Cardiac Progenitor Cells Enhance Neonatal Right Ventricular Function After Pulmonary Artery Banding

Brody Wehman, Nicholas Pietris, Grace Bigham, Osama Siddiqui, Rachana Mishra, Tieluo Li, Emily Aiello, Godly Jack, Wendy Wang, Sarah Murthi, Sudhish Sharma, Sunjay Kaushal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background C-kit+ cardiac progenitor cells (CPCs) have been shown to be safe and effective in large-animal models and in an early-phase clinical trial for adult patients with ischemic heart disease. However, CPCs have not yet been evaluated in a preclinical model of right ventricular (RV) dysfunction, which is a salient feature of many forms of congenital heart disease. Methods Human c-kit+ CPCs were generated from right atrial appendage biopsy specimens obtained during routine congenital cardiac operations. Immunosuppressed Yorkshire swine (6 to 9 kg) underwent pulmonary artery banding to induce RV dysfunction. Thirty minutes after banding, pigs received intramyocardial injection into the RV free wall with c-kit+ CPCs (1 million cells, n = 5) or control (phosphate-buffered saline, n = 5). Pigs were euthanized at 30 days postbanding. Results Banding was calibrated to a consistent rise in the RV-to-systemic pressure ratio across both groups (postbanding: CPCs = 0.76 ± 0.06, control = 0.75 ± 0.03). At 30 days postbanding, the CPCs group demonstrated less RV dilatation and a significantly greater RV fractional area of change than the control group (p = 0.002). In addition, measures of RV myocardial strain, including global longitudinal strain and strain rate, were significantly greater in the CPCs group at 4 weeks relative to control (p = 0.004 and p = 0.01, respectively). The RV free wall in the CPCs group demonstrated increased arteriole formation (p < 0.0001) and less myocardial fibrosis compared with the control group (p = 0.02). Conclusions Intramyocardial injection of c-kit+ CPCs results in enhanced RV performance relative to control at 30 days postbanding in neonatal pigs. This model is important for further evaluation of c-kit+ CPCs, including long-term efficacy.

Original languageEnglish (US)
Pages (from-to)2045-2053
Number of pages9
JournalAnnals of Thoracic Surgery
Volume104
Issue number6
DOIs
StatePublished - Dec 2017

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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