scholarly journals Myocardial homing of mesenchymal stem cells following intrapericardial application and amplification by inflammation — an experimental pilot study

2017 ◽  
Vol 95 (9) ◽  
pp. 1064-1066 ◽  
Author(s):  
Nina Jung ◽  
Heinz Rupp ◽  
A. Rembert Koczulla ◽  
Claus F. Vogelmeier ◽  
Peter Alter
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Pilot Study ◽  
Cardiac Function ◽  
Cell Homing

Recent studies demonstrated potential effects of stem cells on cardiac function in heart failure. However, influences of the technique of application remained undetermined. In the present study, the pericardial sac was used as depot for fluorescent-labeled mesenchymal stem cells in rats. To evaluate influences of inflammation on cell homing, a sterile pericarditis was induced by talc. It is shown that intrapericardial stem cell application is sufficient to provide myocardial penetration. The extent of homing was amplified by inflammation in a talc-induced pericarditis.

SDF-1 Recruits Cardiac Stem Cell-Like Cells that Depolarize In Vivo

2007 ◽  
Vol 16 (9) ◽  
pp. 879-886 ◽  
Author(s):  
Samuel Unzek ◽  
Ming Zhang ◽  
Niladri Mal ◽  
William R. Mills ◽  
Kenneth R. Laurita ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cardiac Function ◽  
Connexin 43 ◽  
Cardiac Myocyte ◽  
Contractile Function ◽  
Vascular Density ◽  
Cardiac Myosin ◽  
Acute Mi

Prolongation or reestablishment of stem cell homing through the expression of SDF-1 in the myocardium has been shown to lead to homing of endothelial progenitor cells to the infarct zone with a subsequent increase in vascular density and cardiac function. While the increase in vascular density is important, there could clearly be other mechanisms involved. In a recent study we demonstrated that the infusion of mesenchymal stem cells (MSC) and MSC that were engineered to overexpress SDF-1 led to significant decreases in cardiac myocyte apoptosis and increases in vascular density and cardiac function compared to control. In that study there was no evidence of cardiac regeneration from either endogenous stem cells or the infused mesenchymal stem cells. In this study we performed further detailed immunohistochemistry on these tissues and demonstrate that the overexpression of SDF-1 in the newly infracted myocardium led to recruitment of small cardiac myosin-expressing cells that had proliferated within 2 weeks of acute MI. These cells did not differentiate into mature cardiac myocytes, at least by 5 weeks after acute MI. However, based on optical mapping studies, these cells appear capable of depolarizing. We observed greater optical action potential amplitude in the infarct border in those animals that received SDF-1 overexpressing MSC than observed in noninfarcted animals and those that received control MSC. Further immunohistochemistry revealed that these proliferated cardiac myosin-positive cells did not express connexin 43, but did express connexin 45. In summary, our study suggests that the prolongation of SDF-1 expression at the time of acute MI leads to the recruitment of endogenous cardiac myosin stem cells that may represent cardiac stem cells. These cells are capable of depolarizing and thus may contribute to increased contractile function even in the absence of maturation into a mature cardiac myocyte.

scholarly journals Mesenchymal stem cells engineered to overexpress stem cell factor improve cardiac function but have malignant potential

2008 ◽  
Vol 136 (5) ◽  
pp. 1388-1389 ◽  
Author(s):  
Shafie S. Fazel ◽  
Denis Angoulvant ◽  
Jagdish Butany ◽  
Richard D. Weisel ◽  
Ren-Ke Li
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cardiac Function ◽  
Stem Cell Factor ◽  
Malignant Potential

scholarly journals Mesenchymal stem cells from human amniotic membrane differentiate into cardiomyocytes and endothelial-like cells without improving cardiac function after surgical administration in rat model of chronic heart failure

2019 ◽  
Vol 11 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Fazel Gorjipour ◽  
Ladan Hosseini-Gohari ◽  
Alireza Alizadeh Ghavidel ◽  
Seyed Javad Hajimiresmaiel ◽  
Nasim Naderi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Troponin T ◽  
Left Ventricular ◽  
Border Zone ◽  
Vascular Endothelial ◽  
Tissue Fibrosis

Introduction: Human amnion-derived mesenchymal stem cells (hAMSCs) have been used in the treatment of acute myocardial infarction. In the current study, we investigated the efficacy of hAMSCs for the treatment of chronic model of myocardial ischemia and heart failure (HF) in rats. Methods: Male Wistar rats weighing between 250 to 350 g were randomized into three groups: sham, HF control and HF+hAMSCs. For HF induction, animals were anesthetized and underwent left anterior descending artery ligation. In HF+hAMSCs group, 2×106 cells were injected into the left ventricular muscle four weeks post ischemia in the border zone of the ischemic area. Cardiac function was studied using echocardiography. Masson’s trichrome staining was used for studying tissue fibrosis. Cells were transduced with green fluorescent protein (GFP) coding lentiviral vector. Immunohistochemistry was used for detecting GFP, vascular-endothelial growth factor (VEGF) and troponin T markers in the tissue sections. Results: Assessment of the cardiac function revealed no improvement in the myocardial function compared to the control HF group. Moreover, tissue fibrosis was similar in two groups. Immunohistochemical study revealed the homing of the injected hAMSCs to the myocardium. Cells were stained positive for VEGF and troponin T markers. Conclusion: injection of hAMSCs 4 weeks after ischemia does not improve cardiac function and cardiac muscle fibrosis, although the cells show markers of differentiation into vascular endothelial cells and cardiomyocytes. In sum, it appears that hAMSCs are effective in the early phases of myocardial ischemia and does not offer a significant advantage in patients with chronic HF.

scholarly journals Heart rate variability and cardiac function in heart failure rats treated with allogeneic mesenchymal stem cells (547.21)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Sharon Morais ◽  
Renata Lataro ◽  
Carlos Alberto Silva ◽  
Luciano Oliveira ◽  
Eduardo Carvalho ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function

Abstract 151: Cell-based Therapies for Heart Failure: Changes in Cytokine Expression From Mesenchymal Stem Cells and Induced Pluripotent Stem Cell Derived Cardiomyocytes

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Amitabh C Pandey ◽  
Jordan Lancaster ◽  
David Harris ◽  
Steven Goldman ◽  
Elizabeth Juneman
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factor ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Paracrine Signaling ◽  
Induced Pluripotent

Mesenchymal stem cells (MSCs) use paracrine signaling to modulate the cellular microenvironment via expression of cytokines, chemokines, and adhesion molecules to aid and promote endogenous repair. Induced pluripotent stem cell derived cardiomyocyte (iPSC-CMs) and mesenchymal stem cells (MSCs) together may play a synergistic role in changing the microenvironment milieu to allow for endogenous cellular repair through paracrine signaling. Cytokine expression is involved in the progression of heart failure (HF). Using a rat model of HF, cell based therapies with a fibroblast embedded patch only, iPSC-CM patch, and MSCs via tail vein (IV) or intracardiac injections (IC) to the left ventricle (LV) were administered, and RNA was subsequently isolated, and real-time polymerase chain reaction (PCR) was performed for analysis of gene expression. Evaluation of gene expression revealed significant increases in the expression of connexin 43 with iPSC-CMs (p<0.05). Expression of MMP9 was decreased with MSCs alone (p<0.05) but with the use of the patch with both cell types, its levels were significantly increased (p<0.05). Myosin heavy chain was seen to increase significantly with increasing cell numbers in iPSC-CM therapy (p<0.05). Markers of angiogenesis including vascular endothelial growth factor, angiopoietin, and insulin like growth factor were significantly increased with iPSC-CM patch therapy (p<0.05). Up-regulation of angiogenic cytokines and cardio-protective cytokines may help in slowing progression of HF. Interestingly, we also observed an increase in some markers, which were associated with HF. In conclusion, both iPSC-CM patch and MSCs altered signaling in the setting of HF, perhaps leading to improvement of at the cellular level. An iPSC-CM-based patch and MSCs as an adjuvant therapy may be able to play a role in the setting of HF as cellular therapeutic approach.

scholarly journals Heart failure therapy mediated by the trophic activities of bone marrow mesenchymal stem cells: a noninvasive therapeutic regimen

2009 ◽  
Vol 296 (6) ◽  
pp. H1888-H1897 ◽  
Author(s):  
Arsalan Shabbir ◽  
David Zisa ◽  
Gen Suzuki ◽  
Techung Lee
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Therapeutic Regimen ◽  
Subsequent Increase ◽  
Intramyocardial Injection ◽  
Trophic Effects ◽  
Marrow Mesenchymal Stem Cells

Heart failure carries a poor prognosis with few treatment options. While myocardial stem cell therapeutic trials have traditionally relied on intracoronary infusion or intramyocardial injection routes, these cell delivery methods are invasive and can introduce harmful scar tissue, arrhythmia, calcification, or microinfarction in the heart. Given that patients with heart failure are at an increased surgical risk, the development of a noninvasive stem cell therapeutic approach is logistically appealing. Taking advantage of the trophic effects of bone marrow mesenchymal stem cells (MSCs) and using a hamster heart failure model, the present study demonstrates a novel noninvasive therapeutic regimen via the direct delivery of MSCs into the skeletal muscle bed. Intramuscularly injected MSCs and MSC-conditioned medium each significantly improved ventricular function 1 mo after MSC administration. MSCs at 4 million cells/animal increased fractional shortening by ∼40%, enhanced capillary and myocyte nuclear density by ∼30% and ∼80%, attenuated apoptosis by ∼60%, and reduced fibrosis by ∼50%. Myocyte regeneration was evidenced by an approximately twofold increase in the expression of cell cycle markers (Ki67 and phosphohistone H3) and an ∼13% reduction in mean myocyte diameter. Increased circulating levels of hepatocyte growth factor (HGF), leukemia inhibitory factor, and macrophage colony-stimulating factor were associated with the mobilization of c-Kit-positive, CD31-positive, and CD133-positive progenitor cells and a subsequent increase in myocardial c-Kit-positive cells. Trophic effects of MSCs further activated the expression of HGF, IGF-II, and VEGF in the myocardium. The work highlights a cardiac repair mechanism mediated by trophic cross-talks among the injected MSCs, bone marrow, and heart that can be explored for noninvasive stem cell therapy.

scholarly journals Clinical observation of a patient with chronic heart failure after mesenchymal stem cell implantation in outpatient conditions

2021 ◽  
pp. 131-139
Author(s):  
O. L. Nikiforova ◽  
L. N. Prikhodko ◽  
P. N. Kovalchuk
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Clinical Practice ◽  
Chronic Heart Failure ◽  
Mesenchymal Stem Cell ◽  
Clinical Observation ◽  
Laboratory Studies ◽  
Cell Implantation

The article presents a case of a successful application of mesenchymal stem cells in clinical practice and provides an analysis of literature sources on this topic, clinical data, and results of laboratory studies.

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