Fig. 4

MSCs implanted in vivo in the infarcted left ventricle wall improve cardiac recovery in preclinical models and patient studies. A diagram of cellular therapy approaches tested with MSCs is shown. 1—Peripheral veinous infusion. 2—Endomyocardial delivery via injection catheter. 3—Direct myocardial injection during open chest surgery such as for coronary artery bypass grafting. 4—Delivery via intracoronary arteries. MSCs release anti-inflammatory factors and interact with endogenous cells to improve physiological outcome despite limited engraftment. Panels (a−d)¹⁴⁵—a Porcine female heart receiving male allo-MSC injection show greater repair processes with active stimulation of endogenous cardiomyocyte cell-cycle activity (phospho H3 staining) which are associated with greater functional recovery. b Following direct injection of male MSCs near the infarct border, there are increased phospho-H3 detected at 8 weeks in the infarct (IZ) and border zones (BZ) compared to the remote zones (RZ) away from the infarct. The error bars indicate the mean ± SEM. c, d Immunohistology of data in (a) and (b). Results of clinical delivery of MSCs (e) are shown with MRI cross-section of hearts from patients receiving standard of care or standard of care plus MSCs in the PROMETHEUS trial.¹⁴¹ The MSC-treated hearts showed smaller infarcts at 12 and 18 months. The MSC-treated patients also had greater heart function (ejection fraction) and stamina (6 min walk test).¹⁴¹ The error bars indicate the mean ± SEM. Figures reproduced with permission of Kluwers Wolter/Circulation Research/Hare.^141,145