Hyperbaric oxygenation enhances transplanted cell graft and functional recovery in the infarct heart.
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.
Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA. mahmood.khan@osumc.edu
Mahmood
M
Khan
Sarath
S
Meduru
Iyyapu K
IK
Mohan
M Lakshmi
ML
Kuppusamy
Sheik
S
Wisel
Aditi
A
Kulkarni
Brian K
BK
Rivera
Robert L
RL
Hamlin
Periannan
P
Kuppusamy
D000200:Action Potentials; D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D018031:Connexin 43 / Q000378:metabolism; D005290:Ferric Compounds / Q000378:metabolism; D005355:Fibrosis; D006931:Hyperbaric Oxygenation; D019012:Integrin beta1 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic; D010313:Partial Pressure; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function; D020107:Troponin T / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D016277:Ventricular Function, Left
D018031:Connexin 43; D005290:Ferric Compounds; D019012:Integrin beta1; D020107:Troponin T; D042461:Vascular Endothelial Growth Factor A; C000499:ferric oxide