Survival of human marrow stem cells (MSCs) implanted into acutely infarcted rat myocardium: A xenotransplant model

S22

Cardiothoracic Surgery

J Am Coll Surg

Table. Transmural stress Aneurysm Circumferential Stress Endocardium Midwall Epicardium

IDM

FDM

Endocardium Midwall Epicardium

IDM

FDM

Remote IDM

FDM

29.7⫾4.5 39.9⫾7.4 26.2⫾1.1 37.8⫾4.5 18.9⫾1 30.3⫾2 31.4⫾3.7 33.1⫾5.4 22.5⫾1.6 31.4⫾2.6 14.6⫾1.2 24.5⫾2 31.3⫾3 30.8⫾3.7 20.2⫾1.7 35.2⫾2.5 13.9⫾1.4 22.7⫾2.5 Aneurysm

Longitudinal Stress

Border-zone

IDM

FDM

Border-zone IDM

FDM

Remote IDM

FDM

28.5⫾2.3 40.3⫾9.9 13.5⫾1.5 3.4⫾2 5.57⫾0.5 ⫺5.5⫾1 29.2⫾1.7 33.4⫾6.7 12.7⫾1.4 4.3⫾1 5.0⫾0.7 ⫺2.2⫾0.9 28.5⫾1.8 31.6⫾4.4 12.0⫾2.1 5.9⫾0.1 8.45⫾0.9 1.1⫾0.7

CONCLUSIONS: IDM failed to demonstrate transmural stress variation when compared to the gold standard FDM. Therefore, FDM should be the method of choice to predict stress in patients with LVA.

Murine carotid aneurysms develop without down regulation of Nogo-B expression: A novel model for human thoracic aneurysms Stephen P Maloney MD, Alexander Yakimov MD, Akihito Muto MD, PhD, Paul Tang MD, Jose Pimiento MD, Fabio Kudo MD, PhD, Tormod Westvik MD, Stanley Dudrick MD, William Sessa PhD, George Tellides MD, PhD, Alan Dardik MD, PhD Yale University School of Medicine, Waterbury, CT INTRODUCTION: Although abdominal aortic aneurysms are associated with smooth muscle cell (SMC) apoptosis, ascending thoracic aneurysms are associated with preserved SMC density. Decreased expression of Nogo-B has recently been described as a marker of vascular injury. To determine whether proximal thoracic aneurysms are associated with injury, we examined the expression of Nogo-B in human specimens and a mouse model. METHODS: Normal and aneurysmal human ascending thoracic aortic surgical specimens (n⫽24) were analyzed for Nogo-B mRNA expression using quantitative PCR. Aneurysms were induced in adult (3 mo) C57Bl/6 mice by periadventitial application of CaCl2 (0.5M) to the right carotid artery. Vessel diameter was measured using a calibrated grid and compared to the contralateral carotid artery; aneurysmal and control specimens were analyzed for Nogo-B using qPCR. RESULTS: Human aortic aneurysms had preserved SMC density and Nogo-B expression compared to nonaneurysmal aortae (aneurysms, 0.256 ⫾ 0.08 vs. control, 0.152 ⫾ 0.02; p⫽0.2). Murine carotid aneurysms were 26% larger at 5 weeks (525 ⫾ 8 `ım, vs. 389 ⫾ 11 `ım; n⫽7; p⬍.0001, ANOVA). Murine aneurysms had increased expression of both Nogo-AB (14 ⫾ 1 vs. 9 ⫾ 3; p⫽0.003) and Nogo-B (46 ⫾ 18 vs. 18 ⫾ 4; p⫽0.02) compared to control arteries. CONCLUSIONS: Preserved Nogo-B expression in human thoracic aneurysms suggests that proximal aortic aneurysms develop without vessel injury. Murine carotid aneurysms similarly have increased

Nogo-B expression, also suggesting aneurysmal formation without injury. Murine carotid aneurysms may be a novel model for human thoracic aneurysm development.

Survival of human marrow stem cells (MSCs) implanted into acutely infarcted rat myocardium: A xenotransplant model Rony Atoui MD, Juan Francisco Asenjo MD, Minh Duong BSc, Ray Chiu MD, PhD, Dominique Shum-Tim MD McGill University Health Center, Montreal, QC, Canada INTRODUCTION: Cellular transplantation is a promising approach for myocardial regeneration therapy. Recently we have demonstrated the unique immune tolerance of MSCs obtained from mice and pigs. In order to confirm these findings in human cells, which currently remain controversial, purified clonal human MSCs characterized with specific CD markers, were used as donor cells in a xenogeneic transplant model. METHODS: Myocardial infarctions were created in Lewis rats by proximal left coronary ligation. The animals were randomized into 3 groups. In group I (n⫽20), lac-Z labeled human MSC (3⫻106 cells) were implanted around the infarcted area. In group II (n⫽10), isogenic rat MSC were used instead and in group III (n⫽10), culture medium was used. No immunosuppression was given at any time. Immunohistochemical staining was done on specimens taken serially to assess for the presence of ␤-galactosidase activity in the recipient hearts. RESULTS: In group I and II, engrafted MSC were detected within the rat myocardium beyond at least 4 weeks after cell transplantation without immunosuppression. No extensive cellular infiltrates were noted. Furthermore, some of these cells started to differentiate into a mature cardiomyocytic phenotype. CONCLUSIONS: Human MSC implanted into immunologically mismatched ischemic myocardium were tolerated, with persistent engraftment of these cells. This study confirms the unique immune tolerance of human MSCs, indicating the feasibility of using these cells as “universal donor cells” with fascinating economic and clinical implications whereby xenogeneic or allogeneic MSC could be expanded, cryopreserved and available on the shelf, ready for implantation into patients following myocardial infarction.

Cardiopulmonary bypass with cardioplegic arrest activates protein kinase C in the human myocardium Neel R Sodha MD, Richard Clements PhD, Jun Feng MD, PhD, Munir Boodhwani MD, Basel Ramlawi MD, Shigetoshi Mieno MD, PhD, Cesario Bianchi MD, PhD, Frank W Sellke MD Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA INTRODUCTION: The Protein Kinase C family consists of 12 isoforms, of which six have been found in human myocardium (alpha,