The peritoneum as a natural scaffold for vascular regeneration

14Citations
Citations of this article
34Readers
Mendeley users who have this article in their library.

Abstract

Objective: The peritoneum has the same developmental origin as blood vessels, is highly reactive and poorly thrombogenic. We hypothesize that parietal peritoneum can sustain development and regeneration of new vessels. Methods and Results: The study comprised two experimental approaches. First, to test surgical feasibility and efficacy of the peritoneal vascular autograft, we set up an autologous transplantation procedure in pigs, where a tubularized parietal peritoneal graft was covered with a metal mesh and anastomosed end-to-end in the infrarenal aorta. Second, to dissect the contribution of graft vs host cells to the newly developed vessel wall, we performed human-to-rat peritoneal patch grafting in the abdominal aorta and examined the origin of endothelial and smooth muscle cells. In pig experiments, the graft remodeled to an apparently normal blood vessel, without thrombosis. Histology confirmed arterialization of the graft with complete endothelial coverage and neointimal hyperplasia in the absence of erosion, inflammation or thrombosis. In rats, immunostaining for human mitochondri revealed that endothelial cells and smooth muscle cells rarely were of human origin. Remodeling of the graft was mainly attributable to local cells with no clear evidence of c-kit+ endothelial progenitor cells or c-kit+ resident perivascular progenitor cells. Conclusions: The parietal peritoneum can be feasibly used as a scaffold to sustain the regeneration of blood vessels, which appears to occur through the contribution of host-derived resident mature cells. © 2012 Bonvini et al.

Figures

  • Figure 1. Graphic representation of the two types of experiments. A) A pig autologous end-to-end peritoneal implant was used to study patency, eventual thrombosis, endothelization and arterializations of the graft, 2 weeks after surgery. B) A human-to-rat peritoneal graft approach was set up to study remodeling of the peritoneum and to determine the host vs donor origin of cells that contributed to the process of endothelization and eventual arterialization. doi:10.1371/journal.pone.0033557.g001
  • Figure 2. Macroscopic representation of graft preparation, implantation and removal in pigs. A–B) Tailoring of the peritoneal graft on a tutor. C) Coverage of the peritoneal graft with the metal mesh. D) Proximal anastomosis showing the adhesion of the peritoneum to the metal mesh when pulsatile flow is established into the graft. E) Graft harvested (A, native aorta; P, peritoenal graft) with no signs of overt dilatation. F) Fresh transversal equatorial cut of the peritoneal graft showing patency and (G) thickening of the peritoneal graft at 15 days from the implant. H) Intraluminal appearance at the proximal anastomosis (A, native aorta; P, peritoenum graft). Scale bars 1 cm. doi:10.1371/journal.pone.0033557.g002
  • Figure 3. Histopathological analysis of the peritoneal patch explanted from pigs. Peritoneal graft pre-innestum (A), native aorta (B, C) and graft after two weeks (D–J). A) normal peritoneum, double staining with alfa-SMA (blue) and elastic von Gieson (black-brown) magnification 806, scale bar 40 mm. B) native aorta, double staining showing the media with elastic fibres in black and smooth muscle cells in blue, magnification 506, scale bar 50 mm. C) Native aorta, von Willebrand factor staining of the endothelium, magnification 1606, scale bar 20 mm. D) Graft and metallic scaffold (arrows indicate some of the holes around the graft), magnification 12,56, scale bar 250 mm. E) graft remodeling, magnification 316scale bar 100 mm. F) Arterialization of graft, magnification 62,56, scale bar 50 mm. G) Intimal hyperplasia, magnification 1256, scale bar 25 mm. H, I) Endothelization of the graft, von Willebrand factor staining magnification 1606 (scale bar 20 mm) and 3206 (scale bar 10 mm), respectively. doi:10.1371/journal.pone.0033557.g003
  • Figure 4. Histopathological analysis of the aortic peritoneal patch explanted from rats. Sections of the native aorta (top panels) and the patched aorta (middle panels and details in the bottom panels), were stained with hematoxylin and eosin, Masson’s trichrome and using immunofluorescence for endothelium (vWf) and smooth muscle cells (alpha-SMA). The peritoneal patch (at the top) was covered by an endothelial layer, but there was no tunica media (red staining). Compared with the native aorta, the transversal sections containing the peritoneal patch showed extensive thickening, formed by a densely cellular reactive tissue. Detail panels in the bottom of the figure show that such tissue contained elongated cells, collagen, as well as capillaries and arterioles. doi:10.1371/journal.pone.0033557.g004
  • Figure 5. Origin of peritoneal patch remodeling cells. The remodeled patch developed as a new artery wall, with an endothelial layer. We asked whether cells that contributed to patch remodeling were of host (rat) or peritoneal (human) origin, by double staining with vWf (green in B–F) or alpha-SMA (green in H–M)) and human mitochondri (red). A–C) Within the densely cellulated reactive tissue that thickened the peritoneal patch, a few capillary-lining endothelial cells (green in B) were of human origin (red, higher magnification in panel C). D–F) Within the neo-formed endothelial layer (green in E), some cells (red in D) were of human origin (higher magnification in panel F). G–J) In the remodeled patch tissue, rare alpha-SMA staining cells (green in H and J) co-stained with human mitochondri (red). K–M) The same was in the close vicinity of the native aorta-peritoneal patch junction, where a medial smooth muscle layer (green in K, L) is still present. doi:10.1371/journal.pone.0033557.g005
  • Figure 6. Progenitor cell markers in normal and patched aortic sections. A–C) Aortic sections including the peritoneal patch (C, scale bar 500 mm) were co-stained for c-kit and CD140b, also known as PDGFRB (A, scale bar 100 mm), or c-kit and NG2 (B, scale bar 100 mm). Panel D (scale bar 100 mm) shows c-kit staining of an endothelial area overlying the peritoneal patch (scale bar 100 mm). Panel E shows c-kit staining in a section of a normal aorta (scale bar 100 mm). In panel D and E, there is no c-kit signal from nucleated cells above the green background attributable to elastic fibers autofluorescence. doi:10.1371/journal.pone.0033557.g006

References Powered by Scopus

Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization

2234Citations
N/AReaders
Get full text

Human adult vena saphena contains perivascular progenitor cells endowed with clonogenic and proangiogenic potential

260Citations
N/AReaders
Get full text

Novel vascular graft grown within recipient's own peritoneal cavity

258Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Bovine invitro reproduction models can contribute to the development of (female) fertility preservation strategies

33Citations
N/AReaders
Get full text

Enhanced vascular biocompatibility of decellularized xeno-/allogeneic matrices in a rodent model

26Citations
N/AReaders
Get full text

RESEARCH ARTICLE Modulating electrospun polycaprolactone scaffold morphology and composition to alter endothelial cell proliferation and angiogenic gene response

22Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Bonvini, S., Albiero, M., Ferretto, L., Angelini, A., Battocchio, P., Fedrigo, M., … Grego, F. (2012). The peritoneum as a natural scaffold for vascular regeneration. PLoS ONE, 7(3). https://doi.org/10.1371/journal.pone.0033557

Readers over time

‘13‘14‘16‘17‘18‘19‘20‘21‘22‘2402468

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 14

64%

Professor / Associate Prof. 6

27%

Researcher 2

9%

Readers' Discipline

Tooltip

Medicine and Dentistry 12

52%

Biochemistry, Genetics and Molecular Bi... 5

22%

Engineering 4

17%

Agricultural and Biological Sciences 2

9%

Save time finding and organizing research with Mendeley

Sign up for free
0