Abstract 81: End-Stage Human Failing Heart Increases Functional Cardiac Progenitor Cells

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Rachana Mishra ◽  
David Simpson ◽  
Sudhish Sharma ◽  
Evan Colletti ◽  
Sunjay Kaushal
Keyword(s):  
Progenitor Cells ◽  
Fold Increase ◽  
Myosin Heavy Chain Isoforms ◽  
Functional Improvement ◽  
Cardiac Progenitor Cells ◽  
Failing Heart ◽  
Normal Human ◽  
Fetal Reprogramming ◽  
The Right ◽  
End Stage

Background: Human cases of end-stage heart failure provide the rare opportunity to test whether the cells within these hearts exhibit different phenotypic characteristics than those in healthy hearts. We tested whether the failing heart, as it reverses to a well-known fetal reprogramming state, also compensates by increasing the number of functional cardiac progenitor cells. Methods and Results: We examined samples from end-stage human failing hearts and also normal human hearts to quantitate the expression of various cardiac progenitor markers, by immunofluorescence, flow cytometry and RT-PCR. We further tested whether the cardiac progenitor cells were functional in a rodent model of myocardial infarction. All the failing end-stage hearts (N=13) reversed to a fetal state by switching their myosin heavy chain isoforms from beta to alpha. Additionally, atrial natriuretic factor was increased. Compared to normal congenital myocardium, failing end-stage hearts had a 2 to 5 fold increase in the number of C-kit+ and ISL-1+ cardiac progenitor cells (P<0.5). The numbers of cardiac progenitor cells was highest in the right atria as compared to other chambers of the end-stage heart. Cardiac progenitor cells isolated from failing hearts expressed several stemness markers that were upregulated compared to normal human hearts. FACS and IF analysis demonstrated significantly (P<0.5) higher c-kit expression in CDCs derived from end stage patients compare to normal congenital myocardium. Also, there was a tendency for increased FLK1 and Sca-1 expression in CM patients respectively. Transplanted cardiac progenitor cells from end-stage hearts promoted greater myocardial regeneration and functional improvement in the infarcted rat myocardium than transplanted cardiac progenitor cells derived from normal congenital patients (EF=57+3 vs. 41.5±3, P<0.05). Conclusion: Our results show an increase of progenitor cells within the end-stage heart that have the functional potential to regenerate the myocardium. Stimulating the differentiation and increasing the population of cardiac progenitor cells may provide a novel therapeutic strategy for these end-stage hearts.

Abstract 18698: Identification of a Novel Cardiac Progenitor Population Expressing Pw1/peg3 in the Murine Heart

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Elisa Yaniz-Galende ◽  
Luigi Formicola ◽  
Nathalie Mougenot ◽  
Lise Legrand ◽  
Jiqiu Chen ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Fold Increase ◽  
Cardiac Regeneration ◽  
Cardiac Repair ◽  
Cardiac Progenitor Cells ◽  
Average Percentage ◽  
Pathological Conditions ◽  
Reporter Mice ◽  
Novel Target

The myocardium responds to injury by recruiting cardiac progenitor cells (CPCs) to the injured tissue to promote cardiac repair. Although different classes of CPCs have been identified, their contribution in physiological and pathological conditions remains unclear. PW1 gene has recently been proposed as a marker of resident adult stem and progenitor cell populations in several adult tissues. Our goal was to characterize and determine the role of PW1+ population in the heart. Here, we employ immunostaining and fluorescence-activated cell sorting (FACS) analysis in PW1-reporter mouse to perform qualitative and quantitative analyses of PW1+ population in the heart. We first found that PW1+ cells are mainly located in the epicardium and myocardial interstitium of normal hearts. The average percentage of PW1+ cells, as assessed by FACS, was 1.56±1.41%. A subset of PW1+ cells also co-express other CPC markers such as Sca-1 (52±22%) or PDGFR1α (43±14%). In contrast, a very small proportion of PW1+ cells co-express c-kit (6±5%). To investigate the contribution of PW1+ cells in pathological conditions, we then performed myocardial infarction (MI) by LAD ligation in PW1-reporter mice. We found that MI resulted in a 3-fold increase in the number of PW1+ cells in infarcted mice compared with sham-operated groups, at 1 week post-MI (1.16%±0.47% in sham versus 3.43%±0.82 in MI). This population preferentially localized in the injured myocardium and border area. PW1+ cells were isolated by FACS from the whole infarcted heart from PW1-reporter mice. In vitro differentiation assays reveal that purified PW1+ cells are multipotent and can spontaneously differentiate into smooth muscle cells, endothelial cells and cardiomyocyte-like cells. Taken together, our data identify a novel PW1+ cardiac progenitor population with the potential to undergo differentiation into multiple cardiac lineages, suggesting their involvement in cardiac repair in normal and pathological conditions. The discovery of a novel population of cardiac progenitor cells, augmented following MI and with cardiogenic potential, provides a novel target for therapeutic approaches aimed at improving cardiac regeneration.

scholarly journals Activation of Cardiac Progenitor Cells Reverses the Failing Heart Senescent Phenotype and Prolongs Lifespan

2008 ◽  
Vol 102 (5) ◽  
pp. 597-606 ◽  
Author(s):  
Arantxa Gonzalez ◽  
Marcello Rota ◽  
Daria Nurzynska ◽  
Yu Misao ◽  
Jochen Tillmanns ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cardiac Progenitor Cells ◽  
Failing Heart ◽  
Senescent Phenotype

Abstract 3815: Pim-1 Gene Delivery to Cardiac Progenitor Cells Prevents Long Term Cardiac Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kimberlee Fischer ◽  
Weitao Wu ◽  
Christopher Cottage ◽  
Natalie Gude ◽  
Mark Sussman
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Left Ventricular ◽  
Functional Improvement ◽  
Cardiac Progenitor Cells ◽  
Intramyocardial Injection ◽  
Improved Performance ◽  
Enhance Stem Cell ◽  
Fractional Shortening

Cardiac stem cell therapy administered at the time of infarction effectively blunts cardiomyopathic damage a few weeks after treatment but long term efficacy of adoptive stem cell transfer remains largely unknown. A comparative analysis shows that long term (25 week) protection is only provided by Pim-1 modified progenitor cells whereas unmodified progenitor cells fail to provide prolonged benefits after six weeks post intramyocardial injection. After infarction mice were intramyocardially injected with saline, unmodified cardiac progenitor cells (CPC’s), or Pim-1 modified CPC’s. At a 12 week time point mice injected with Pim-1 modified CPC’s have increased EF and FS as compared to mice injected with unmodified cells (n=15 for each group). Invasive hemodynamic measurements (n=5 for each group) confirm that mice injected with Pim-1 modified CPC’s had improved performance by assessment of multiple functional criteria compared to unmodified cells. Longitudinal monitoring by echocardiography reveals that mice injected with Pim-1 modified CPC’s sustain fractional shortening and ejection fraction for up to 24 weeks whereas animals that receive unmodified cells begin to fail within 6 weeks after delivery and were not statistically different than saline injected controls after 12 weeks. In addition Pim-1 CPC injected mice had infarct sizes 52% smaller than control groups (p<.02). Both saline and unmodified CPC’s groups maintained similar infarct sizes (~60% of left ventricular free wall). Confocal microscopy reveals engraftment and persistence of injected Pim-1 CPC’s into the myocardium with differentiation into multiple cardiogenic lineages giving rise to myocytes, vasculature, and endothelium Successful long term functional improvement of the heart requires the engraftment of Pim-1 genetically modified cardiac progenitor cells. Unmodified cells offer an acute ameliorative response but ultimately fail in the ability to effectively repair and maintain the function of the heart. These results support use of genetic engineering to enhance stem cell-mediated myocardial regeneration.

scholarly journals Potential of mesenchymal- and cardiac progenitor cells for therapeutic targeting of B-cells and antibody responses in end-stage heart failure

PLoS ONE ◽  
2019 ◽  
Vol 14 (12) ◽  
pp. e0227283 ◽  
Author(s):  
Patricia van den Hoogen ◽  
Saskia C. A. de Jager ◽  
Emma A. Mol ◽  
Arjan S. Schoneveld ◽  
Manon M. H. Huibers ◽  
...  
Keyword(s):  
Heart Failure ◽  
B Cells ◽  
Progenitor Cells ◽  
Antibody Responses ◽  
Cardiac Progenitor Cells ◽  
Therapeutic Targeting ◽  
End Stage Heart Failure ◽  
End Stage

Abstract 238: Role of Erythropoietin Signaling in the Biology of Mouse Cardiac Progenitor Cells

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Maria P Zafiriou ◽  
Claudia Noack ◽  
Michael Didie ◽  
Bernhard Unsoeld ◽  
Ali El-Armouche ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Activation ◽  
Ischemia Reperfusion ◽  
Cardiac Cells ◽  
Functional Improvement ◽  
Cardiac Progenitor Cells ◽  
Epor Expression

Erythropoietin (Epo) was shown to improve cardiac function following ischemia reperfusion mainly via neo-angiogenesis and anti-apoptotic mechanisms. We found EpoR expression to be particularly high in adult cardiac progenitor cells (CPCs). Thus, we reasoned that Epo may play a role in the biology of these cells. We isolated CPCs from adult C57BL/6 hearts by enzymatic digestion and filtration (pore size: 30 µm). By means of immunofluorescence microscopy (IF) and flow cytometry (FC) we analyzed EpoR expression in the CPCs. 24±3% of the investigated cardiac cells were positive for EpoR with 3±2% of these being c-kit+ and 28%±2% Sca-1+. 52% of the EpoR+ cells expressed endothelial cell markers (40±2% CD34+, 9±2% FLK1+). 42±4% expressed myocyte markers (αMHC+, cTNT+). IF revealed a progenitor-like population with immature cell morphology and proliferation potential (ki67+). Cell cycle analysis showed an enrichment of αMHC+ EpoR+ cells in S and G2 phase (49±7%, n=3) as compared to the αMHC- EpoR- population (13±3%, n=3). Moreover, we tested the effect of Epo in the biology of these CPCs in vitro. At d14 we observed a two-fold increase of GATA4+ and cTnT+ cardiac cells in the co-cultures treated with Epo (n=3). CPC cycle arrest abrogated the aforementioned effects, suggesting that Epo influences mainly CPC proliferation. Finally, we tested the potential of Epo to protect against ischemia by inducing the proliferation of these αMHC+ CPCs in vivo in a myocardial infarction (MI) model. 4 weeks post MI, echocardiography did not reveal a significant functional improvement of the Epo receiving mice (2x, 2U/g Epo i.p). Nevertheless, FC analysis of the progenitor pool showed a significant augmentation of αMHC+ and cTnT+ cells (Sham: 19±3% vs Epo 35±3%, n=5; MI: 10.6±2.3%, n=6 vs Epo 20.3±1.9%, n=8). These data suggest an activation of myogenic progenitors by Epo, despite the lack of apparent regeneration under the investigated conditions. In conclusion, we found that EpoR is expressed in a putative cardiomyogenic progenitor cell pool in the adult heart. Epo drives their proliferation in vitro and in vivo even upon acute cardiac injury. We are currently investigating the long-term consequences of the observed progenitor cell activation in models of chronic ischemic injury.

scholarly journals Successful Treatment of Bulla with Endobronchial Valves

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Erdoğan Çetinkaya ◽  
Mehmet Akif Özgül ◽  
Şule Gül ◽  
Hilal Boyacı ◽  
Ertan Cam ◽  
...  
Keyword(s):  
Lung Function ◽  
Treatment Options ◽  
Forced Expiratory Volume ◽  
Middle Lobe ◽  
Functional Improvement ◽  
X Ray ◽  
Chest X Ray ◽  
Right Middle Lobe ◽  
The Right ◽  
End Stage

Emphysematous bullae are a complication of end-stage COPD. Patients with large bullae and poor respiratory function have limited treatment options. Surgical resection is a recognized treatment, but functional improvement after bullectomy is not satisfactory in patients with forced expiratory volume in 1 s (FEV1) < 35% predicted. When this 59-year-old male end-stage COPD patient was assessed, he was cachectic and lung function tests showed a FEV1 of 0.56 L (19% predicted) and a RV of 7 L (314% predicted), while 6MWT was 315 m and MRC dyspnea score was 4. Chest X-ray revealed a massive bulla of 10 cm in diameter in the right middle lobe. A fibrobronchoscopy was performed under local anesthesia and 2 Zephyr 4.0 valves were placed in the right middle lobe. Chest X-ray and CT scan performed 36 days later showed the complete resolution of the bulla. Seven months later, the patient demonstrated an improvement in FEV1 (+30%) and a decrease in RV from 314 to 262% predicted. This case report shows that the Zephyr valves may be successfully used to treat a large bulla in the right middle lobe in a patient with diffuse emphysema and severely impaired lung function.

Abstract 1845: Adult Cardiac Progenitor Cells Promote Angiogenesis and Cardioprotection through Their Secreted Soluble Vcam-1

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Katsuhisa Matsuura ◽  
Atsushi Honda ◽  
Toshio Nagai ◽  
Noritoshi Fukushima ◽  
Tatsuya Shimizu ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cell Injury ◽  
Cell Sheet ◽  
Fold Increase ◽  
Neonatal Rat ◽  
Antibody Array ◽  
Cardiac Progenitor Cells ◽  
Protective Effects ◽  
Rat Cardiomyocytes ◽  
Promising Source

Although cardiac progenitor cells have been thought to be the promising source of cell therapy, the precise mechanisms of their paracrine action have not been fully elucidated. Since we observed that the transplantation of clonal expanded Sca-1 positive cardiac progenitor cells (cSca-1 cells) derived from adult murine heart by using cell sheet technique improved cardiac function of infarcted heart compared to adipose tissue derived mesenchymal cells (ATMC), we explored the secreted factors highly expressed in cSca-1 cells and identified that soluble VCAM-1 (sVCAM-1) was much abundant in cSca-1 cells compared to ATMC by using cytokine antibody array. cSca-1 cells-derived conditioned medium (CM) significantly enhanced endothelial migration and matrigel tube formation and these effects were abolished by knock down of VCAM-1 (Fold increase: control, 1.0; CM, 2.97 ± 0.21; siVCAM-1, 1.98 ± 0.09; siControl, 2.76 ± 0.05, p<0.01), suggesting that cSca-1 cells promote angiogenesis via their secreted sVCAM-1. We next examined whether sVCAM-1 conferred direct protective effects on cardiomyocytes. We exposed cardiomyocytes to 0.2 mM H 2 O 2 in the absence or presence of sVCAM-1 or CM and examined cardiomyocyte viability by MTT assay. The exposure of cardiomyocytes to H 2 O 2 significantly induced the cell injury. Interestingly when pretreated with sVCAM-1 or CM, the cell damages of cardiomyocytes by H 2 O 2 were significantly reduced. However when pretreated with anti-VLA4 antibody, a principal coreceptor of sVCAM-1, CM mediated cell protected effect was completely inhibited (Fold increase: control, 1.0; anti-VLA4, 0.89 ± 0.33; sVCAM-1, 1.69 ± 0.27; CM, 2.08 ± 0.28; CM+anti-VLA4, 1.07 ± 0.07, p<0.01), suggesting that a crucial role of the VLA4 in inducing survival of cardiomyocytes by CM. sVCAM-1 and CM induced phosphorylation of FAK, Akt, Erk and p38 MAPK in neonatal rat cardiomyocytes. When pretreated with wortmannin, SB203580 and PD98059, the cardioprotective effects of sVCAM-1 and CM significantly inhibited, suggesting that sVCAM-1 might protect cardiomyocytes from oxidative stress via integrated upregulation of Akt, Erk and p38MAPK. These findings suggest cardiac progenitor cells promote angiogenesis and cardioprotection through their secreted sVCAM-1.

Plasma Components which Interfere with Ristocetin-induced Platelet Aggregation

1975 ◽  
Vol 33 (03) ◽  
pp. 540-546 ◽  
Author(s):  
Robert F Baugh ◽  
James E Brown ◽  
Cecil Hougie
Keyword(s):  
Platelet Aggregation ◽  
Human Plasma ◽  
Plasma Proteins ◽  
Binding Protein ◽  
Plasma Heating ◽  
Protein S ◽  
Fold Increase ◽  
Normal Human Plasma ◽  
Preliminary Examination ◽  
Normal Human

SummaryNormal human plasma contains a component or components which interfere with ristocetin-induced platelet aggregation. Preliminary examination suggests a protein (or proteins) which binds ristocetin and competes more effectively for ristocetin than do the proteins involved in ristocetin-induced platelet aggregation. The presence of this protein in normal human plasma also prevents ristocetin-induced precipitation of plasma proteins at levels of ristocetin necessary to produce platelet aggregation (0.5–2.0 mg/ml). Serum contains an apparent two-fold increase of this component when compared with plasma. Heating serum at 56° for one hour results in an additional 2 to 4 fold increase. The presence of a ristocetin-binding protein in normal human plasma requires that this protein be saturated with ristocetin before ristocetin-induced platelet aggregation will occur. Variations in the ristocetin-binding protein(s) will cause apparent discrepancies in ristocetin-induced platelet aggregation in normal human plasmas.

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