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
Affiliations
- Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.
- Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
- 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.
- 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
- Genome Med. 2011 Sep 27;3(9):61 - PubMed
- Diabetes. 2000 Feb;49(2):225-32 - PubMed
- J Histochem Cytochem. 1998 Feb;46(2):165-76 - PubMed
- J Transplant. 2011;2011:892453 - PubMed
- J Biol Chem. 2008 Feb 15;283(7):3942-50 - PubMed
- Ann Transplant. 1997;2(3):46-54 - PubMed
- Cell Tissue Res. 2009 Jan;335(1):97-108 - PubMed
- Cell Mol Life Sci. 2007 Aug;64(15):1915-29 - PubMed
- Mech Dev. 2002 Aug;116(1-2):223-6 - PubMed
- PLoS One. 2013 Aug 12;8(8):e72513 - PubMed
- Gene. 2013 Apr 15;518(2):246-55 - PubMed
- Clin Cancer Res. 2004 Oct 15;10(20):6919-28 - PubMed
- Diabetologia. 1982 Nov;23(5):426-30 - PubMed
- Cold Spring Harb Perspect Med. 2012 Apr;2(4):a006445 - PubMed
- Adv Anat Pathol. 2012 Sep;19(5):281-95 - PubMed
- J Cell Biol. 2009 May 4;185(3):439-57 - PubMed
- Science. 1999 May 28;284(5419):1534-7 - PubMed
- Diabetologia. 2012 Feb;55(2):372-81 - PubMed
- Nat Biotechnol. 2006 Nov;24(11):1392-401 - PubMed
- Trends Cardiovasc Med. 2003 Jan;13(1):1-7 - PubMed
- Nat Rev Immunol. 2012 Nov;12(11):762-73 - PubMed
- Arch Dis Child. 1973 Feb;48(2):151-2 - PubMed
- PLoS One. 2009 Dec 09;4(12 ):e8234 - PubMed
- Diabetes. 2013 Oct;62(10):3514-22 - PubMed
- Nature. 2010 Apr 29;464(7293):1293-300 - PubMed
- Clin Anat. 2009 Sep;22(6):716-29 - PubMed
- J Histochem Cytochem. 2006 Apr;54(4):385-95 - PubMed
- Diabetes. 1988 Mar;37(3):286-91 - PubMed
- Angiogenesis. 2008;11(1):79-89 - PubMed
- Vasc Cell. 2012 Sep 03;4(1):15 - PubMed
- J Endocrinol. 1972 Mar;52(3):497-505 - PubMed
- J Anat. 2010 Jun;216(6):671-82 - PubMed
- Diabetes. 2005 Jul;54(7):2080-9 - PubMed
- Diabetologia. 2008 Jul;51(7):1169-80 - PubMed
- J Clin Invest. 1967 Jun;46(6):903-10 - PubMed
- Curr Biol. 2003 Jun 17;13(12):1070-4 - PubMed
- Dev Dyn. 2006 Jun;235(6):1554-62 - PubMed
- J Histochem Cytochem. 2009 Sep;57(9):811-24 - PubMed
- Dev Dyn. 2011 Mar;240(3):530-65 - PubMed
- Am J Pathol. 1995 Feb;146(2):429-35 - PubMed
- Diabetologia. 2008 Feb;51(2):285-97 - PubMed
- BMC Dev Biol. 2008 Apr 22;8:43 - PubMed
- World J Surg. 2007 Apr;31(4):705-14 - PubMed
- Nat Biotechnol. 2008 Apr;26(4):443-52 - PubMed
- J Endocrinol. 2004 Apr;181(1):11-23 - PubMed
- Cell. 1996 Dec 27;87(7):1153-5 - PubMed
- Diabetes. 2012 Aug;61(8):2016-29 - PubMed
- Nat Rev Mol Cell Biol. 2007 Jun;8(6):464-78 - PubMed
- Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5222-9 - PubMed
- Science. 2001 Oct 19;294(5542):564-7 - PubMed
- J Clin Endocrinol Metab. 2010 Mar;95(3):1034-43 - PubMed
- Cell Transplant. 2012;21(6):1305-20 - PubMed
- J Cell Biol. 2012 Jun 11;197(6):837-49 - PubMed
- Cell. 2010 Feb 19;140(4):460-76 - PubMed
- Diabetes. 2004 May;53(5):1318-25 - PubMed
- Histochem Cell Biol. 2008 Dec;130(6):1063-78 - PubMed
- J Clin Endocrinol Metab. 2012 Sep;97(9):3197-206 - PubMed
- Mol Aspects Med. 2011 Apr;32(2):146-58 - PubMed
- Diabetologia. 2002 Jun;45(6):749-63 - PubMed
- Microsc Res Tech. 1997 Jun 1-15;37(5-6):456-77 - PubMed
Publication Types