Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular injury in a porcine model
Objective High restenosis rates are a limitation of peripheral vascular interventions. Previous studies have shown that surgical implantation of a tissue-engineered endothelium onto the adventitia surface of injured vessels regulates vascular repair. In the present study, we developed a particulate...
| Main Authors: | , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2016
|
| Online Access: | http://hdl.handle.net/1721.1/102309 https://orcid.org/0000-0002-7832-7156 |
| _version_ | 1826197797074894848 |
|---|---|
| author | Nugent, Helen M. Ng, Yin-Shan White, Desmond Groothius, Adam Kanner, Glenn Edelman, Elazer R. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Nugent, Helen M. Ng, Yin-Shan White, Desmond Groothius, Adam Kanner, Glenn Edelman, Elazer R. |
| author_sort | Nugent, Helen M. |
| collection | MIT |
| description | Objective
High restenosis rates are a limitation of peripheral vascular interventions. Previous studies have shown that surgical implantation of a tissue-engineered endothelium onto the adventitia surface of injured vessels regulates vascular repair. In the present study, we developed a particulate formulation of tissue-engineered endothelium and a method to deliver the formulation perivascular to injured blood vessels using a percutaneous, minimally invasive technique.
Methods
Stainless steel stents were implanted in 18 balloon-injured femoral arteries of nine domestic swine, followed by ultrasound-guided percutaneous perivascular injection of gelatin particles containing cultured allogeneic porcine aortic endothelial cells (PAE). Controls received injections of empty particles (matrix) or no perivascular injection (sham) after stent deployment. Animals were sacrificed after 90 days.
Results
Angiographic analysis revealed a significantly greater lumen diameter in the stented segments of arteries treated with PAE/matrix (4.72 ± 0.12 mm) compared with matrix (4.01 ± 0.20 mm) or sham (4.03 ± 0.16 mm) controls (P < .05). Similarly, histologic analysis revealed that PAE/matrix-treated arteries had the greatest lumen area (20.4 ± 0.7 mm[superscript 2]; P < .05) compared with controls (16.1 ± 0.9 mm[superscript 2] and 17.1 ± 1.0 mm[superscript 2] for sham and matrix controls, respectively) and the smallest intimal area (3.3 ± 0.4 mm[superscript 2]; P < .05) compared with controls (6.2 ± 0.5 mm[superscript 2] and 4.4 ± 0.5 mm[superscript 2] for sham and matrix controls, respectively). Overall, PAE-treated arteries had a 33% to 50% decrease in percent occlusion (P < .05) compared with controls. Histopathological analysis revealed fewer leukocytes present in the intima in the PAE/matrix group compared with control groups, suggesting that the biological effects were in part due to inhibition of the inflammatory phase of the vascular response to injury.
Conclusions
Minimally invasive, perivascular delivery of PAE/matrix to stented arteries was performed safely using ultrasound-guided percutaneous injections and significantly decreased stenosis. Application at the time of or subsequent to peripheral interventions may decrease clinical restenosis rates. |
| first_indexed | 2024-09-23T10:53:36Z |
| format | Article |
| id | mit-1721.1/102309 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:53:36Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1023092022-09-27T15:47:37Z Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular injury in a porcine model Nugent, Helen M. Ng, Yin-Shan White, Desmond Groothius, Adam Kanner, Glenn Edelman, Elazer R. Harvard University--MIT Division of Health Sciences and Technology Nugent, Helen M. Groothius, Adam Edelman, Elazer R. Objective High restenosis rates are a limitation of peripheral vascular interventions. Previous studies have shown that surgical implantation of a tissue-engineered endothelium onto the adventitia surface of injured vessels regulates vascular repair. In the present study, we developed a particulate formulation of tissue-engineered endothelium and a method to deliver the formulation perivascular to injured blood vessels using a percutaneous, minimally invasive technique. Methods Stainless steel stents were implanted in 18 balloon-injured femoral arteries of nine domestic swine, followed by ultrasound-guided percutaneous perivascular injection of gelatin particles containing cultured allogeneic porcine aortic endothelial cells (PAE). Controls received injections of empty particles (matrix) or no perivascular injection (sham) after stent deployment. Animals were sacrificed after 90 days. Results Angiographic analysis revealed a significantly greater lumen diameter in the stented segments of arteries treated with PAE/matrix (4.72 ± 0.12 mm) compared with matrix (4.01 ± 0.20 mm) or sham (4.03 ± 0.16 mm) controls (P < .05). Similarly, histologic analysis revealed that PAE/matrix-treated arteries had the greatest lumen area (20.4 ± 0.7 mm[superscript 2]; P < .05) compared with controls (16.1 ± 0.9 mm[superscript 2] and 17.1 ± 1.0 mm[superscript 2] for sham and matrix controls, respectively) and the smallest intimal area (3.3 ± 0.4 mm[superscript 2]; P < .05) compared with controls (6.2 ± 0.5 mm[superscript 2] and 4.4 ± 0.5 mm[superscript 2] for sham and matrix controls, respectively). Overall, PAE-treated arteries had a 33% to 50% decrease in percent occlusion (P < .05) compared with controls. Histopathological analysis revealed fewer leukocytes present in the intima in the PAE/matrix group compared with control groups, suggesting that the biological effects were in part due to inhibition of the inflammatory phase of the vascular response to injury. Conclusions Minimally invasive, perivascular delivery of PAE/matrix to stented arteries was performed safely using ultrasound-guided percutaneous injections and significantly decreased stenosis. Application at the time of or subsequent to peripheral interventions may decrease clinical restenosis rates. 2016-04-28T13:07:53Z 2016-04-28T13:07:53Z 2012-07 2011-12 Article http://purl.org/eprint/type/JournalArticle 07415214 http://hdl.handle.net/1721.1/102309 Nugent, Helen M., Yin-Shan Ng, Desmond White, Adam Groothius, Glenn Kanner, and Elazer R. Edelman. “Ultrasound-Guided Percutaneous Delivery of Tissue-Engineered Endothelial Cells to the Adventitia of Stented Arteries Controls the Response to Vascular Injury in a Porcine Model.” Journal of Vascular Surgery 56, no. 4 (October 2012): 1078–1088. https://orcid.org/0000-0002-7832-7156 en_US http://dx.doi.org/10.1016/j.jvs.2012.03.002 Journal of Vascular Surgery Creative Commons Attribution-Noncommercial-NoDerivatives http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Nugent, Helen M. Ng, Yin-Shan White, Desmond Groothius, Adam Kanner, Glenn Edelman, Elazer R. Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular injury in a porcine model |
| title | Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular injury in a porcine model |
| title_full | Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular injury in a porcine model |
| title_fullStr | Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular injury in a porcine model |
| title_full_unstemmed | Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular injury in a porcine model |
| title_short | Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular injury in a porcine model |
| title_sort | ultrasound guided percutaneous delivery of tissue engineered endothelial cells to the adventitia of stented arteries controls the response to vascular injury in a porcine model |
| url | http://hdl.handle.net/1721.1/102309 https://orcid.org/0000-0002-7832-7156 |
| work_keys_str_mv | AT nugenthelenm ultrasoundguidedpercutaneousdeliveryoftissueengineeredendothelialcellstotheadventitiaofstentedarteriescontrolstheresponsetovascularinjuryinaporcinemodel AT ngyinshan ultrasoundguidedpercutaneousdeliveryoftissueengineeredendothelialcellstotheadventitiaofstentedarteriescontrolstheresponsetovascularinjuryinaporcinemodel AT whitedesmond ultrasoundguidedpercutaneousdeliveryoftissueengineeredendothelialcellstotheadventitiaofstentedarteriescontrolstheresponsetovascularinjuryinaporcinemodel AT groothiusadam ultrasoundguidedpercutaneousdeliveryoftissueengineeredendothelialcellstotheadventitiaofstentedarteriescontrolstheresponsetovascularinjuryinaporcinemodel AT kannerglenn ultrasoundguidedpercutaneousdeliveryoftissueengineeredendothelialcellstotheadventitiaofstentedarteriescontrolstheresponsetovascularinjuryinaporcinemodel AT edelmanelazerr ultrasoundguidedpercutaneousdeliveryoftissueengineeredendothelialcellstotheadventitiaofstentedarteriescontrolstheresponsetovascularinjuryinaporcinemodel |