Bone marrow–derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction.

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Bone marrow–derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site Jussi Mäkelä, BM, Kari Ylitalo, MD, PhD, Siri Lehtonen, PhD, Sebastian Dahlbacka, MD, Eija Niemelä, BM, Kai Kiviluoma, MD, PhD, Jussi Rimpiläinen, MD, PhD, Hanna Alaoja, BM, Timo Paavonen, MD, PhD, Petri Lehenkari, MD, PhD, Tatu Juvonen, MD, PhD, Vesa Anttila, MD, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 134, Issue 3, Pages 565-573 (September 2007) DOI: 10.1016/j.jtcvs.2007.05.004 Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Bone marrow–derived mononuclear cell (BMMC) injection at the infarction site enables ejection fraction recovery. The ejection fraction decreased after infarction critically (>15%) in both groups (!P = .03). After the 3-week recovery period, the ejection fraction increased significantly in the BMMC group (*P = .02) but remained at the same decreased level in the control group. Data points represent actual median values ± standard deviation. The Journal of Thoracic and Cardiovascular Surgery 2007 134, 565-573DOI: (10.1016/j.jtcvs.2007.05.004) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Injected DiI-labeled cells remain at the infarct site. Transplanted DiI-labeled (white arrows) cells were detected by using a fluorescent microscope (magnification ×20) from the infarcted area (A) and from some of the perihilar lymph nodes (B). A sample from undamaged heart muscle was negative (C), as were samples from the liver (D), spleen (E), and lungs (F). Bars = 100 μm. The Journal of Thoracic and Cardiovascular Surgery 2007 134, 565-573DOI: (10.1016/j.jtcvs.2007.05.004) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Injected DiI-labeled cells differentiate at the injection site. DiI-positive cells in the granulation tissue area at the infarcted myocardium showed positive expression of α-smooth muscle actin (α-SMA; A and B), Ki-67 (C and D; magnification ×20), vimentin (E and F; magnification ×40), and muscle-specific actin (MSA; G and H; magnification ×60). Bars = 20 μm. The Journal of Thoracic and Cardiovascular Surgery 2007 134, 565-573DOI: (10.1016/j.jtcvs.2007.05.004) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Injection of bone marrow–derived mononuclear cells (BMMC) enhances cell survival and recruitment at the infarction site parenchyma. Larger quantities of living cells in the necrotic area were observed with a fluorescent microscope (magnification ×20) in the BMMC group by using Hoechst staining (A and B) compared with the control group (E and F). In cell counting a significant difference between the groups could readily be observed (I; ***P < .001). Similarly, a larger number of Stro-1–positive cells was detected in the BMMC group (C, D, and J; P < .001) compared with the control group (G and H). The highest density of Stro-1–positive cells was detected at the vessel walls in the BMMC group (D) in contrast to the control group (H). Bars in A, C, E, and G = 100 μm; bars in B, D, F, and H = 20 μm. The Journal of Thoracic and Cardiovascular Surgery 2007 134, 565-573DOI: (10.1016/j.jtcvs.2007.05.004) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Injection of bone marrow–derived mononuclear cells (BMMC) promotes postinfarction remodeling. Analysis of the immunohistologic staining with a light microscope revealed differences between the control and BMMC groups (images with ×10 magnification are shown). Enhanced vimentin staining (A and C), indicating a larger quantity of mesenchymal cells in the necrotic area (E; P < .01) and in the border zone (F; P < .001), could be seen in the BMMC group. For the muscle actin staining (B and D), the proportional area of cell coverage was greater in the granulation tissue area (G) in the BMMC group (P = .035). Bars = 50 μm. The Journal of Thoracic and Cardiovascular Surgery 2007 134, 565-573DOI: (10.1016/j.jtcvs.2007.05.004) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions