Molecular Mechanism of Autonomy and Self-Organization: An Emerging Concept for the Future of Biomedical Sciences

  • Tara Karimi


The whole human body can be considered as a precisely programmed system. The entire physiological functions of the human body is regulated through a hierarchical (multilayer) molecular coding system. Disorder in any part of this coding system causes misfunction in the physiological functions in the human body which also can be defined as diseases. Deep understanding of the regulatory mechanisms behind the physiological functions at different layers of these molecular coding systems can open new avenues toward the treatment of diseases with no current cure. Here, we attempt to classify different diseases based on the etiology of diseases at the molecular coding level. We provide examples of diseases with no current effective cure applying conventional therapeutic approaches.


Protein misfolding diseases Cancer Aging Stem cell-based regenerative medicine Tissue engineering Organoid technology 


  1. 1.
    Adler R, Canto-Soler MV (2007) Molecular mechanism of optic vesicle development: complexities, ambiguities, and controversies. Dev Biol 305:1–13CrossRefGoogle Scholar
  2. 2.
    Agathocleous M, Harris WA (2009) From progenitors to differentiated cells in the vertebrate retina. Annu Rev Cell Dev Biol 25:45–69CrossRefGoogle Scholar
  3. 3.
    Barker N et al (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–1007CrossRefGoogle Scholar
  4. 4.
    Brabletz T (2012) EMT and MET in Metastasis: Where Are the Cancer Stem Cells?. Cancer Cell 22 (6):699–701CrossRefGoogle Scholar
  5. 5.
    Bressan RB et al (2017) Efficient CRISPR/Cas9-assisted gene targeting enables rapid and precise genetic manipulation of mammalian neural stem cells. Development, 144(4), 635–648.CrossRefGoogle Scholar
  6. 6.
    Dean DM, Napolitano AP, Youssef J, Morgan JR (2007) Rods, tori, and honeycombs: the directed self-assembly of microtissues with prescribed microscale geometries. FASEB J 21(14):4005–4012CrossRefGoogle Scholar
  7. 7.
    Detrick RJ et al (1990) The effects of N-cadherin misexpression on morphogenesis in Xenopus embryos. Neuron 4:493–506CrossRefGoogle Scholar
  8. 8.
    Eiraku M et al (2011) Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472:51–56CrossRefGoogle Scholar
  9. 9.
    Eiraku M et al (2012) Relaxation- expansion model for self-driver retinal morphogenesis: a hypothesis from the perspective of biosystems dynamics at the multi-cellular level. BioEssays 34:17–25CrossRefGoogle Scholar
  10. 10.
    Esteve P, Bovolenta P (2006) Secreted inducers in vertebrate eye development: more functions for old morphogens. Curr Opin Neurobiol 16:13–19CrossRefGoogle Scholar
  11. 11.
    Foty RA et al (1996) Surface tensions of embryonic tissues predict their mutual envelopment behavior. Development 122:1611–1620PubMedGoogle Scholar
  12. 12.
    Fuhrmann S (2006) Wnt signaling in eye organogenesis. Organogenesis 4:60–67CrossRefGoogle Scholar
  13. 13.
    Fujimori T et al (1990) Ectopic expression of N-cadherin perturbs histogenesis in Xenopus embryos. Development 110:97–104PubMedPubMedCentralGoogle Scholar
  14. 14.
    Gauvin R, Ahsan T, Larouche D, Levesque P, Dube J, Auger FA, Nerem RM, Germain L (2010) A novel single-step self-assembly approach for the fabrication of tissue-engineered vascular constructs. Tissue Eng Part A 16(5):1737–1747CrossRefGoogle Scholar
  15. 15.
    Gilbert S (2000) Developmental biology, 6th edn. Sinauer Associates, Sunderland, MAGoogle Scholar
  16. 16.
    Gjorevski N et al (2014) Bioengineering approaches to guide stem cell-based organogenesis, the company of biologists. Development 141:1794–1804CrossRefGoogle Scholar
  17. 17.
    Grayson WL, Martens TP, Eng GM, Radisic M, Vunjak-Novakovic G (2009) Biomimetic approach to tissue engineering. Semin Cell Dev Biol 20(6):665–673CrossRefGoogle Scholar
  18. 18.
    Hadjimichael C (2015) Common Stemness regulators of embryonic and cancer stem cells. World J Stem Cells 7(9):1150–1189PubMedPubMedCentralGoogle Scholar
  19. 19.
    Hindley C et al (2016) Organoids from adult liver and pancreas: stem cell biology and biomedical utility. Dev Biol 420:251–261CrossRefGoogle Scholar
  20. 20.
    Humphreys BD (2014) Kidney structures differentiated from stem cells. Nat Cell Biol 16:19–21CrossRefGoogle Scholar
  21. 21.
     Ishiwata T (2016) Cancer stem cells and epithelial-mesenchymal transition: Novel therapeutic targets for cancer. Pathology International 66 (11):601–608CrossRefGoogle Scholar
  22. 22.
    Jabbari E (2011) Bioconjugation of hydrogels for tissue engineering. Curr Opin Biotechnol 22(5):655–660CrossRefGoogle Scholar
  23. 23.
    Jakab K, Norotte C, Marga F, Murphy K, Vunjak-Novakovic G, Forgacs G (2010) Tissue engineering by self-assembly and bio-printing of living cells. Biofabrication 2(2):022001CrossRefGoogle Scholar
  24. 24.
    Kachouie NN, Du Y, Bae H, Khabiry M, Ahari AF, Zamanian B, Fukuda J, Khademhosseini A (2010) Directed assembly of cell-laden hydrogels for engineering functional tissues. Organogenesis 6(4):234–244CrossRefGoogle Scholar
  25. 25.
    Kobel S, Lutolf MP (2011) Biomaterials meet microfluidics: building the next generation of artificial niches. Curr Opin Biotechnol 22(5):690–697CrossRefGoogle Scholar
  26. 26.
    Kretzschmar K, Clever H (2016) Organoids: modeling development and the stem cell niche in a dish. Dev Cell 38:590–600CrossRefGoogle Scholar
  27. 27.
    Lancaster M, Knoblich JA (2014) Organogenesis in a dish: modeling development and disease using organoid technology. Science 345(6194):1–9CrossRefGoogle Scholar
  28. 28.
    Little MH, McMahon MP (2012) Mammalian kidney development: principles, progress, and projections. Cold Spring Harb Perspect Biol 4:a008300. pmid: 22550230CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Livoti CM, Morgan JR (2010) Self-assembly and tissue fusion of toroid-shaped minimal building units. Tissue Eng Part A 16(6):2051–2061CrossRefGoogle Scholar
  30. 30.
    Lund AW (2009) The natural and engineered 3D microenvironment as a regulatory cue during stem cell fate determination. Tissue Eng Part B 15(3):371–380CrossRefGoogle Scholar
  31. 31.
    Lutolf M, Blau H (2009) Artificial stem cell niches. Adv Mater 21:3255–3268CrossRefGoogle Scholar
  32. 32.
    Mironov V, Visconti RP, Kasyanov V, Forgacs G, Drake CJ, Markwald RR (2009) Organ printing: tissue spheroids as building blocks. Biomaterials 30(12):2164–2174CrossRefGoogle Scholar
  33. 33.
    Miranov V, Kasyanov V, Markward RR (2011) Organ printing: from bioprinter to organ biofabrication line. Curr Opin Biotechnol 22:667–673CrossRefGoogle Scholar
  34. 34.
    Miyajiamn A et al (2014) Stem/progenitor cells in liver development, homeostasis, regeneration and reprogramming. Cell Stem Cell 14(5):561–574CrossRefGoogle Scholar
  35. 35.
    Moscona A (1961) Rotation-mediated histogenetic aggregation of dissociated cells. A quantifiable approach to cell interactions in vitro. Exp Cell Res 22:455–475CrossRefGoogle Scholar
  36. 36.
    Oh J et al (2014) Stem cell aging; mechanisms, regulators and therapeutic opportunities. Nat Med 20(8):870–880CrossRefGoogle Scholar
  37. 37.
    Park D et al (2015) Stem cell microenvironment on a chip, current technologies for tissue engineering and stem cell biology. Stem Cell Transl Med 4:1352–1368CrossRefGoogle Scholar
  38. 38.
    Rodriguez- Seguel E et al (2013) Mutually exclusive signaling signatures define the hepatic and pancreatic progenitor cell lineage divergence. Genes Dev 27(17):1932–1946CrossRefGoogle Scholar
  39. 39.
    Rossi JM et al (2001) Distinct mesodermal signals, including BMPs form the septum transversum mesenchyme are required in combination for hepatogenesis from the endoderm. Genes Dev 15(15):1998–2009CrossRefGoogle Scholar
  40. 40.
    Rothermel A et al (1997) Pigmented epithelium induces complete retinal reconstitution from dispersed embryonic chick retinae in reaggregation culture. Proc Biol Sci 264:1293–1302CrossRefGoogle Scholar
  41. 41.
    Sato T, Clevers H (2013) Growing self-organizing mini-gut from a single intestinal stem cell: mechanism and applications. Science 340:1190–1194CrossRefGoogle Scholar
  42. 42.
    Sato T et al (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchyma niche. Nature 459:262–265CrossRefGoogle Scholar
  43. 43.
    Schultz MB, Sinclair DA (2016) When stem cells grow old: phenotypes and mechanisms of stem cell aging. Development 143:3–14CrossRefGoogle Scholar
  44. 44.
    Steinberg MS (1964) In: Locke M (ed) Cellular membranes in development. Academic Press, New York, pp 321–366CrossRefGoogle Scholar
  45. 45.
    Sweeney P et al (2017) Protein misfolding in neurodegenerative diseases: implications and strategies. Transl Neurodegeneration 6:1–13CrossRefGoogle Scholar
  46. 46.
    Takebe T et al (2013) Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499:481–484CrossRefGoogle Scholar
  47. 47.
    Taguchi A et al (2014) Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells. Cell Stem Cell 14:53–67CrossRefGoogle Scholar
  48. 48.
    Takasato M, Little M (2016) A strategy for generating kidney organoids; recapitulating the development of human pluripotent stem cells. Dev Biol 420:210–220CrossRefGoogle Scholar
  49. 49.
    Takasato M et al (2014) Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. Nat. Cell Biol. 16:118–126Google Scholar
  50. 50.
    Valastyan J, Lindquist S (2014) Mechanisms of protein folding diseases at a glance. Dis Model Mech 7(1):9–14CrossRefGoogle Scholar
  51. 51.
    Weiss P, Taylor AC (1960) Reconstitution of complete organs from single-cell suspensions of chick embryos in advanced stages of differentiation. Proc Natl Acad Sci U S A 46:1177–1185CrossRefGoogle Scholar
  52. 52.
    Wolpert L (2007) Principles of development, 3rd edn. Oxford University Press, OxfordGoogle Scholar
  53. 53.
    Xia Y et al (2013) Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. Nat. Cell Biol 15:1507–1515Google Scholar
  54. 54.
    Yabut O, Bernstein H (2011) The promise of human embryonic stem cells in aging-associated diseases. Aging 3(5):494–508CrossRefGoogle Scholar
  55. 55.
    Yin X et al (2016) Engineering stem cell organoids. Cell Stem Cell 18:25–37CrossRefGoogle Scholar
  56. 56.
    Žigman M et al (2005) Mammalian inscuteable regulates spindle orientation and cell fate in the developing retina. Neuron 48:539–545CrossRefGoogle Scholar
  57. 57.
    Zhang Z et al (2017) CRISPR/Cas9 Genome-Editing System in Human Stem Cells: Current Status and Future Prospects. Mol Ther Nucleic Acids, 9, 230–241.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Tara Karimi
    • 1
  1. 1.Tulane Medical CenterTulane UniversityNew OrleansUSA

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