Inflammation Research

, Volume 67, Issue 2, pp 111–116 | Cite as

The gestational power of mast cells in the injured tissue

  • Maria-Angeles Aller
  • Natalia Arias
  • Vicente Martínez
  • Patri Vergara
  • Jaime Arias


The inflammatory response expressed after wound healing would be the recapitulation of systemic extra-embryonic functions, which would focus on the interstitium of the injured tissue. In the injured tissue, mast cells, provided for a great functional heterogeneity, could play the leading role in the re-expression of extra-embryonic functions, i.e., coelomic–amniotic and trophoblastic–vitelline. Moreover, mast cells would favor the production of a gastrulation-like process, which in certain tissues and organs would induce the regeneration of the injured tissue. Therefore, the engraftment of mesenchymal stem cells and mast cells, both with an extra-embryonic regenerative phenotype, would achieve a blastema, from the repaired and regenerated injured tissue, rather than by fibrosis, which is commonly made through wound-healing.


Mast cells Mesenchymal stem cells Wound healing Regeneration Embryonic Amnion Yolk sac 


  1. 1.
    Norton R, Kobusingye O. Injuries. N Engl J Med. 2013;368:1723–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Harper D, Young A, McNaught CE. The physiology of wound healing. Surgery (Oxford) 2014;32:445–50.CrossRefGoogle Scholar
  3. 3.
    Portou MJ, Baker D, Abraham D, Tsui J. The innate immune system, toll-like receptors and dermal wound healing: a review. Vascul Pharmacol. 2015;71:31–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Aller MA, Arias JI, Arraez-Aybar LA, Gilsanz C, Arias J. Wound healing reaction: a switch from gestation to senescence. World J Exp Med. 2014;4:16–26.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Childs DR, Murthy AS. Overview of wound healing and management. Surg Clin N Am. 2017;97:189–207.CrossRefPubMedGoogle Scholar
  6. 6.
    Frykberg RG, Banks J. Challenges in the treatment of chronic wounds. Adv Wound Care. 2015;4(9):560–76.CrossRefGoogle Scholar
  7. 7.
    Sorci G, Faivre B. Inflammation and oxidative stress in vertebrate host–parasite systems. Philos Trans R Soc Lond B Biol Sci. 2009;364:71–83.CrossRefPubMedGoogle Scholar
  8. 8.
    Strachan DP. Family size, infection and atopy: the first decade of the “hygiene hypothesis”. Thorax. 2000;55(Suppl 1):S2–10.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Nathan C. Points of control in inflammation. Nature 2002;420:848–52.CrossRefGoogle Scholar
  10. 10.
    Libby P. Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutr Rev. 2007;65(12Pt2):S140–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Okin B, Medzhitov R. Evolution of inflammatory diseases. Curr Biol. 2012;22:R733–40.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kotas ME, Medzhitov R. Homeostasis, inflammation and disease susceptibility. Cell 2015;160:816–27.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Straub RH, Schradin C. Chronic inflammatory systemic diseases. An evolutionary trade-off between acutely beneficial but chronically harmful programs. Evol Med Public Health. 2016;2016:37–51.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Bangi E. Drosophila at the intersection of infection, inflammation and cancer. Front Cell Infect Microbiol. 2013;3:1–6.CrossRefGoogle Scholar
  15. 15.
    Wang L, Kounatidis I, Ligoxygakis P. Drosophila as a model to study the role of blood cells in inflammation, innate immunity and cancer. Front Cell Infect Microbiol. 2014;3:1–17.CrossRefGoogle Scholar
  16. 16.
    Chandramore K, Ghaskadbi S. Evo-devo: hydra raises its Noggin. J Biosci. 2011;36:517–29.CrossRefPubMedGoogle Scholar
  17. 17.
    Campos-Ramos G. Inflammation as an animal development phenomenon. Clin Dev Immunol. 2012;2012:983203.Google Scholar
  18. 18.
    Aller MA, Arias N, Fuentes-Julian S, Blazquez-Martinez A, Argudo S, De Miguel MP, Arias JL, Arias J. Coupling inflammation with evo-devo. Med Hypotheses. 2012;78:721–31.CrossRefPubMedGoogle Scholar
  19. 19.
    Aller MA, Arias JI, Prieto J, Gilsanz C, Arias A, Yang H, Arias J. Surgical inflammatory stress: the embryo takes hold of the reins again. Theor Biol Med Model. 2013;10:6.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Moon TC, Befus AD, Kulka M. Mast cell mediators: their differential release and the secretory pathways involved. Front Immunol. 2014;5:1–18.CrossRefGoogle Scholar
  21. 21.
    Krystel-Whittemore M, Dileepan KN, Wood JG. Mast cell: a multi-functional master cell. Front Immunol. 2016;6:1–12.CrossRefGoogle Scholar
  22. 22.
    Arodz T, Bonchev D, Diegelmann RF. A network approach to wound healing. Adv Wound Care. 2013;2:499–509.CrossRefGoogle Scholar
  23. 23.
    Kalkhof S, Förster Y, Schmidt J, Schulz MC, Baumann S, Weibflog A, Gao W, Hempel U, Eckelt U, Rammelt S, Von Bergen M. Proteomics and metabolomics for in situ monitoring of wound healing. Bio Med Res Int. 2014;2014:1–12.CrossRefGoogle Scholar
  24. 24.
    Takemoto CM, Lee Y-N, Jegga AG, Zablocki D, Brandal S, Shahlaee A, Huang S, Ye Y, Gowrisankar S, Huynh J, McDevitt MA. Mast cell transcriptional networks. Blood Cells Mol Dis. 2008;41:82–90.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Clark RAF. Basics of cutaneous wound repair. J Demartol Surg Oncol. 1993;19:693–706.CrossRefGoogle Scholar
  26. 26.
    Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanism. J Invest Dermatol. 2007;127:514–25.CrossRefPubMedGoogle Scholar
  27. 27.
    Goldberg SR, Diegelmann RF. Wound healing primer. Surg Clin N Am. 2010;90:1133–46.CrossRefPubMedGoogle Scholar
  28. 28.
    Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res. 2012;49:35–43.CrossRefPubMedGoogle Scholar
  29. 29.
    Rose LF, Chan RK. The burn wound microenviroment. Adv Wound Care 2016;5:106–12.CrossRefGoogle Scholar
  30. 30.
    Aller MA, Arias JI, Nava MP, Arias J. Post-traumatic inflammation is a complex response based in the pathological expression of the nervous, immune and endocrine functional systems. Exp Biol Med 2004;229:170–81.CrossRefGoogle Scholar
  31. 31.
    Rohen JW, Lütjen-Drecoll E. Funktionelle embryologie Schattauer GmbH. Stuttgart Germany 2006;1–162.Google Scholar
  32. 32.
    Crivellato E, Ribatti D. The mast cell: an evolutionary perspective. Biol Rev 2010;85:347–60.CrossRefPubMedGoogle Scholar
  33. 33.
    Singh J, Shah R, Singh D. Targeting mast cells: uncovering prolific therapeutic role in myriad diseases. Int Immunopharmacol. 2016;40:362–84.CrossRefPubMedGoogle Scholar
  34. 34.
    Wernersson S, Pejler G. Mast cell secretory granules: armed for battle. Nature Rev Immunol. 2014;14:478–94.CrossRefGoogle Scholar
  35. 35.
    Aller MA, Arias JI, Prieto I, Gilsanz C, Arias JL, Yang H, Arias J. Phases of the acute inflammatory response to the injury. In: Arias J, Aller MA, Arias JI, editors. Surgical inflammation, chap. 4. USA: Bentham Science; 2013. pp. 99–128.CrossRefGoogle Scholar
  36. 36.
    Aller MA, Arias JI, Giner M, Losada M, Cruz A, Alonso-Pozas A, Arias J. Oxygen-related inflammatory wound phenotypes. In: Middleton JE, editors. Wound healing: process, phases and promoting, Chap. 2. Huntington: Nova Sciences; 2011. pp. 1–26.Google Scholar
  37. 37.
    Uberti MG, Pierpont YN, Ko F, Wright TE, Smith CA, Cruse CW, Robson MC, Payne WG. Amnion-derived cellular cytokine solution (ACCS) promotes migration of keratinocytes and fibroblasts. Ann Plast Surg. 2010;64:632–5.PubMedGoogle Scholar
  38. 38.
    Dovaiher J, Succar J, Lancerotto L, Gurish MF, Orgill DP, Hamilton MJ, Krillis SA, Stevens RL. Development of mast cells and importance of their tryphase and chymasa serine proteases in inflammation and wound healing. Adv Immunol. 2014;122:211–52.CrossRefGoogle Scholar
  39. 39.
    Wong VW, Gurtner CG, Longaker MT. Woung healing: a paradigm for regeneration. Mayo Clin Proc. 2013;88:1022–31.CrossRefPubMedGoogle Scholar
  40. 40.
    Aller MA, Blanco-Rivero J, Arias JI, Balfagon G, Arias J. The wound-healing response and upregulated embryonic mechanisms: brothers-in-arms forever. Exper Dermatol. 2012;21:497–503.CrossRefGoogle Scholar
  41. 41.
    Ehninger A, Trumpp A. The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move. Int J Exp Med. 2011;208:421–8.CrossRefGoogle Scholar
  42. 42.
    Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–54.CrossRefPubMedGoogle Scholar
  43. 43.
    Siegel N, Rosner M, Hanneder M, Freilinger A, Hengstschläger M. Human amniotic fluid stem cells: a new perspective. Amino Acids. 2008;35:291–3.CrossRefPubMedGoogle Scholar
  44. 44.
    Fraser ST, Baron MH. Embryonic fates for extraembryonic lineages: new perspectives. J Cell Biochem. 2009;107:586–91.CrossRefPubMedGoogle Scholar
  45. 45.
    Ueno H, Weisman IL. The origin and fate of yolk sac hematopoiesis: application of chimera analysis to developmental studies. Int J Dev Biol. 2010;54:1019–31.CrossRefPubMedGoogle Scholar
  46. 46.
    Antonucci I, Provenzano M, Rodrigues M, Pantalone A, Salini V, Ballerini P, Borlongan CV, Stuppia L. Amniotic fluid stem cells: a novel source for modeling of human genetic diseases. Int J Mol Sci. 2016;17:E607.CrossRefPubMedGoogle Scholar
  47. 47.
    Frenzel L, Hermine O. Mast cells and inflammation. Joint Bone Spine. 2013;80:141–5.CrossRefPubMedGoogle Scholar
  48. 48.
    Nurden AT. Platelets, inflammation and tissue regeneration. Tromb Haemost. 2011;105(Suppl 1):S13–33.CrossRefGoogle Scholar
  49. 49.
    Yoshida S, Wada Y. Transfer of maternal cholesterol to embryo and fetus in pregnant mice. J Lipid Res. 2005;46:2168–74.CrossRefPubMedGoogle Scholar
  50. 50.
    Miller WL, Bose HS. Early steps in steroidogenesis: Intracellular cholesterol trafficking. J Lipid Res. 2011;5:2111–35.CrossRefGoogle Scholar
  51. 51.
    Gilliver SC. Sex steroids as inflammatory regulators. J Steroid Biochem Mol Biol. 2010;120:105–15.CrossRefPubMedGoogle Scholar
  52. 52.
    Dichlberger A, Kovanen PT, Schneider WJ. Mast cells: from lipid droplets to lipid mediators. Clin Sci. 2013;125:121–30.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Melo RCN, D’Avila H, Wan H-C, Bozza PT, Dvorak AM, Weller PF. Lipid bodies in inflammatory cells: structure, function and current imaging techniques. J Histochem Cytochem. 2011;59:540–6.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Ghesquiere B, Wong BW, Kuchnio A, Carmeliet P. Metabolism of stromal and immune cells in health and disease. Nature 2014;511:167–76.CrossRefPubMedGoogle Scholar
  55. 55.
    Aller MA, Arias JI, Arias J. Pathological axes of wound repair. Gastrulation revisited. Theor Biol Med Model. 2010;7:37.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Boroviak T, Nichols J. Primate embryogenesis predicts the hallmarks of human naïve pluripotency. Development 2017;144:175–86.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Csaba G. Mast cell, the peculiar member of the immune system: a homeostatic aspect. Acta Microbiol Immunol Hung. 2015;63:207–31.CrossRefGoogle Scholar
  58. 58.
    Yokoyama H. Initiation of limb regeneration: the critical step for regenerative capacity. Dev Growth Differ. 2008;50:13–22.CrossRefPubMedGoogle Scholar
  59. 59.
    Khodadi E, Shahrabi S, Shahjahani M, Azandeh S, Saki N. Role of stem cell factor in the placental niche. Cell Tissue Res. 2016;366:523–31.CrossRefPubMedGoogle Scholar
  60. 60.
    Balaji S, Watson CL, Ranjan R, King A, Bollyky PL, Keswani SG. Chemokine involvement in fetal and adult wound healing. Adv Wound Care. 2015;4:660–71.CrossRefGoogle Scholar
  61. 61.
    Latchana N, Peck JR, Whitson B, Black SM. Preservation solutions for cardiac and pulmonary donor grafts: a review of the current literature. J Thorac Dis. 2014;6:1143–9.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Latchana N, Peck JR, Whitson BA, Henry ML, Elkhammas EA, Black SM. Preservation solutions used during abdominal transplantation: current status and outcomes. World J Transpl. 2015;5:154–64.CrossRefGoogle Scholar
  63. 63.
    Nazari M, Ni NC, Lüdke A, Li SH, Guo J, Weisel RD, Li RK. Mast cell promote proliferation and migration and inhibit differentiation of mesenchymal stem cells through PDGF. J Mol Cell Cardiol. 2016;94:32–42.CrossRefPubMedGoogle Scholar
  64. 64.
    Wulff BC, Parent AE, Meleski MA, DiPietro LA, Schrementi ME, Wilgus TA. Mast cells contribute to scar formation during fetal wound healing. J Invest Dermatol. 2012;132:458–65.CrossRefPubMedGoogle Scholar
  65. 65.
    Wilgus TA, Wulff BC. The importance of mast cells in dermal scarring. Adv Wound Care. 2014;3:356–65.CrossRefGoogle Scholar
  66. 66.
    Douaiher J, Succar J, Lancerotto L, Gurish MF, Orgill DP, Hamilton MJ, Krilis SA, Stevens RL. Development of mast cells and importance of their tryptase and chymase serine proteases in inflammation and wound healing. Adv Immunol. 2014;122:211–52.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Sriram G, Bigliardi PL, Bigliardi-Qi M. Fibroblast heterogeneity and its implications for engineering organotypic skin models in vitro. Eur J Cell Biology. 2015;94:483–512.CrossRefGoogle Scholar
  68. 68.
    Flor J. Salamander regeneration as a model for developing novel regenerative and anticancer therapies. J Cancer. 2014;5:715–9.CrossRefGoogle Scholar
  69. 69.
    Redd MJ, Cooper L, Wood W, Stramer B, Martin P. Wound healing and inflammation: embryos reveal the way to perfect repair. Phil Trans R Soc Lond B. 2004;339:777–84.CrossRefGoogle Scholar
  70. 70.
    Motegi S-I, Ishikawa O. Mesenchymal stem cells: The roles and functions in cutaneous wound healing and tumor growth. J Dermatol Sci. 2016;1811:30721–6.Google Scholar
  71. 71.
    Otero-Viñas M, Falanga V. Mesenchymal stem cells in chronic wounds: the spectrum from basic to advanced therapy. Adv Wound Care. 2016;5:149–63.CrossRefGoogle Scholar
  72. 72.
    Theoharides TC, Kempuraj D, Tagen M, Vasiadi M, Centrulo CL. Human umbilical cord blood-derived mast cells. A unique model for the study of neuro-immuno-endocrine interactions. Stem Cell Rev. 2006;6:143–54.Google Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Maria-Angeles Aller
    • 1
  • Natalia Arias
    • 2
    • 3
  • Vicente Martínez
    • 4
  • Patri Vergara
    • 4
    • 5
  • Jaime Arias
    • 1
  1. 1.Department of Surgery, School of MedicineComplutense University of MadridMadridSpain
  2. 2.UCL Division of MedicineInstitute for Liver and Digestive HealthLondonUK
  3. 3.INEUROPA, Instituto de Neurociencias del Principado de AsturiasOviedoSpain
  4. 4.Department of Cell Biology, Physiology and Immunology, Veterinary SchoolAutonoma University of BarcelonaBarcelonaSpain
  5. 5.Biomedical Research Center for Hepatic and Digestive Illnesses (CIBERehd)Carlos II Health InstituteBarcelonaSpain

Personalised recommendations