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Hypoxia-preconditioned mesenchymal stromal cells improve cardiac function in a swine model of chronic myocardial ischaemia.
MedLine Citation:
PMID:  23100292     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVES: Cell loss during cardiac injection and hostility of the host-tissue microenvironment have the potential to diminish the overall effect of stem cell therapy. The purposes of this study were to evaluate the effect of a hypoxic preconditioning of mesenchymal stromal cells (MSC), to determine its safety and effectiveness, and to improve the efficacy of cell therapy using MSC in the setting of chronic myocardial ischaemia in swine. METHODS: Myocardial ischaemia was induced by an ameroid constrictor. Human MSC were cultured under normoxic (20% O(2)) or hypoxic conditions (1.5% O(2)) before transplantation. One month after ischaemia, pigs were randomly assigned to saline injection (sham), and 1 10(6)/kg normoxic or hypoxic MSC transplantation into the ischaemic inferior-lateral zone. RESULTS: Twenty-seven pigs were operated on and the mortality rate was 33.3%. The remaining 18 animals were randomly assigned to sham (n = 4), normoxic (n = 8) or hypoxic MSC (n = 6) treatment. Global systolic (left ventricle ejection fraction, P = 0.04) and diastolic (E/E(a), P = 0.008) functions were increased in the hypoxic group compared with other groups. The peak of 2-dimensional longitudinal strain was less altered in the hypoxic group compared with other groups (P < 0.001). Haemodynamic data showed that dP/dT max was improved in the hypoxic group compared with the other group (P < 0.01). Capillary density was increased in the hypoxic group (P = 0.001). MSC density was significantly higher in the ischaemic zone in the hypoxic group (P < 0.01). CONCLUSION: MSC engraftment with hypoxic preconditioning significantly improves capillary density and cell survival, resulting in improvement in global, regional and diastolic left ventricular functions. This highlights the therapeutic potential of transplanting hypoxic-preconditioned MSC in the setting of chronic ischaemic heart failure.
Authors:
Jeremie Jaussaud; Matthieu Biais; Joachim Calderon; Jean Chevaleyre; Pascale Duchez; Zoran Ivanovic; Thierry Couffinhal; Laurent Barandon
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-25
Journal Detail:
Title:  European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery     Volume:  -     ISSN:  1873-734X     ISO Abbreviation:  Eur J Cardiothorac Surg     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804069     Medline TA:  Eur J Cardiothorac Surg     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Adaptation cardiovasculaire à líschémie, INSERM, Pessac, France.
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