Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes
The neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulm...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-09-01
|
| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2021.715717/full |
| _version_ | 1819239904541933568 |
|---|---|
| author | Valeria Vincenza Alvino Anita C. Thomas Mohamed T. Ghorbel Filippo Rapetto Srinivas A. Narayan Michael Kilcooley Dominga Iacobazzi Michele Carrabba Marco Fagnano William Cathery Elisa Avolio Massimo Caputo Paolo Madeddu |
| author_facet | Valeria Vincenza Alvino Anita C. Thomas Mohamed T. Ghorbel Filippo Rapetto Srinivas A. Narayan Michael Kilcooley Dominga Iacobazzi Michele Carrabba Marco Fagnano William Cathery Elisa Avolio Massimo Caputo Paolo Madeddu |
| author_sort | Valeria Vincenza Alvino |
| collection | DOAJ |
| description | The neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulmonary artery (PA) reconstruction. Within each of five trios formed by 4-week-old female littermate piglets, one element (the donor) was sacrificed to provide a source of CPs, while the other two elements (the graft recipients) were allowed to reach the age of 10 weeks. During this time interval, culture-expanded donor CPs were seeded onto swine small intestinal submucosa (SIS) grafts, which were then shaped into conduits and conditioned in a flow bioreactor. Control unseeded SIS conduits were subjected to the same procedure. Then, recipient piglets were randomized to surgical reconstruction of the left PA (LPA) with unseeded or CP-seeded SIS conduits. Doppler echocardiography and cardiac magnetic resonance imaging (CMRI) were performed at baseline and 4-months post-implantation. Vascular explants were examined using histology and immunohistochemistry. All animals completed the scheduled follow-up. No group difference was observed in baseline imaging data. The final Doppler assessment showed that the LPA’s blood flow velocity was similar in the treatment groups. CMRI revealed a mismatch in the average growth of the grafted LPA and contralateral branch in both treatment groups. Histology of explanted arteries demonstrated that the CP-seeded grafts had a thicker luminal cell layer, more intraparietal arterioles, and a higher expression of endothelial nitric oxide synthase (eNOS) compared with unseeded grafts. Moreover, the LPA stump adjacent to the seeded graft contained more elastin and less collagen than the unseeded control. Syngeneic CP engineering did not accomplish the primary goal of supporting the graft’s growth but was able to improve secondary outcomes, such as the luminal cellularization and intraparietal vascularization of the graft, and elastic remodeling of the recipient artery. The beneficial properties of neonatal CPs may be considered in future bioengineering applications aiming to reproduce the cellular composition of native arteries. |
| first_indexed | 2024-12-23T13:59:32Z |
| format | Article |
| id | doaj.art-2389eec8c4f148f888db784ea00ac5a8 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-23T13:59:32Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-2389eec8c4f148f888db784ea00ac5a82022-12-21T17:44:21ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852021-09-01910.3389/fbioe.2021.715717715717Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac PericytesValeria Vincenza AlvinoAnita C. ThomasMohamed T. GhorbelFilippo RapettoSrinivas A. NarayanMichael KilcooleyDominga IacobazziMichele CarrabbaMarco FagnanoWilliam CatheryElisa AvolioMassimo CaputoPaolo MadedduThe neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulmonary artery (PA) reconstruction. Within each of five trios formed by 4-week-old female littermate piglets, one element (the donor) was sacrificed to provide a source of CPs, while the other two elements (the graft recipients) were allowed to reach the age of 10 weeks. During this time interval, culture-expanded donor CPs were seeded onto swine small intestinal submucosa (SIS) grafts, which were then shaped into conduits and conditioned in a flow bioreactor. Control unseeded SIS conduits were subjected to the same procedure. Then, recipient piglets were randomized to surgical reconstruction of the left PA (LPA) with unseeded or CP-seeded SIS conduits. Doppler echocardiography and cardiac magnetic resonance imaging (CMRI) were performed at baseline and 4-months post-implantation. Vascular explants were examined using histology and immunohistochemistry. All animals completed the scheduled follow-up. No group difference was observed in baseline imaging data. The final Doppler assessment showed that the LPA’s blood flow velocity was similar in the treatment groups. CMRI revealed a mismatch in the average growth of the grafted LPA and contralateral branch in both treatment groups. Histology of explanted arteries demonstrated that the CP-seeded grafts had a thicker luminal cell layer, more intraparietal arterioles, and a higher expression of endothelial nitric oxide synthase (eNOS) compared with unseeded grafts. Moreover, the LPA stump adjacent to the seeded graft contained more elastin and less collagen than the unseeded control. Syngeneic CP engineering did not accomplish the primary goal of supporting the graft’s growth but was able to improve secondary outcomes, such as the luminal cellularization and intraparietal vascularization of the graft, and elastic remodeling of the recipient artery. The beneficial properties of neonatal CPs may be considered in future bioengineering applications aiming to reproduce the cellular composition of native arteries.https://www.frontiersin.org/articles/10.3389/fbioe.2021.715717/fullpericytesgraftscongenital heart diseasepulmonary arterytissue engineering |
| spellingShingle | Valeria Vincenza Alvino Anita C. Thomas Mohamed T. Ghorbel Filippo Rapetto Srinivas A. Narayan Michael Kilcooley Dominga Iacobazzi Michele Carrabba Marco Fagnano William Cathery Elisa Avolio Massimo Caputo Paolo Madeddu Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes Frontiers in Bioengineering and Biotechnology pericytes grafts congenital heart disease pulmonary artery tissue engineering |
| title | Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes |
| title_full | Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes |
| title_fullStr | Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes |
| title_full_unstemmed | Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes |
| title_short | Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes |
| title_sort | reconstruction of the swine pulmonary artery using a graft engineered with syngeneic cardiac pericytes |
| topic | pericytes grafts congenital heart disease pulmonary artery tissue engineering |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2021.715717/full |
| work_keys_str_mv | AT valeriavincenzaalvino reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes AT anitacthomas reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes AT mohamedtghorbel reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes AT filipporapetto reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes AT srinivasanarayan reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes AT michaelkilcooley reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes AT domingaiacobazzi reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes AT michelecarrabba reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes AT marcofagnano reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes AT williamcathery reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes AT elisaavolio reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes AT massimocaputo reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes AT paolomadeddu reconstructionoftheswinepulmonaryarteryusingagraftengineeredwithsyngeneiccardiacpericytes |