Yerem Yeghiazarians

University of California, San Francisco, San Francisco, California, United States

Are you Yerem Yeghiazarians?

Claim your profile

Publications (102)476.36 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We have generated a bioinspired tunable system of hyaluronic acid (HyA)-based hydrogels for Matrix-Assisted Cell Transplantation (MACT). With this material, we have independently evaluated matrix parameters such as adhesion peptide density, mechanical properties, and growth factor sequestering capacity, to engineer an environment that imbues donor cells with a milieu that promotes survival and engraftment with host tissues after transplantation. Using a versatile population of Sca-1+/CD45− cardiac progenitor cells (CPCs), we demonstrated that the addition of heparin in the HyA hydrogels was necessary to coordinate the presentation of TGFβ1 and to support the trophic functions of the CPCs via endothelial cell differentiation and vascular like tubular network formation. Presentation of exogenous TGFβ1 by binding with heparin improved differentiated CPC function by sequestering additional endogenously-produced angiogenic factors. Finally, we demonstrated that TGFβ1 and heparin-containing HyA hydrogels can promote CPC survival when implanted subcutaneously into murine hind-limbs and encouraged their participation in the ensuing neovascular response, which included blood vessels that had anastomosed with the host's blood vessels.
    Biomaterials 04/2015; 47. DOI:10.1016/j.biomaterials.2014.12.043 · 8.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypoxia-inducible gene domain family member 1A (HIGD1A) is a survival factor induced by hypoxia-inducible factor 1 (HIF-1). HIF-1 regulates many responses to oxygen deprivation, but viable cells within hypoxic perinecrotic solid tumor regions frequently lack HIF-1α. HIGD1A is induced in these HIF-deficient extreme environments and interacts with the mitochondrial electron transport chain to repress oxygen consumption, enhance AMPK activity, and lower cellular ROS levels. Importantly, HIGD1A decreases tumor growth but promotes tumor cell survival in vivo. The human Higd1a gene is located on chromosome 3p22.1, where many tumor suppressor genes reside. Consistent with this, the Higd1a gene promoter is differentially methylated in human cancers, preventing its hypoxic induction. However, when hypoxic tumor cells are confronted with glucose deprivation, DNA methyltransferase activity is inhibited, enabling HIGD1A expression, metabolic adaptation, and possible dormancy induction. Our findings therefore reveal important new roles for this family of mitochondrial proteins in cancer biology. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lipid accumulation in the heart is associated with obesity and diabetes and may play an important role in the pathogenesis of heart failure. The renin-angiotensin system is also thought to contribute to cardiovascular morbidity in obese and diabetic patients. We hypothesized that the presence of lipid within the myocyte might potentiate the cardiomyopathic effects of angiotensin II in the cardiac diacylglycerol acyl transferase 1 (DGAT1) transgenic mouse model of myocyte steatosis. Treatment with angiotensin II resulted in a similar increase in blood pressure in both nontransgenic and DGAT1 transgenic mice. However, angiotensin II in the DGAT1 transgenic mice resulted in a marked increase in interstitial fibrosis and a reduction in systolic function compared to nontransgenic littermates. Lipidomic analysis revealed that over 20% of lipid species were significantly altered between NTg and DGAT1 animals while 3% were responsive to angiotensin II administration. Reactive oxygen species were also increased by angiotensin II in the DGAT1 transgenic heart. Angiotensin II treatment resulted in increased expression of transforming growth factor beta 2 (TGFβ2) and the type I TGFβ receptor, as well as increased phosphorylation of SMAD2 in the DGAT1 transgenic heart. Injection of neutralizing antibodies to TGFβ resulted in a reduction in fibrosis in the DGAT1 transgenic hearts treated with angiotensin II. These results suggest that myocyte steatosis amplifies the fibrotic effects of angiotensin II through mechanisms that involve activation of TGFβ signaling and increased production of reactive oxygen species. Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 12/2014; DOI:10.1152/ajpheart.00742.2014 · 4.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent advances in technology have led to an increase in the use of bilateral femoral artery access and the requirement for large-bore access. Optimal access is in the common femoral artery (CFA), rather than higher (in the external iliac artery) or lower (in one of the branches of the CFA). However, there is a paucity of data in the literature about the relationship between bifurcation level of one CFA and the contralateral CFA. To define the prevalence of high bifurcation of the CFA and the relationship between bifurcation level on both sides, we performed a retrospective analysis of all patients with bilateral femoral angiography. From 4880 femoral angiograms performed at UCSF cardiac catheterization laboratory between 2005-2013, a total of 273 patients had bilateral femoral angiograms. The prevalence of low/normal, high, and very-high femoral bifurcations was 70%, 26%, and 4%, respectively, with no difference between sides. A high or very-high bifurcation significantly increased the likelihood of a high bifurcation on the contralateral side (odds ratio >3.0). Multivariable logistic regression analysis revealed age, gender, self-reported race, height, weight, and body mass index were not predictive of high or very-high bifurcations on either side. In conclusion, high femoral artery bifurcations are common and increase the likelihood of a high bifurcation of the contralateral femoral artery.
    The Journal of invasive cardiology 09/2014; 26(9):409-412. · 0.82 Impact Factor
  • International Journal of Cardiology 08/2014; DOI:10.1016/j.ijcard.2014.08.096 · 6.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Coronary artery aneurysm (CAA) is an uncommon clinical finding, with an incidence varying from 1.5%-4.9% in adults, and is usually considered a variant of coronary artery disease (CAD). CAA identified in the context of acute coronary syndrome (ACS) represents a unique management challenge, particularly if the morphology of the CAA is suspected to have provoked the acute clinical syndrome. CAA is associated with thrombus formation due to abnormal laminar flow, as well as abnormal platelet and endothelial-derived pathophysiologic factors within the CAA. Once formed, mural thrombus may potentiate the deposition of additional thrombus within aneurysmal segments. Percutaneous revascularization of CAA has been associated with complications including distal embolization of thrombus, no-reflow phenomenon, stent malapposition, dissection, and rupture. Presently, there are no formal guidelines to direct the management of CAA in patients presenting with ACS; controversies exist whether conservative, surgical, or catheter-based management should be pursued. In this manuscript, we present an extensive review of the existing literature and associated clinical guidelines, and propose a management algorithm for patients with this complex clinical scenario. Armed with this perspective, therapeutic decisions may be tailored to synthesize patient factors and preferences, individualized clinical assessment, and existing American Heart Association/American College of Cardiology guidelines for management of ACS.
    The Journal of invasive cardiology 06/2014; 26(6):283-290. · 0.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: : Cardiovascular disease is the leading cause of death in Western countries. A major limitation of current treatments is the inability to efficiently repair or replace dead myocardium. Recently, stem cell-based therapies have been explored as an avenue to circumvent current therapeutic limitations. Overall, these therapies seem to result in small improvements in the contractile function of the heart. The exact mechanism(s) of action that underlie these improvements remain unknown, and it is believed that paracrine effects play a significant role. Previously, we had reported that an extract derived from bone marrow cells, in the absence of any live cell, contained cardioprotective soluble factors. In this study, we identify IL-15 as a putative cardioprotectant within the bone marrow cells paracrine profile. Using an in vitro culture system, we assessed the ability of IL-15 to protect cardiomyocytes under hypoxic conditions. For the first time, we have identified IL-15 receptors on the surface of cardiomyocytes and delineated the signaling system by which hypoxic cardiomyocytes may be protected from cellular death and rescued from oxidative stress with IL-15 treatment.
    Journal of cardiovascular pharmacology 05/2014; 63(5):406-411. DOI:10.1097/FJC.0000000000000061 · 2.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cardiac catheterization has been increasingly utilized to evaluate coronary artery disease in patients with end stage liver disease (ESLD). It is known in other populations that radial access reduces access site complications;however, there is a paucity of data in ESLD patients. We investigated vascular and bleeding complications rates between trans-femoral and trans-radial cardiac catheterizations in this high risk population. In this retrospective cohort study, three hundred and thirty four ESLD patients were identified between August 2004 and December 2012 who had undergone trans-femoral (femoral group) or trans-radial (radial group) cardiac catheterizations at our institution. The radial group was not significantly different from the femoral group in age (p = 0.056), proportions of genders (p = 0.85), and weight (p = 0.19); however, compared to the femoral group, the radial group had significantly lower blood pressure (p < 0.0001), hemoglobin (10.4 ± 1.9 vs 11.1 ± 2.02 g/dL, p = 0.001), and hematocrit (30.3 ± 5.7% vs 32.6 ± 6.0%, p < 0.0006), and had a significantly higher INR (1.94 ± 1.16 vs 1.59 ± 0.62, p = 0.0001). In terms of vascular complications, the radial group had a significantly lower rate of pseudoaneurysms (0% vs 3.7%, p = 0.019) than the femoral group. While there were no bleeding complications in either group or differences in transfusion requirements, there was a significantly lower percentage drop in hematocrit in the radial group compared to the femoral group (5.4% vs 7.8%, p = 0.039). In conclusion, trans-radial catheterization is associated with lower rates of vascular access site complications compared to trans-femoral catheterization.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aging is associated with higher incidence of heart failure and death following myocardial infarction (MI). The molecular and cellular changes that lead to these worse outcomes are not known. Young and aging mice underwent induction of MI by LAD ligation. There was a significant increase in mortality in the aging mice. Neither the young nor aging hearts after MI had inducible ventricular tachycardia. Cardiomyocyte apoptosis increases early after MI in young and aging mice, but to a much greater degree in the aging mice. Caspase inhibition with Ac-DEVD-CHO resulted in a 61% reduction in activated caspase-3 and an 84% reduction in apoptosis in cardiomyocytes in young mice (P < 0.05), but not in aging mice. Gene pathway profiling demonstrated activation of both the caspase and Map3k1/Mapk10 pathways in aging mice following MI, which may contribute to their resistance to caspase inhibition. Aging hearts activate distinct apoptotic pathways have more cardiomyocyte apoptosis and are resistant to antiapoptotic therapies following MI. Novel or combination approaches may be required to improve outcomes in aging patients following MI.
    Cardiovascular Therapeutics 12/2013; 31(6):e102-10. DOI:10.1111/1755-5922.12043 · 2.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Current evidence suggests that regenerative v. degenerative endothelial responses can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity. We have previously shown that a cocoa flavanol (CF) intervention can improve endothelial function and increase the regenerative capacity of the endothelium by mobilising circulating angiogenic cells in patients with coronary artery disease (CAD). The aim of the present study was to investigate whether CF can lower the levels of circulating endothelial microparticles (EMP), markers of endothelial integrity, along with improvements in endothelial function. The levels of EMP in the frozen plasma samples of CAD patients were measured along with endothelial function (flow-mediated vasodilation, FMD); n 16, FMD data published previously), and these data were compared with those of young (n 12) and age-matched (n 12) healthy control subjects. The CAD patients exhibited significantly increased levels of EMP along with impaired FMD when compared with the healthy control subjects. The levels of CD144+ and CD31+/41- EMP were inversely correlated with FMD (r - 0·67, P= 0·01 and r - 0·59, P= 0·01, respectively). In these CAD patients, the levels of EMP were measured after they had consumed a drink containing 375 mg of CF (high-CF intervention, HiFI) or 9 mg of CF (macro- and micronutrient-matched low-CF control, LoFl) twice daily over a 30-d period in a randomised, double-blind, cross-over study. After 1 month of HiFI, the levels of CD31+/41- and CD144+ EMP decreased ( - 25 and - 23 %, respectively), but not after LoFl. Our data show that flavanols lower the levels of EMP along with higher endothelial function, lending evidence to the novel concept that flavanols may improve endothelial integrity.
    The British journal of nutrition 11/2013; 111(07):1-8. DOI:10.1017/S0007114513003693 · 3.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Transradial access (TRA) offers advantages including decreased vascular complications, reduced length of hospital stay, and reduced cost. The size of the radial artery (RA) limits the equipment that can be used via TRA. Intra-arterial (IA) vasodilators prevent and treat RA spasm, yet are not uniformly used in TRA and their effect on the absolute size of the RA remains unknown. 121 patients undergoing TRA for cardiac catheterization were included. 78 patients underwent RA angiography prior to administration of IA vasodilators ('no vasodilator' group), 43 patients underwent radial angiography after administration of an IA verapamil and nitroglycerin cocktail ('vasodilator' group). Quantitative angiography was used to compare the RA diameters. Clinical characteristics were similar between the groups, except that patients in the 'no vasodilator' cohort were taller (1.67±0.1m vs. 1.73±0.1m, p=0.002), and heavier (84.9±18.2kg vs. 75±17.1kg, p=0.003). In the 'vasodilator' group the proximal RA diameter was larger (2.29±0.47mm vs. 2.09±0.41mm, p=0.02) as was the narrowest segment (1.83±0.56mm vs 1.39±0.43, p<0.0001) compared to the 'no vasodilator' group. At the RA origin, 79.4% of those in the 'vasodilator' group were larger than a 6Fr guide catheter, compared to 51.4% in the 'no vasodilator' group (p=0.004). At the narrowest segment a higher percentage of RAs in the 'vasodilator' group were larger than a 5Fr guide catheter (65.1% vs 26.9%, p<0.001) and a 6Fr catheter (34.9% vs 10.3%, p=0.001). IA vasodilators increase pre-procedural RA diameter in patients undergoing cardiac catheterization via TRA. This increase in diameter has important implications for procedural planning. Boyer et al. performed a blinded controlled clinical trial investigating the effects of intra-arterial vasodilators on radial artery size and spasm during cardiac catheterization. The study demonstrates that intra-arterial vasodilators significantly increased the radial artery size throughout the entire course of the vessel and significantly decreased the amount of radial artery spasm. The authors conclude that these findings support the use of intra-arterial vasodilators during cardiac catheterization and have important implications for emerging technologies such as larger bore sheathless radial procedures.
    Cardiovascular revascularization medicine: including molecular interventions 10/2013; DOI:10.1016/j.carrev.2013.08.009
  • 09/2013; 2(3):103-114. DOI:10.3390/jcm2030103
  • Jianqin Ye, Yerem Yeghiazarians
    [Show abstract] [Hide abstract]
    ABSTRACT: Various stem cell types have been tested for regenerating damaged myocardium after myocardial infarction. However, the results of clinical trials have not been consistent, with only some of the trials reporting small improvements in cardiac function. It appears that engraftment and survival of injected cells is limited, and transplanted stem cells either do not differentiate into cardiac cells or differentiate into only limited number of cardiac cells. The exact mechanism(s) of cardiac functional improvement by cell therapy are unclear, but paracrine effect may play a central role. The resident cardiac progenitor cells identified within the adult myocardium have distinct advantages over other stem cell types for cardiac cell therapy, as they are likely pre-committed to the cardiovascular fate. However, isolating and expanding these cells from cardiac biopsies is a challenge. More recently, direct reprogramming of fibroblasts into cardiomyocytes has given new hope for myocardial regeneration. Here we will review different stem cells used in cardiac cell therapy with a focus on the native cardiac progenitor cells and briefly outline future directions of cardiac cell therapy.
    Journal of cardiovascular pharmacology 05/2013; DOI:10.1097/FJC.0b013e318299ebc0 · 2.11 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cellular stress responses are frequently governed by the subcellular localization of critical effector proteins. Apoptosis-inducing Factor (AIF) or Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH), for example, can translocate from mitochondria to the nucleus, where they modulate apoptotic death pathways. Hypoxia-inducible gene domain 1A (HIGD1A) is a mitochondrial protein regulated by Hypoxia-inducible Factor-1α (HIF1α). Here we show that while HIGD1A resides in mitochondria during physiological hypoxia, severe metabolic stress, such as glucose starvation coupled with hypoxia, in addition to DNA damage induced by etoposide, triggers its nuclear accumulation. We show that nuclear localization of HIGD1A overlaps with that of AIF, and is dependent on the presence of BAX and BAK. Furthermore, we show that AIF and HIGD1A physically interact. Additionally, we demonstrate that nuclear HIGD1A is a potential marker of metabolic stress in vivo, frequently observed in diverse pathological states such as myocardial infarction, hypoxic-ischemic encephalopathy (HIE), and different types of cancer. In summary, we demonstrate a novel nuclear localization of HIGD1A that is commonly observed in human disease processes in vivo.
    PLoS ONE 04/2013; 8(4):e62758. DOI:10.1371/journal.pone.0062758 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND/OBJECTIVES: Transradial access (TRA) is being increasingly used for both diagnostic and interventional cardiac procedures. Use of TRA offers many advantages: decreased bleeding, vascular complications, reduced length of hospital stay, and reduced cost. However, the small size of the radial artery limits the size of the equipment that can be used via this approach. We sought to determine whether pre-procedural administration of topical nitroglycerin and lidocaine increases the size of the radial artery. METHODS: Patients undergoing transradial cardiac catheterization were randomized in a double-blind fashion to a topical combination of nitroglycerin+lidocaine or placebo ointment. The primary endpoint was change in radial artery size. Secondary endpoints included radial artery spasm and radial artery patency. RESULTS: 86 patients were enrolled (43 allocated to treatment group and 43 to placebo group). Patients underwent ultrasound of the radial artery at baseline and before the catheterization. Complications were rare: one hematoma (placebo group) and one radial artery occlusion (placebo group). Baseline demographic and clinical characteristics were similar. The baseline radial artery cross-sectional area (CSA) was similar in both groups (4.95±0.24mm(2) in placebo group and 5.14±0.34mm(2) in the treatment group). However, the final CSA decreased to 4.66±0.25mm(2) in the placebo group and increased to 5.78±0.38mm(2) in the treatment group (p=0.02), which corresponded to a decrease in CSA by -5.6±2.1% and an increase in CSA by 16.5±4.2% (p<0.0001), respectively. CONCLUSIONS: Pre-procedural administration of topical mixture of nitroglycerin+lidocaine increases the size of the radial artery in patients undergoing transradial cardiac catheterization. CLINICALTRIALS.GOV IDENTIFIER: NCT01155167.
    International journal of cardiology 04/2013; 168(3). DOI:10.1016/j.ijcard.2013.03.048 · 6.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pulmonary hypertension (PH) is a fatal disease with no treatment options characterized by elevated pulmonary vascular resistance and secondary right ventricular failure. The etiology of PAH is multiple and its pathogenesis is complex. Although the exact role of cellular microparticles (MPs) remains partially understood, there is increasing evidence to suggest an active role for MPs in PH pathophysiology. Patients with PH exhibited higher circulating levels of MPs compared to controls subjects and in vitro or in vivo generated MPs can induce endothelial dysfunction, interfere with coagulation pathways or modulate inflammatory phenomenon. Whether or not these new conveyors of biological information contribute to the acquisition and/or maintenance to the altered endothelial phenotype is unexplored in PH and requires further study.
    European Respiratory Journal 12/2012; 42(1). DOI:10.1183/09031936.00087212 · 7.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The cardiosphere (CS) is composed of a heterogeneous population of cells, including CD45(+) cells that are bone marrow (BM)-derived. However, whether the CD45(+) cells are an essential cell component in CS formation is unknown. The current study was undertaken to address this question. Cardiospheres (CSs) were harvested from 1-week post-myocardial infarction (MI) or non-MI hearts of C57BL/6 J mice. The process of CS formation was observed by timelapse photography. To analyze the role of BM-derived CD45(+) cells in CS formation, CD45(+) cells were depleted from populations of CS-forming cells by immunomagnetic beads. We recorded the number of CSs formed in culture from the same amount (10(5)) of intact CS-forming cells, from CD45(+)-cell-depleted CS-forming cells and from CD45(+) cells alone (n=6-9/cell type). CS-forming cells selectively aggregated together to form CSs by 35 h after plating. The depletion of CD45(+) cells from CS-forming cells actually increased the formation of CSs (67±10 CSs/10(5) cells) compared with non-depleted CS-forming cells (51±6 CSs/10(5) cells, P<0.0001). Purified CD45(+) cells from CS-forming cells did not form CSs in culture. Thus, BM-derived CD45(+) cells including BM progenitors are neither necessary nor sufficient for CS formation.
    Cell and Tissue Research 10/2012; 351(1). DOI:10.1007/s00441-012-1511-8 · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Small radial artery diameter (RAD) and vasospasm are barriers to radial artery cannulation. We performed this study to determine if topical nitroglycerin and/or nitroglycerin plus topical lidocaine increases RAD without affecting systemic blood pressure. This was a randomized, double-blind, placebo-controlled study. In the first visit, to determine the optimal dose of nitroglycerin, subjects were randomized to either 15 or 30 mg nitroglycerin on one wrist and placebo on the other. In visit 2, to assess for any effect of lidocaine on the vasodilator function of nitroglycerin, the same subjects were randomized to 20 mg lidocaine + 30 mg nitroglycerin vs 20 mg lidocaine + placebo, or 40 mg lidocaine + 30 mg nitroglycerin vs 40 mg lidocaine + placebo. In both visits, blood pressure and RAD using ultrasonography were measured for 2 hours. In visit 1, both nitroglycerin groups significantly increased RAD, with greater increases with 30 mg nitroglycerin (P < .01) and no significant increase in RAD in placebo wrists. In visit 2, increase in RAD was significantly greater with 20 mg lidocaine + 30 mg nitroglycerin vs 20 mg lidocaine + placebo (P < .001), and 40 mg lidocaine + 30 mg nitroglycerin vs 40 mg lidocaine + placebo (P < .001), indicating that lidocaine does not alter the effect of nitroglycerin. There were significant increases in RAD seen as early as 30 minutes. There were no significant change in RAD in lidocaine + placebo-treated wrists and no change in blood pressure in any group. Topical nitroglycerin and lidocaine significantly increase RAD within 30 to 60 minutes with no effect on contralateral radial artery or blood pressure, indicating a direct, local effect on the radial artery. ( number NCT00686231).
    Journal of critical care 06/2012; 27(5):532.e9-532.e13. DOI:10.1016/j.jcrc.2012.04.019 · 2.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We have previously shown that mouse whole bone marrow cell (BMC) extract results in improvement of cardiac function and decreases scar size in a mouse model of myocardial infarction (MI), in the absence of intact cells. It is not clear if these results are translatable to extracts from human BMC (hBMC) or mononuclear cells (hMNC), which would have significant clinical implications. Male C57BL/6J (10-12 weeks old) mice were included in this study. MI was created by permanent ligation of the left anterior descending artery. Animals were randomized into three groups to receive ultrasound-guided myocardial injections with either hBMCs extract (n=6), hMNCs extract (n=8) or control with 0.5% bovine serum albumin (BSA) (n=7). Cardiac function was assessed by echocardiography at baseline, 2 and 28 days post-MI. Infarct size and vascularity was assessed at 28 days post-MI. hBMC and hMNC extract preserve cardiac function and result in smaller scar size post-MI when compared with the control group. The current study for the first time reports that hBMC and hMNC extracts improve cardiac function post-MI in a mouse MI model. Further studies are necessary to fully address the potential clinical benefits of these therapies.
    The Open Cardiovascular Medicine Journal 04/2012; 6:38-43. DOI:10.2174/1874192401206010038
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and objectives. Clinical trials of bone-marrow (BM)-derived cells for therapy after acute myocardial infarct (MI) have been controversial. The most commonly used cells for these trials have been mononuclear cells (MNC), obtained by fractionation of BM cells (BMCs) via different protocols. In this study, we performed a head-to-head comparison of: 1) whole BMC; 2) fractionated BM (fBM) using the commonly used Ficoll protocol; 3) the extract derived from the fBM (fBM extract) versus 4) saline (HBSS) control for treatment of acute MI. Methods. In total, 155 male C57BL/6J (10-12-week old) mice were included. Echocardiography was performed at baseline and 2 days after permanent ligation of the left anterior descending artery to induce MI. Echocardiography and histology were employed to measure outcome at 28 days post-MI. Results. Whole BMC therapy improved left ventricular ejection fraction (LVEF) post-MI, but fBM or fBM extract was not beneficial compared to control (change of LVEF of 4.9% ±4.6% (P = 0.02), -0.4% ±5.8% (P = 0.86), -2.0% ±6.2% (P = 0.97) versus -1.4% ±5.3%, respectively). The histological infarct size or numbers of arterioles or capillaries at infarct or border zone did not differ between the groups. Conclusions. Clinical studies should be performed to test whether whole BMC therapy translates into better outcome also after human MI.
    Annals of Medicine 04/2012; DOI:10.3109/07853890.2012.672026 · 4.73 Impact Factor

Publication Stats

2k Citations
476.36 Total Impact Points


  • 2005–2015
    • University of California, San Francisco
      • • Broad Center of Regeneration Medicine and Stem Cell Research
      • • Division of Cardiology
      San Francisco, California, United States
  • 2013
    • CSU Mentor
      Long Beach, California, United States
  • 2000–2008
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2007
    • St. Louis Heart and Vascular Cardiology
      San Luis, Missouri, United States
  • 2006
    • Brigham and Women's Hospital
      Boston, Massachusetts, United States
  • 2003
    • Northeastern University
      • Department of Mechanical and Industrial Engineering
      Boston, Massachusetts, United States