Patterns of Neointima Formation After Coil or Stent Treatment in a Rat Saccular Sidewall Aneurysm Model.


Journal

Stroke
ISSN: 1524-4628
Titre abrégé: Stroke
Pays: United States
ID NLM: 0235266

Informations de publication

Date de publication:
03 2021
Historique:
pubmed: 29 1 2021
medline: 15 12 2021
entrez: 28 1 2021
Statut: ppublish

Résumé

Endovascular aneurysm treatment relies on a biological process, including cell migration for thrombus organization and growth of a neointima. To better understand aneurysm healing, our study explores the origin of neointima-forming and thrombus-organizing cells in a rat saccular sidewall aneurysm model. Saccular aneurysms were transplanted onto the abdominal aorta of male Lewis rats and endovascularly treated with coils (n=28) or stents (n=26). In 34 cases, GFP+ (green fluorescent protein)-expressing vital aneurysms were sutured on wild-type rats, and in 23 cases, decellularized wild-type aneurysms were sutured on GFP+ rats. Follow-up at 3, 7, 14, 21, and 28 days evaluated aneurysms by fluorescence angiography, macroscopic inspection, and microscopy for healing and inflammation status. Furthermore, the origin of cells was tracked with fluorescence histology. In animals with successful functional healing, histological studies showed a gradually advancing thrombus organization over time characterized by progressively growing neointima from the periphery of the aneurysm toward the center. Cell counts revealed similar distributions of GFP+ cells for coil or stent treatment in the aneurysm wall (54.4% versus 48.7%) and inside the thrombus (20.5% versus 20.2%) but significantly more GFP+ cells in the neointima of coiled (27.2 %) than stented aneurysms (10.4%; Neointima formation and thrombus organization are concurrent processes during aneurysm healing. Thrombus-organizing cells originate predominantly in the parent artery. Neointima formation relies more on cell migration from the aneurysm wall in coiled aneurysms but receives greater contributions from cells originating in the parent artery in stent-treated aneurysms. Cell migration, which allows for a continuous endothelial lining along the parent artery's lumen, may be a prerequisite for complete aneurysm healing after endovascular therapy. In terms of translation into clinical practice, these findings may explain the variability in achieving complete aneurysm healing after coil treatment and the improved healing rate in stent-assisted coiling.

Sections du résumé

BACKGROUND AND PURPOSE
Endovascular aneurysm treatment relies on a biological process, including cell migration for thrombus organization and growth of a neointima. To better understand aneurysm healing, our study explores the origin of neointima-forming and thrombus-organizing cells in a rat saccular sidewall aneurysm model.
METHODS
Saccular aneurysms were transplanted onto the abdominal aorta of male Lewis rats and endovascularly treated with coils (n=28) or stents (n=26). In 34 cases, GFP+ (green fluorescent protein)-expressing vital aneurysms were sutured on wild-type rats, and in 23 cases, decellularized wild-type aneurysms were sutured on GFP+ rats. Follow-up at 3, 7, 14, 21, and 28 days evaluated aneurysms by fluorescence angiography, macroscopic inspection, and microscopy for healing and inflammation status. Furthermore, the origin of cells was tracked with fluorescence histology.
RESULTS
In animals with successful functional healing, histological studies showed a gradually advancing thrombus organization over time characterized by progressively growing neointima from the periphery of the aneurysm toward the center. Cell counts revealed similar distributions of GFP+ cells for coil or stent treatment in the aneurysm wall (54.4% versus 48.7%) and inside the thrombus (20.5% versus 20.2%) but significantly more GFP+ cells in the neointima of coiled (27.2 %) than stented aneurysms (10.4%;
CONCLUSIONS
Neointima formation and thrombus organization are concurrent processes during aneurysm healing. Thrombus-organizing cells originate predominantly in the parent artery. Neointima formation relies more on cell migration from the aneurysm wall in coiled aneurysms but receives greater contributions from cells originating in the parent artery in stent-treated aneurysms. Cell migration, which allows for a continuous endothelial lining along the parent artery's lumen, may be a prerequisite for complete aneurysm healing after endovascular therapy. In terms of translation into clinical practice, these findings may explain the variability in achieving complete aneurysm healing after coil treatment and the improved healing rate in stent-assisted coiling.

Identifiants

pubmed: 33504186
doi: 10.1161/STROKEAHA.120.032255
doi:

Substances chimiques

Green Fluorescent Proteins 147336-22-9

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1043-1052

Auteurs

Basil E Grüter (BE)

Department of Neurosurgery (B.E.G., S.W., F.S., G.B., L.A., E.N., D.C., J.F., S.M.), Kantonsspital Aarau, Switzerland.
Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.

Stefan Wanderer (S)

Department of Neurosurgery (B.E.G., S.W., F.S., G.B., L.A., E.N., D.C., J.F., S.M.), Kantonsspital Aarau, Switzerland.
Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.

Fabio Strange (F)

Department of Neurosurgery (B.E.G., S.W., F.S., G.B., L.A., E.N., D.C., J.F., S.M.), Kantonsspital Aarau, Switzerland.
Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.

Gwendoline Boillat (G)

Department of Neurosurgery (B.E.G., S.W., F.S., G.B., L.A., E.N., D.C., J.F., S.M.), Kantonsspital Aarau, Switzerland.
Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.

Dominik Täschler (D)

Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.

Jeannine Rey (J)

Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.

Davide M Croci (DM)

Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.

Denis Grandgirard (D)

Neuroinfection Laboratory, Institute for Infectious Diseases (D.G., S.L.L.), University of Bern, Switzerland.
Cluster for Regenerative Neuroscience, Department for BioMedical Research (D.G., S.L.L., S.D.S., H.R.W.), University of Bern, Switzerland.

Stephen L Leib (SL)

Neuroinfection Laboratory, Institute for Infectious Diseases (D.G., S.L.L.), University of Bern, Switzerland.
Cluster for Regenerative Neuroscience, Department for BioMedical Research (D.G., S.L.L., S.D.S., H.R.W.), University of Bern, Switzerland.

Michael von Gunten (M)

Institute of Pathology Laenggasse, Ittigen, Switzerland (M.v.G.).

Stefano Di Santo (S)

Cluster for Regenerative Neuroscience, Department for BioMedical Research (D.G., S.L.L., S.D.S., H.R.W.), University of Bern, Switzerland.
Department of Neurosurgery, Bern University Hospital, Inselspital Bern, Switzerland (S.D.S., H.R.W.).

Hans Rudolf Widmer (HR)

Cluster for Regenerative Neuroscience, Department for BioMedical Research (D.G., S.L.L., S.D.S., H.R.W.), University of Bern, Switzerland.
Department of Neurosurgery, Bern University Hospital, Inselspital Bern, Switzerland (S.D.S., H.R.W.).

Luca Remonda (L)

Division of Neuroradiology, Department of Radiology (L.R.), Kantonsspital Aarau, Switzerland.

Lukas Andereggen (L)

Department of Neurosurgery (B.E.G., S.W., F.S., G.B., L.A., E.N., D.C., J.F., S.M.), Kantonsspital Aarau, Switzerland.
Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.

Edin Nevzati (E)

Department of Neurosurgery (B.E.G., S.W., F.S., G.B., L.A., E.N., D.C., J.F., S.M.), Kantonsspital Aarau, Switzerland.
Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.

Daniel Coluccia (D)

Department of Neurosurgery (B.E.G., S.W., F.S., G.B., L.A., E.N., D.C., J.F., S.M.), Kantonsspital Aarau, Switzerland.
Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.

Javier Fandino (J)

Department of Neurosurgery (B.E.G., S.W., F.S., G.B., L.A., E.N., D.C., J.F., S.M.), Kantonsspital Aarau, Switzerland.
Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.

Serge Marbacher (S)

Department of Neurosurgery (B.E.G., S.W., F.S., G.B., L.A., E.N., D.C., J.F., S.M.), Kantonsspital Aarau, Switzerland.
Cerebrovascular Research Group, Department for BioMedical Research (B.E.G., S.W., F.S., G.B., D.T., J.R., D.M.C., L.A., E.N., D.C., J.F., S.M.), University of Bern, Switzerland.

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