Significant improvement of heart function by cotransplantation of human mesenchymal stem cells and fetal cardiomyocytes in postinfarcted pigs Jiang-Yong.

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Significant improvement of heart function by cotransplantation of human mesenchymal stem cells and fetal cardiomyocytes in postinfarcted pigs Jiang-Yong Min, MD, Matthew F Sullivan, BS, Yinke Yang, MD, PhD, Jian-Ping Zhang, MD, Kimber L Converso, BS, James P Morgan, MD, PhD, Yong-F.u Xiao, MD, PhD The Annals of Thoracic Surgery Volume 74, Issue 5, Pages 1568-1575 (November 2002) DOI: 10.1016/S0003-4975(02)03952-8

Fig 1 Hemodynamic measurements in postinfarcted porcine hearts before ligation (Baseline), and 1 hour and 6 weeks after myocardial infarction (MI). Cell transplantation of hMSCs alone or hMSCs plus hFCs improved the ventricular function compared with the MI control animals. There is a trend of greater beneficial effects on ventricular function with cotransplantation of hMSCs plus hFCs compared with transplantation of hMSCs alone. MI-Control = postinfarcted pigs with transplantation of the cell-free medium (n = 7); MI-hMSCs = postinfarcted pigs with transplantation of hMSCs alone (n = 6); MI-hMSCs+hFCs = postinfarcted pigs with cotransplantation of hMSCs plus hFCs (n = 7). (a) LVSP = the left ventricular systolic pressure; (b) LVEDP = the left end-diastolic pressure; (c) +dP/dt = the peak rate of pressure rise; (d) −dP/dt = the peak rate of pressure fall. *p < 0.05, **p < 0.01 versus MI-Control at 6 weeks after MI; #p < 0.05 versus MI-hMSCs 6 weeks after MI. (hFCs = human fetal cardiomyocytes; hMSCs = human mesenchymal stem cells.) The Annals of Thoracic Surgery 2002 74, 1568-1575DOI: (10.1016/S0003-4975(02)03952-8)

Fig 2 Morphology of hematoxylin & eosin (H&E) staining of normal porcine myocardium (a), and infarcted myocardium with medium injection (b and c). Green fluorescent protein–positive clusters sectioned from myocardial infarction pig hearts with transplantation of hMSCs alone and cotransplantation of hMSCs plus hFCs are shown in d and g, respectively. The H&E staining of infarcted porcine myocardium showed cell grafts within the infarcted zone with transplantation of hMSCs alone (e and f) and cotransplantation of hMSCs plus hFCs (h and i). The arrows in b, e, and h point to the areas corresponding with the magnification in c, f, and i. (hFCs = human fetal cardiomyocytes; hMSCs = human mesenchymal stem cells.) The Annals of Thoracic Surgery 2002 74, 1568-1575DOI: (10.1016/S0003-4975(02)03952-8)

Fig 3 Positive immunofluorescent staining to α-MHC and cTnI were found in normal (a and b, respectively) and postinfarcted myocardium within the infarcted zone transplanted with hMSCs alone (e and f) and cotransplantation with hMSCs plus hFCs (g and h, respectively), but not in injured porcine myocardium with medium injection (c and d, respectively). The results were obtained from different animals for fluorescent labeling of α-MHC and cTnI (×200). (α-MHC = α-myosin heavy chain; cTnI = cardiac troponin I; hFCs = human fetal cardiomyocytes; hMSCs = human mesenchymal stem cells.) The Annals of Thoracic Surgery 2002 74, 1568-1575DOI: (10.1016/S0003-4975(02)03952-8)

Fig 4 Double staining for GFP and cTnI of injured myocardium cotransplanted with hMSCs plus hFCs. a and b show the staining of GFP by a monoclonal anti-GFP antibody and of cTnI by a polyclonal anti-cTnI antibody, respectively. The merger (c) of GFP and cTnI staining demonstrates that engrafted GFP-positive cells differentiated into cardiac myocytes (×200). (CTnI = cardiac troponin I; GFP = green fluorescent protein; hFCs = human fetal cardiomyocytes; hMSCs = human mesenchymal stem cells.) The Annals of Thoracic Surgery 2002 74, 1568-1575DOI: (10.1016/S0003-4975(02)03952-8)

Fig 5 Blood flow measurements with the neutron microsphere technique in postinfarcted porcine hearts at resting condition (a) and with pacing stress (b). MI-Control = postinfarcted pigs with transplantation of the cell-free medium (n = 7); MI-hMSCs = postinfarcted pigs with transplantation of MI-hMSCs (n = 6); MI-hMSCs+hFCs = postinfarcted pigs with cotransplantation of hMSCs plus hFCs (n = 7). *p < 0.05; **p < 0.01 versus MI-Control; #p < 0.05 versus MI-hMSCs. (hFCs = human fetal cardiomyocytes; hMSCs = human mesenchymal stem cells.) The Annals of Thoracic Surgery 2002 74, 1568-1575DOI: (10.1016/S0003-4975(02)03952-8)