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Marrow Stromal Cells as Universal Donor Cells for Myocardial Regenerative Therapy: Their Unique Immune Tolerance  Rony Atoui, MD, MS, Juan-Francisco Asenjo,

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Presentation on theme: "Marrow Stromal Cells as Universal Donor Cells for Myocardial Regenerative Therapy: Their Unique Immune Tolerance  Rony Atoui, MD, MS, Juan-Francisco Asenjo,"— Presentation transcript:

1 Marrow Stromal Cells as Universal Donor Cells for Myocardial Regenerative Therapy: Their Unique Immune Tolerance  Rony Atoui, MD, MS, Juan-Francisco Asenjo, MD, Minh Duong, BS, Guangyong Chen, MD, Ray C.-J. Chiu, MD, PhD, Dominique Shum- Tim, MD, MS  The Annals of Thoracic Surgery  Volume 85, Issue 2, Pages (February 2008) DOI: /j.athoracsur Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 Gross heart specimen after human marrow stromal cell implantation and staining for β-galactosidase activity. Note the blue discoloration seen around the infarcted area. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 2 A represents a scar after coronary ligation, B shows a connexin-43 staining from a control myocardium (group III), and C represents a section with rat marrow stromal cell implantation (group II). Representative sections of infarcted rat myocardium stained with hematoxylin and eosin (C, D), troponin IC (E), and connexin-43 (F) with evidence of engraftment of human marrow stromal cells (arrows) harvested at 1 (D), 3 (E), and 6 weeks (F) after coronary ligation (group I). Note the absence of any significant inflammatory reaction despite the lack of immunosuppression. Scale bar represents 30 μm. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 3 Sections of infarcted myocardium stained with hematoxylin and eosin (A and C) and immunostained with antibodies against connexin-43 (B) 6 to 8 weeks after transplantation. At 6 and 8 weeks, β-galactosidase–positive cells were more elongated and aligned within the muscle fibers (black arrow) compared with the cells harvested at an earlier stage. Note the connexin-43–positive gap junctions (white arrows) between an engrafted cell (blue arrow) and host cardiomyocytes (B). Scale bar represents 15 μm. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 4 Sections taken 8 weeks after human marrow stromal cell transplantation. In situ hybridization of the Y chromosome in human marrow stromal cells stains red. Figures A and B represent sections taken from group I, whereas C and D represent positive and negative controls, respectively. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

6 Fig 5 Extensive cellular infiltration noted at 3 (A) and 8 (C) days after transplantation of human fibroblasts. Only a few surviving labeled fibroblasts were found at 8 days. Immunostaining with CD68 showing massive infiltration of macrophages (brown spots) at 5 days after injection of fibroblasts (B). This is in contrast to the minimal infiltration seen at 1 week after human marrow stromal cell transplantation (D). Arrows point to the cellular infiltration around the implanted cells. Scale bar represents 30 μm. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

7 Fig 6 Polymerase chain reaction product specific for the human Y chromosome (DYS390 sequence). On the left, a band is seen in all the female rat hearts with human male marrow stromal cells at 6 (T1, T2) and 8 weeks (T3–T5) after ligation. Human male marrow stromal cells and myocardium from untreated female rats were used as positive (P) and negative (U) controls, respectively. On the right, a positive band is seen in rat hearts after human fibroblast implantation at 3 (F1) and 5 days (F2) after ligation. A very light signal is seen at 8 days after ligation (F3). No signal is seen in the samples taken at 10 (F4) and 12 days (F5), suggesting complete rejection of the human fibroblasts. Human male skin fibroblasts and myocardium from untreated female rats were used as positive (P) and negative controls (U), respectively. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

8 Fig 7 Effects on ventricular function. At 6 to 8 weeks after marrow stromal cell implantation, ejection fraction (A) and fractional shortening (B) were significantly higher in the marrow stromal cell–transplanted groups (I and II) and continued to decline in the control group (III). No significant changes in the left ventricular end-systolic diameter (LVESD) (C) and left ventricular end-diastolic diameter (LVEDD) (D) were seen in the marrow stromal cell–transplanted groups with time, in contrast to the increase in both dimensions with time in the control group. *p < 0.05 when compared with group III at 8 weeks after ligation; †p < 0.05 when compared with results at 3 to 4 days after ligation. Data are represented as mean ± standard error of the mean. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

9 Fig 8 Representative photomicrographs of infarcted heart specimens taken 8 weeks after culture-medium injection (A) and human marrow stromal cell transplantation (B). C represents a normal rat heart. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions


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