1: J Mol
Cell Cardiol. 2009 Apr 17. [Epub ahead of print]
Hyperbaric oxygenation enhances
transplanted cell graft and functional recovery in the infarct heart.
Khan M, Meduru S, Mohan IK, Kuppusamy ML, Wisel S, Kulkarni A, Rivera BK, Hamlin RL, Kuppusamy P.
Davis Heart and
Lung Research Institute, Division of Cardiovascular Medicine, Department of
Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
A major limitation to the
application of stem-cell therapy to repair ischemic heart damage is the low
survival of transplanted cells in the heart, possibly due to poor oxygenation.
We hypothesized that hyperbaric oxygenation (HBO) can be used as an adjuvant
treatment to augment stem-cell therapy. Therefore, the goal of this study was
to evaluate the effect of HBO on the engraftment of rat bone marrow-derived
mesenchymal stem cells (MSCs) transplanted in infarct rat hearts. Myocardial
infarction (MI) was induced in Fisher-344 rats by permanently ligating the
left-anterior-descending coronary artery. MSCs, labeled with fluorescent
superparamagnetic iron oxide (SPIO) particles, were transplanted in the infarct
and peri-infarct regions of the MI hearts. HBO (100% oxygen at 2 ATA for 90
min) was administered daily for 2 weeks. Four MI groups were used: untreated
(MI); HBO; MSC; MSC+HBO. Echocardiography, electro-vectorcardiography, and
magnetic resonance imaging were used for functional evaluations. The
engraftment of transplanted MSCs in the heart was confirmed by SPIO
fluorescence and Prussian-blue staining. Immunohistochemical staining was used
to identify key cellular and molecular markers including CD29, troponin-T,
connexin-43, VEGF, alpha-smooth-muscle actin, and von Willebrand factor in the
tissue. Compared to MI and MSC groups, the MSC+HBO group showed a significantly
increased recovery of cardiac function including left-ventricular (LV) ejection
fraction, fraction shortening, LV wall thickness, and QRS vector. Further, HBO
treatment significantly increased the engraftment of CD29-positive cells,
expression of connexin-43, troponin-T and VEGF, and angiogenesis in the infarct
tissue. Thus, HBO appears to be a potential and clinically-viable adjuvant
treatment for myocardial stem-cell therapy.
PMID: 19376124 [PubMed - as supplied by publisher]
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