Objectives To conduct a direct head-to-head comparison of different stem cell types in vitro for various assays of potency, and in vivo for functional myocardial repair in the same mouse model of myocardial infarction. Background Adult stem cells of diverse origins (e.g., bone marrow, fat, heart) and antigenic identity have been studied for repair of the damaged heart, but the relative utility of the various cell types remains unclear. Methods Human cardiosphere-derived stem cells (CDCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose tissue-derived mesenchymal stem cells (AD-MSCs), and bone marrow mononuclear cells (BM-MNCs) were compared. Results CDCs revealed a distinctive phenotype with uniform expression of CD105, partial expression of c-kit and CD90, and negligible expression of hematopoietic markers. In vitro, CDCs showed the greatest myogenic differentiation potency, highest angiogenic potential, and relatively high production of various angiogenic and anti-apoptotic secreted factors. In vivo, injection of CDCs into the infarcted mouse hearts resulted in superior improvement of cardiac function, the highest cell engraftment and myogenic differentiation rates, and the least-abnormal heart morphology 3 weeks after treatment. CDC-treated hearts also exhibited the lowest number of apoptotic cells. The c-kit+ subpopulation purified from CDCs produced lower levels of paracrine factors and inferior functional benefit when compared to unsorted CDCs. To validate the comparison of cells from various human donors, selected results were confirmed in cells of different types derived from individual rats. Conclusions CDCs exhibit a balanced profile of paracrine factor production, and, among various comparator cell types/subpopulations, provide the greatest functional benefit in experimental myocardial infarction.

Cardiac stem cells are promising candidates for use in myocardial regenerative therapy. We test the hypothesis that growing cardiac-derived cells as three-dimensional cardiospheres may recapitulate a stem cell niche-like microenvironment, favoring cell survival and enhancing functional benefit after transplantation into the injured heart. Cardiac stem cells and supporting cells from human endomyocardial biopsies were grown as cardiospheres and compared to cells cultured under traditional monolayer condition or dissociated from cardiospheres. Cardiospheres self-assembled into stem cell niche-like structures in vitro in suspension culture, while exhibiting greater proportions of c-kit+ cells and up-regulated expression of SOX2 and Nanog. Pathway-focused PCR array, quantitative RT-PCR, and immunostaining revealed enhanced expression of stem cell-relevant factors and adhesion/extracellular-matrix molecules (ECM) in cardiospheres, including IGF-1, HDAC2, Tert, integrin-α2, laminin-β1 and MMPs. Implantation of cardiospheres in SCID mouse hearts with acute infarction disproportionately improved cell engraftment and myocardial function, relative to monolayer-cultured cells. Dissociation of cardiospheres into single cells decreased the expression of ECM and adhesion molecules and undermined resistance to oxidative stress, negating the improved cell engraftment and functional benefit in vivo. Growth of cardiac-derived cells as cardiospheres mimics stem cell niche properties, with enhanced “stemness” and expression of ECM and adhesion molecules. These changes underlie an increase in cell survival and more potent augmentation of global function following implantation into the infarcted heart.

The efficiency of stem cell transplantation is limited by low cell retention. Intracoronary (IC) delivery is convenient and widely used but exhibits particularly low cell retention rates. We sought to improve IC cell retention by magnetic targeting. Rat cardiosphere-derived cells labeled with iron microspheres were injected into the left ventricular cavity of syngeneic rats during brief aortic clamping. Placement of a 1.3 Tesla magnet ~1 cm above the heart during and after cell injection enhanced cell retention at 24 h by 5.2–6.4-fold when 1, 3, or 5 × 105 cells were infused, without elevation of serum troponin I (sTnI) levels. Higher cell doses (1 or 2 × 106 cells) did raise sTnI levels, due to microvascular obstruction; in this range, magnetic enhancement did not improve cell retention. To assess efficacy, 5 × 105 iron-labeled, GFP-expressing cells were infused into rat hearts after 45 min ischemia/20 min reperfusion of the left anterior coronary artery, with and without a superimposed magnet. By quantitative PCR and optical imaging, magnetic targeting increased cardiac retention of transplanted cells at 24 h, and decreased migration into the lungs. The enhanced cell engraftment persisted for at least 3 weeks, at which time left ventricular remodeling was attenuated, and therapeutic benefit (ejection fraction) was higher, in the magnetic targeting group. Histology revealed more GFP+ cardiomyocytes, Ki67+ cardiomyocytes and GFP−/ckit+ cells, and fewer TUNEL+ cells, in hearts from the magnetic targeting group. In a rat model of ischemia/reperfusion injury, magnetically enhanced intracoronary cell delivery is safe and improves cell therapy outcomes.

A self‐measured home blood pressure (BP)‐guided strategy is an effective practical approach to hypertension management. The Asia BP@Home study is the first designed to investigate current home BP control status in different Asian countries/regions using standardized home BP measurements taken with the same validated home BP monitoring device with data memory. We enrolled 1443 medicated hypertensive patients from 15 Asian specialist centers in 11 countries/regions between April 2017 and March 2018. BP was relatively well controlled in 68.2% of patients using a morning home systolic BP (SBP) cutoff of <135 mm Hg, and in 55.1% of patients using a clinic SBP cutoff of <140 mm Hg. When cutoff values were changed to the 2017 AHA/ACC threshold (SBP <130 mm Hg), 53.6% of patients were well controlled for morning home SBP. Using clinic 140 mm Hg and morning home 135 mm Hg SBP thresholds, the proportion of patients with well‐controlled hypertension (46%) was higher than for uncontrolled sustained (22%), white‐coat (23%), and masked uncontrolled (9%) hypertension, with significant country/regional differences. Home BP variability in Asian countries was high, and varied by country/region. In conclusion, the Asia BP@Home study demonstrated that home BP is relatively well controlled at hypertension specialist centers in Asia. However, almost half of patients remain uncontrolled for morning BP according to new guidelines, with significant country/regional differences. Strict home BP control should be beneficial in Asian populations. The findings of this study are important to facilitate development of health policies focused on reducing cardiovascular complications in Asia.

SUMMARYThe aim of the present study was to evaluate levels of soluble CD 163 in sera and fluids from rheumatoid arthritis (RA) patients and elucidate the mechanism that regulates the shedding of CD163. Levels of soluble CD163 in sera and fluids from RA patients were examined by a sandwich enzyme immunoassay and Western blotting. To determine the effects of tissue inhibitors of metalloproteinase (TIMPs) on the shedding of CD163 from monocytes/macrophages, levels of soluble CD163 in cultures of monocytes/ macrophages and the expression of CD163 on monocytes/macrophages in the presence or absence of TIMPs were examined by a sandwich enzyme immunoassay and flow cytometry, respectively. The clinical marker that was most associated with serum levels of soluble CD163 was levels of CRP. TIMP-3, but not TIMP-1 or TIMP-2, inhibited the shedding of CD163 from monocytes/macrophages. It was shown that serum levels of soluble CD163 are a sensitive and reliable marker to monitor activated macrophages in synovitis from RA patients and the results imply that the responsible proteinase for the shedding of CD163 is not a member of the matrix metalloproteinases, but is likely to be a member of ADAMs.