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Vasc Cell. 2014 Nov 01;6:22. doi: 10.1186/2045-824X-6-22. eCollection 2014.

Lymphangiogenesis and angiogenesis during human fetal pancreas development.

Vascular cell

Matthias S Roost, Liesbeth van Iperen, Ana de Melo Bernardo, Christine L Mummery, Françoise Carlotti, Eelco Jp de Koning, Susana M Chuva de Sousa Lopes

Affiliations

  1. Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.
  2. Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
  3. Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands ; Hubrecht Institute for Developmental Biology and Stem Cell Research, University Medical Center, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
  4. Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands ; Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.

PMID: 25785186 PMCID: PMC4362646 DOI: 10.1186/2045-824X-6-22

Abstract

BACKGROUND: The complex endocrine and exocrine functionality of the human pancreas depends on an efficient fluid transport through the blood and the lymphatic vascular systems. The lymphatic vasculature has key roles in the physiology of the pancreas and in regulating the immune response, both important for developing successful transplantation and cell-replacement therapies to treat diabetes. However, little is known about how the lymphatic and blood systems develop in humans. Here, we investigated the establishment of these two vascular systems in human pancreas organogenesis in order to understand neovascularization in the context of emerging regenerative therapies.

METHODS: We examined angiogenesis and lymphangiogenesis during human pancreas development between 9 and 22 weeks of gestation (W9-W22) by immunohistochemistry.

RESULTS: As early as W9, the peri-pancreatic mesenchyme was populated by CD31-expressing blood vessels as well as LYVE1- and PDPN-expressing lymphatic vessels. The appearance of smooth muscle cell-coated blood vessels in the intra-pancreatic mesenchyme occurred only several weeks later and from W14.5 onwards the islets of Langerhans also became heavily irrigated by blood vessels. In contrast to blood vessels, LYVE1- and PDPN-expressing lymphatic vessels were restricted to the peri-pancreatic mesenchyme until later in development (W14.5-W17), and some of these invading lymphatic vessels contained smooth muscle cells at W17. Interestingly, between W11-W22, most large caliber lymphatic vessels were lined with a characteristic, discontinuous, collagen type IV-rich basement membrane. Whilst lymphatic vessels did not directly intrude the islets of Langerhans, three-dimensional reconstruction revealed that they were present in the vicinity of islets of Langerhans between W17-W22.

CONCLUSION: Our data suggest that the blood and lymphatic machinery in the human pancreas is in place to support endocrine function from W17-W22 onwards. Our study provides the first systematic assessment of the progression of lymphangiogenesis during human pancreatic development.

Keywords: Angiogenesis; Fetal development; Human; Lymphangiogenesis; Pancreas

References

  1. Genome Med. 2011 Sep 27;3(9):61 - PubMed
  2. Diabetes. 2000 Feb;49(2):225-32 - PubMed
  3. J Histochem Cytochem. 1998 Feb;46(2):165-76 - PubMed
  4. J Transplant. 2011;2011:892453 - PubMed
  5. J Biol Chem. 2008 Feb 15;283(7):3942-50 - PubMed
  6. Ann Transplant. 1997;2(3):46-54 - PubMed
  7. Cell Tissue Res. 2009 Jan;335(1):97-108 - PubMed
  8. Cell Mol Life Sci. 2007 Aug;64(15):1915-29 - PubMed
  9. Mech Dev. 2002 Aug;116(1-2):223-6 - PubMed
  10. PLoS One. 2013 Aug 12;8(8):e72513 - PubMed
  11. Gene. 2013 Apr 15;518(2):246-55 - PubMed
  12. Clin Cancer Res. 2004 Oct 15;10(20):6919-28 - PubMed
  13. Diabetologia. 1982 Nov;23(5):426-30 - PubMed
  14. Cold Spring Harb Perspect Med. 2012 Apr;2(4):a006445 - PubMed
  15. Adv Anat Pathol. 2012 Sep;19(5):281-95 - PubMed
  16. J Cell Biol. 2009 May 4;185(3):439-57 - PubMed
  17. Science. 1999 May 28;284(5419):1534-7 - PubMed
  18. Diabetologia. 2012 Feb;55(2):372-81 - PubMed
  19. Nat Biotechnol. 2006 Nov;24(11):1392-401 - PubMed
  20. Trends Cardiovasc Med. 2003 Jan;13(1):1-7 - PubMed
  21. Nat Rev Immunol. 2012 Nov;12(11):762-73 - PubMed
  22. Arch Dis Child. 1973 Feb;48(2):151-2 - PubMed
  23. PLoS One. 2009 Dec 09;4(12 ):e8234 - PubMed
  24. Diabetes. 2013 Oct;62(10):3514-22 - PubMed
  25. Nature. 2010 Apr 29;464(7293):1293-300 - PubMed
  26. Clin Anat. 2009 Sep;22(6):716-29 - PubMed
  27. J Histochem Cytochem. 2006 Apr;54(4):385-95 - PubMed
  28. Diabetes. 1988 Mar;37(3):286-91 - PubMed
  29. Angiogenesis. 2008;11(1):79-89 - PubMed
  30. Vasc Cell. 2012 Sep 03;4(1):15 - PubMed
  31. J Endocrinol. 1972 Mar;52(3):497-505 - PubMed
  32. J Anat. 2010 Jun;216(6):671-82 - PubMed
  33. Diabetes. 2005 Jul;54(7):2080-9 - PubMed
  34. Diabetologia. 2008 Jul;51(7):1169-80 - PubMed
  35. J Clin Invest. 1967 Jun;46(6):903-10 - PubMed
  36. Curr Biol. 2003 Jun 17;13(12):1070-4 - PubMed
  37. Dev Dyn. 2006 Jun;235(6):1554-62 - PubMed
  38. J Histochem Cytochem. 2009 Sep;57(9):811-24 - PubMed
  39. Dev Dyn. 2011 Mar;240(3):530-65 - PubMed
  40. Am J Pathol. 1995 Feb;146(2):429-35 - PubMed
  41. Diabetologia. 2008 Feb;51(2):285-97 - PubMed
  42. BMC Dev Biol. 2008 Apr 22;8:43 - PubMed
  43. World J Surg. 2007 Apr;31(4):705-14 - PubMed
  44. Nat Biotechnol. 2008 Apr;26(4):443-52 - PubMed
  45. J Endocrinol. 2004 Apr;181(1):11-23 - PubMed
  46. Cell. 1996 Dec 27;87(7):1153-5 - PubMed
  47. Diabetes. 2012 Aug;61(8):2016-29 - PubMed
  48. Nat Rev Mol Cell Biol. 2007 Jun;8(6):464-78 - PubMed
  49. Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5222-9 - PubMed
  50. Science. 2001 Oct 19;294(5542):564-7 - PubMed
  51. J Clin Endocrinol Metab. 2010 Mar;95(3):1034-43 - PubMed
  52. Cell Transplant. 2012;21(6):1305-20 - PubMed
  53. J Cell Biol. 2012 Jun 11;197(6):837-49 - PubMed
  54. Cell. 2010 Feb 19;140(4):460-76 - PubMed
  55. Diabetes. 2004 May;53(5):1318-25 - PubMed
  56. Histochem Cell Biol. 2008 Dec;130(6):1063-78 - PubMed
  57. J Clin Endocrinol Metab. 2012 Sep;97(9):3197-206 - PubMed
  58. Mol Aspects Med. 2011 Apr;32(2):146-58 - PubMed
  59. Diabetologia. 2002 Jun;45(6):749-63 - PubMed
  60. Microsc Res Tech. 1997 Jun 1-15;37(5-6):456-77 - PubMed

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