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Lymphangiogenesis and angiogenesis during human fetal pancreas development.

Roost MS, van Iperen L, de Melo Bernardo A, Mummery CL, Carlotti F, de Koning EJ, Chuva de Sousa Lopes SM - (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus

Model of the progression of lymphangiogenesis and angiogenesis during human pancreatic development. Cartoon illustrating the progression of lymphangiogenesis (top) and angiogenesis (bottom) showing the timing of invasion, formation of a COL4A-rich basement membrane (BM) and the association with smooth muscle cells (SMCs) in the peri-pancreatic mesenchyme (PPM) and intra-pancreatic mesenchyme (IPM) between W9 and W22.
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Fig6: Model of the progression of lymphangiogenesis and angiogenesis during human pancreatic development. Cartoon illustrating the progression of lymphangiogenesis (top) and angiogenesis (bottom) showing the timing of invasion, formation of a COL4A-rich basement membrane (BM) and the association with smooth muscle cells (SMCs) in the peri-pancreatic mesenchyme (PPM) and intra-pancreatic mesenchyme (IPM) between W9 and W22.

Mentions: During pancreas development, lymphangiogenesis occurred rather gradually in the PPM, with invasion at W9, deposition of basement membrane around W11 and coating by smooth muscle cells at W14.5; in the IPM, however, all steps occurred almost simultaneously within 3 weeks, between W14.5-W17 (FigureĀ 6).Figure 6


Lymphangiogenesis and angiogenesis during human fetal pancreas development.

Roost MS, van Iperen L, de Melo Bernardo A, Mummery CL, Carlotti F, de Koning EJ, Chuva de Sousa Lopes SM - (2014)

Model of the progression of lymphangiogenesis and angiogenesis during human pancreatic development. Cartoon illustrating the progression of lymphangiogenesis (top) and angiogenesis (bottom) showing the timing of invasion, formation of a COL4A-rich basement membrane (BM) and the association with smooth muscle cells (SMCs) in the peri-pancreatic mesenchyme (PPM) and intra-pancreatic mesenchyme (IPM) between W9 and W22.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4362646&req=5

Fig6: Model of the progression of lymphangiogenesis and angiogenesis during human pancreatic development. Cartoon illustrating the progression of lymphangiogenesis (top) and angiogenesis (bottom) showing the timing of invasion, formation of a COL4A-rich basement membrane (BM) and the association with smooth muscle cells (SMCs) in the peri-pancreatic mesenchyme (PPM) and intra-pancreatic mesenchyme (IPM) between W9 and W22.
Mentions: During pancreas development, lymphangiogenesis occurred rather gradually in the PPM, with invasion at W9, deposition of basement membrane around W11 and coating by smooth muscle cells at W14.5; in the IPM, however, all steps occurred almost simultaneously within 3 weeks, between W14.5-W17 (FigureĀ 6).Figure 6

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus