Functional impact of targeted closed-chest transplantation of bone marrow cells in rats with acute myocardial ischemia/reperfusion injury.
Intramyocardial transplantation of bone marrow-derived stem cells is a potential therapeutic option after myocardial infarction (MI). Intramyocardial administration is invasive but allows efficient and targeted stem cell delivery. Aims of this study were validation of minimal-invasive, echo-guided closed-chest cell transplantation (CTx) of mononuclear (MNC) or mesenchymal stem cells (MSC) and quantification of systolic left ventricular function and assessment of contractile reserve with high-resolution reconstructive 3D-echocardiography (r3D-echo) 3 weeks after CTx. Female Fischer344 rats received syngeneic male MNC, MSC, or medium after myocardial ischemia and reperfusion via echo-guided percutaneous injection (open-chest for control). Left ventricular systolic function was measured and dysfunctional myocardium was quantified with r3D-echo. For investigation of contractile reserve and myocardial viability r3D-echo was additionally conducted during low-dose dobutamine 3 weeks after CTx. Cell persistence after echo-guided CTx was quantified via real-time PCR; scar size was measured histologically. Echo-guided percutaneous CTx was feasible in all animals (n = 30) without periprocedural complications. After 3 weeks, 1.4 +/- 1.1% of transplanted MNC and 1.9 +/- 1.2% of MSC were detected. These numbers were comparable to those after open-chest intramyocardial injection of MNC (0.8 +/- 1.1%; n = 8, p = 0.3). In r3D-echo no functional benefit was associated with CTx after MI and reperfusion. All groups (MNC, MSC, and controls) revealed a significant decrease of dysfunctional myocardium and similar contractile reserve during inotropic stimulation.In conclusion, percutaneous echo-guided closed-chest CTx promises to be an effective and safe approach for CTx in small-animal research. However, intramyocardial CTx of MNC or MSC had no influence on systolic function and contractile reserve after reperfused MI.
Ghanem
Alexander
A
Department of Medicine/Cardiology, University of Bonn, Bonn, Germany.
Ziomka
Agnieszka
A
Krausgrill
Benjamin
B
Schenk
Kerstin
K
Troatz
Clemens
C
Miszalski-Jamka
Tomas
T
Nickenig
Georg
G
Tiemann
Klaus
K
Müller-Ehmsen
Jochen
J
D000208:Acute Disease; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D019560:Echocardiography, Three-Dimensional; D005260:Female; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D019060:Minimally Invasive Surgical Procedures; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011916:Rats, Inbred F344; D016277:Ventricular Function, Left / Q000502:physiology