware BR, Davidson MD, Allsup SR, Khetani SR (2015) Enhancing the functional maturity of induced pluripotent stem cell-derived human hepatocytes by controlled presentation of cell-cell interactions in vitro. Hepatology 61:1370–1381. doi:10.1002/hep.27621

    Article  CAS  PubMed  Google Scholar 

  66. Hrvatin S et al (2014) Differentiated human stem cells resemble fetal, not adult, beta cells. Proc Natl Acad Sci U S A 111:3038–3043. doi:10.1073/pnas.1400709111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Cornacchia D, Studer L (2017) Back and forth in time: directing age in iPSC-derived lineages. Brain Res 1656:14–26. doi:10.1016/j.brainres.2015.11.013

    Article  CAS  PubMed  Google Scholar 

  68. Wu H et al (2007) Integrative genomic and functional analyses reveal neuronal subtype differentiation bias in human embryonic stem cell lines. Proc Natl Acad Sci U S A 104:13821–13826. doi:10.1073/pnas.0706199104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Nishizawa M et al (2016) Epigenetic variation between human induced pluripotent stem cell lines is an indicator of differentiation capacity. Cell Stem Cell 19:341–354. doi:10.1016/j.stem.2016.06.019

    Article  CAS  PubMed  Google Scholar 

  70. Gu E, Chen WY, Gu J, Burridge P, Wu JC (2012) Molecular imaging of stem cells: tracking survival, biodistribution, tumorigenicity, and immunogenicity. Theranostics 2:335–345. doi:10.7150/thno.3666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. van Laake LW, Passier R, Doevendans PA, Mummery CL (2008) Human embryonic stem cell-derived cardiomyocytes and cardiac repair in rodents. Circ Res 102:1008–1010. doi:10.1161/CIRCRESAHA.108.175505

    Article  PubMed  Google Scholar 

  72. Zhang YW, Denham J, Thies RS (2006) Oligodendrocyte progenitor cells derived from human embryonic stem cells express neurotrophic factors. Stem Cells Dev 15:943–952. doi:10.1089/scd.2006.15.943

    Article  CAS  PubMed  Google Scholar 

  73. Lui KO et al (2014) Tolerance induction to human stem cell transplants with extension to their differentiated progeny. Nat Commun 5:5629. doi:10.1038/ncomms6629

    Article  CAS  PubMed  Google Scholar 

  74. Figueiredo C, Blasczyk R (2015) A future with less HLA: potential clinical applications of HLA-universal cells. Tissue Antigens 85:443–449. doi:10.1111/tan.12564

    Article  CAS  PubMed  Google Scholar 

  75. Goldring CE et al (2011) Assessing the safety of stem cell therapeutics. Cell Stem Cell 8:618–628. doi:10.1016/j.stem.2011.05.012

    Article  CAS  PubMed  Google Scholar 

  76. Draper JS et al (2004) Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat Biotechnol 22:53–54. doi:10.1038/nbt922

    Article  CAS  PubMed  Google Scholar 

  77. Baker D et al (2016) Detecting genetic mosaicism in cultures of human pluripotent stem cells. Stem Cell Rep 7:998–1012. doi:10.1016/j.stemcr.2016.10.003

    Article  CAS  Google Scholar 

  78. Garber K (2015) RIKEN suspends first clinical trial involving induced pluripotent stem cells. Nat Biotechnol 33:890–891. doi:10.1038/nbt0915-890

    Article  CAS  PubMed  Google Scholar 

  79. Chakradhar S (2016) An eye to the future: researchers debate best path for stem cell-derived therapies. Nat Med 22:116–119. doi:10.1038/nm0216-116

    Article  CAS  PubMed  Google Scholar 

  80. Cyranoski D (2014) Japanese woman is first recipient of next-generation stem cells. Nature. doi:10.1038/nature.2014.15915

Download references

Acknowledgements

We would like to thank Dr Paul J. Gokhale for critical reading of the manuscript. NFB and IB are supported by the UK Regenerative Medicine Platform (grant number MR/L012537/1). IB is also funded by the Medical Research Council (grant number MR/N009371/1) and the European Union’s Horizon 2020 research and innovation programme under grant agreement No 668724.

Author information

Author notes

  1. Nicholas F. Blair and Thomas J.R. Frith contributed equally to this work.

Authors and Affiliations

  1. Wellcome Trust – MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK

    Nicholas F. Blair

  2. Centre for Stem Cell Biology, Department of Biomedical Science, The University of Sheffield, Sheffield, UK

    Thomas J. R. Frith & Ivana Barbaric

Authors
  1. Nicholas F. Blair
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas J. R. Frith
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ivana Barbaric
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ivana Barbaric .

Editor information

Editors and Affiliations

  1. Krebs Institute and Sheffield Institute for Nucleic Acids, Department of Molecular Biology and Biotechnology, Firth Court, University of Sheffield, Sheffield, United Kingdom

    Sherif El-Khamisy

Rights and permissions

Reprints and permissions

Copyright information

© 2017 American Association of Pharmaceutical Scientists

About this chapter

Cite this chapter

Blair, N.F., Frith, T.J.R., Barbaric, I. (2017). Regenerative Medicine: Advances from Developmental to Degenerative Diseases. In: El-Khamisy, S. (eds) Personalised Medicine. Advances in Experimental Medicine and Biology, vol 1007. Springer, Cham. https://doi.org/10.1007/978-3-319-60733-7_12

Download citation

Publish with us

Policies and ethics

Search

Navigation