Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction

被引：42

作者：

Alvino, Valeria Vincenza ^{[1
]}

Fernandez-Jimenez, Rodrigo ^{[3
,4
]}

Rodriguez-Arabaolaza, Iker ^{[1
]}

Slater, Sadie ^{[1
]}

Mangialardi, Giuseppe ^{[1
]}

Avolio, Elisa ^{[1
]}

Spencer, Helen ^{[1
]}

Culliford, Lucy ^{[1
]}

Hassan, Sakinah ^{[1
]}

Sueiro Ballesteros, Lorena ^{[2
]}

Herman, Andrew ^{[2
]}

Ayaon-Albarran, Ali ^{[3
,5
]}

Galan-Arriola, Carlos ^{[3
]}

Sanchez-Gonzalez, Javier ^{[6
]}

Hennessey, Helena ^{[7
]}

Delmege, Catherine ^{[7
]}

Ascione, Raimondo ^{[1
]}

Emanueli, Costanza ^{[1
]}

Angelini, Gianni Davide ^{[1
]}

Ibanez, Borja ^{[3
,8
,9
]}

Madeddu, Paolo ^{[1
]}

机构：

[1] Univ Bristol, Sch Clin Sci, Bristol Heart Inst, Upper Maudlin Rd, Bristol BS2 8HW, Avon, England

[2] Univ Bristol, Sch Cellular & Mol Med, Bristol, Avon, England

[3] Ctr Nacl Invest Cardiovasc Carlos III CNIC, Madrid, Spain

[4] Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA

[5] La Paz Univ Hosp, Adult Cardiac Surg Dept, Madrid, Spain

[6] Philips Healthcare, Madrid, Spain

[7] Southmead Hosp, Bristol Genet Lab, Bristol, Avon, England

[8] IIS Fdn Jimenez Diaz Hosp, Madrid, Spain

[9] Ctr Invest Biomed Red Cardiovasc CIBERCV, Madrid, Spain

来源：

JOURNAL OF THE AMERICAN HEART ASSOCIATION | 2018年 / 7卷 / 02期

基金：

英国医学研究理事会;

关键词：

angiogenesis; cell therapy; large animal models; myocardial infarction; pericytes; MESENCHYMAL STEM-CELLS; PROGENITOR CELLS; ISCHEMIC-HEART; CARDIOMYOCYTE PROLIFERATION; THERAPY; MOUSE; OPTIMIZATION; METAANALYSIS; ACTIVATION; DELIVERY;

D O I：

10.1161/JAHA.117.006727

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-Transplantation of adventitial pericytes (APCs) promotes cardiac repair in murine models of myocardial infarction. The aim of present study was to confirm the benefit of APC therapy in a large animal model. Methods and Results-We performed a blind, randomized, placebo-controlled APC therapy trial in a swine model of reperfused myocardial infarction. A first study used human APCs (hAPCs) from patients undergoing coronary artery bypass graft surgery. A second study used allogeneic swine APCs (sAPCs). Primary end points were (1) ejection fraction as assessed by cardiac magnetic resonance imaging and (2) myocardial vascularization and fibrosis as determined by immunohistochemistry. Transplantation of hAPCs reduced fibrosis but failed to improve the other efficacy end points. Incompatibility of the xenogeneic model was suggested by the occurrence of a cytotoxic response following invitro challenge of hAPCs with swine spleen lymphocytes and the failure to retrieve hAPCs in transplanted hearts. We next considered sAPCs as an alternative. Flow cytometry, immunocytochemistry, and functional/cytotoxic assays indicate that sAPCs are a surrogate of hAPCs. Transplantation of allogeneic sAPCs benefited capillary density and fibrosis but did not improve cardiac magnetic resonance imaging indices of contractility. Transplanted cells were detected in the border zone. Conclusions-Immunologic barriers limit the applicability of a xenogeneic swine model to assess hAPC efficacy. On the other hand, we newly show that transplantation of allogeneic sAPCs is feasible, safe, and immunologically acceptable. The approach induces proangiogenic and antifibrotic benefits, though these effects were not enough to result in functional improvements.

引用

页数：42

共 48 条

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