(A) Bioluminescent images in a representative live animal injected with mISL1-CPC spheroids and recorded at 3 different time points: left (72 hours); middle (2 weeks); right (4 weeks). The far right: Graph representing the bioluminescence signal quantified in live animals injected with mISL1-CPC spheroids, n = 7. Statistical analysis performed with 1-way repeated measurements ANOVA with Greenhouse-Geisser correction (P = 0.35). (B) Bioluminescent image of a heart explanted 4 weeks after artery ligation and injection with mISL1-CPC spheroids. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. In A and B, the numbers in the scale bars were introduced manually to enlarge the font size. (C and D) Histological sections of explanted hearts 4 weeks after surgery, showing that mISL1-CPC spheroids differentiated into cardiomyocytes (C) and endothelial cells (D). Note the integration of donor endothelial cells in host blood vessels. Pictures in C represent ×10 (left), ×20 (second and third from left), and ×60 (fourth and fifth from left) magnification. Pictures in D represent ×10 (left), ×20 (second from left), and ×60 (third and fourth from left) magnification. White rectangles in ×10 and ×20 pictures represent the area magnified in ×20 and ×60, respectively. Y-chromosome FISH staining (red), cTnT (green), and CD31 (cyan). White arrowheads indicate the location in the ×60 pictures of Y-FISH⁺/cTnT⁺ and Y-FISH⁺/CD31⁺ cells in C and D, respectively. Scale bars: 100 μm in ×10, 50 μm in ×20, and 20 μm in ×60 pictures. (E) Quantification of double-positive Y-FISH/cTnT, Y-FISH/CD31, and Y-FISH/SMA cells in 4 infarcted hearts 4 weeks after surgery/cell injection. Seven slides, containing coronal sections, were analyzed per heart in the anatomical region where the bioluminescence was detected. See also Supplemental Figures 3 and 4.