Stem Cell Treatment Heart Disease

Stem Cells and Heart Disease

Stem Cell Treatments for Heart Disease is an Option

Cardiovascular diseases remain the biggest cause of deaths worldwide, though over the last two decades, cardiovascular mortality rates have declined in many high-income countries but have increased at an astonishingly fast rate in low- and middle-income countries. The percentage of premature deaths from cardiovascular disease range from 4% in high-income countries to 42% in low-income countries. More than 17 million people died from cardiovascular diseases in 2008. Each year, heart disease kills more Americans than cancer. In recent years, cardiovascular risk in women has been increasing and has killed more women than breast cancer.

Measures to prevent cardiovascular disease may include:

  • Keeping unapposed simple carbohydrates under control, no matter what type: fruit, bread, dairy, etc.
  • decrease emotional stress, or how you react to the environment (traffic, work, deadlines, lifestyle, etc.)
  • a low fat high fiber diet including whole grains and plenty of fresh fruit and vegetables (at least five portions a day)
  • a diet high in complex vegetables and colorful fruit
  • tobacco cessation;
  • limit alcohol consumption;
  • lower blood pressures if elevated through diet and exercise;
  • decrease body fat (BMI);
  • increase daily activity to 30 minutes of any kind of exercise per day at least five times per week

A fairly recent emphasis is on the link between low-grade inflammation that hallmarks atherosclerosis and its possible interventions. C-reactive protein (CRP) is a common inflammatory marker that has been found to be present in increased levels in patients at risk for cardiovascular disease. Also osteoprotegerin which is involved with regulation of a key inflammatory transcription factor called NF-κB has been found to be a risk factor of cardiovascular disease and mortality. Studies have shown that Stem Cells have shown the ability to reduce inflammation.


Stem Cell Treatments for Heart Disease is an Option

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Related Articles Injection of basic fibroblast growth factor together with adipose-derived stem cell transplantation: improved cardiac remodeling and function in myocardial infarction. Clin Exp Med. 2016 Nov;16(4):539-550 Authors: Wang B, Ma X, Zhao L, Zhou X, Ma Y, Sun H, Yang Y, Chen B Abstract Recent findings suggest that cell and gene transplantation in the infarcted myocardium may improve heart function. The aim of the study was to investigate the mechanism involved in improving heart function following the co-injection of adipose-derived stem cells (ADSCs) and basic fibroblast growth factor (bFGF) in a rat model of myocardial infarction. In this study, ADSCs were isolated from subcutaneous adipose tissues. The ADSCs were induced to differentiate into adipocytes, osteoblasts and cardiac myocytes in vitro. bFGF was co-injected with the ADSCs into the left ventricular wall in a rat myocardial infarction model. The structural and functional outcomes resulting from this transplantation were determined through detailed histological analysis and echocardiography. The graft size was significantly larger in the bFGF + ADSC group than in the PBS + ADSC group and PBS + bFGF group 4 weeks after injection (p < 0.05). The ADSCs were able to differentiate into cardiomyocytes, endothelial cells and vascular smooth muscle cells in vivo. There was a significant improvement in arteriole density within the infarcted area in the bFGF + ADSC group compared with the PBS + ADSC group and the PBS + bFGF group 4 weeks after transplantation (p < 0.05). The results of Western blot analysis showed that all of the treatments significantly reduced MMP2 and MMP9 protein levels compared with the PBS control group (p < 0.05) and that the levels of these proteins displayed the largest decrease in the bFGF + ADSC group (p < 0.05). In addition, the results of a quantitative analysis revealed that the proportion of fibrotic areas was significantly lower in the PBS + ADSC and bFGF + ADSC groups compared with the PBS-only group and PBS + bFGF group (p < 0.05). The combined application of bFGF and ADSC transplantation may significantly increase the number of arterioles, reduce the infarcted size, attenuate ventricular remodeling and improve cardiac function. This ADSC + bFGF treatment strategy (or a variation thereof) may prove to be broadly applicable to other candidate cell preparations used in regenerative medicine. PMID: 26349680 [PubMed - indexed for MEDLINE]
Related Articles Preconditioning of mesenchymal stem cells with 2,4-dinitrophenol improves cardiac function in infarcted rats. Life Sci. 2016 Oct 01;162:60-9 Authors: Khan I, Ali A, Akhter MA, Naeem N, Chotani MA, Mustafa T, Salim A Abstract AIMS: The aim of this study is to determine if preconditioning of bone marrow derived mesenchymal stem cells (MSCs) with 2,4-dinitrophenol (DNP) improves survival of transplanted stem cells in a rat model of myocardial infarction (MI), and to asses if this strategy has measurable impact on cardiac function. MAIN METHODS: MSCs were preconditioned with DNP. In vitro cell adhesion assay and qRT-PCR were performed to analyze the expression of genes involved in cardiomyogenesis, cell adhesion and angiogenesis. MI was produced by occlusion of left anterior descending coronary artery. One million cells were transplanted by intramyocardial injection into the infarcted myocardium. Echocardiography was performed after two and four weeks of cellular transplantation. Hearts were harvested after four weeks and processed for histological analysis. KEY FINDINGS: DNP treated MSCs adhered to the surface more (p<0.001) as compared to the normal MSCs. Gene expression levels were significantly upregulated in case of DNP treatment. The number of viable MSCs was more (p<0.001) in animals that received DNP treated MSCs, leading to significant improvement in cardiac function. Histological analysis revealed significant reduction in scar formation (p<0.001), maintenance of left ventricular wall thickness (p<0.001), and increased angiogenesis (p<0.01). SIGNIFICANCE: The study evidenced for the first time that MSCs preconditioned with DNP improved cardiac function after transplantation. This can be attributed to improved survival, homing, adhesion, and cardiomyogenic and angiogenic differentiation of DNP treated MSCs in vivo. PMID: 27543341 [PubMed - indexed for MEDLINE]
Related Articles Differential response of human cardiac stem cells and bone marrow mesenchymal stem cells to hypoxia-reoxygenation injury. Mol Cell Biochem. 2017 Jan;425(1-2):139-153 Authors: RajendranNair DS, Karunakaran J, Nair RR Abstract Cardiosphere-derived cells (CDCs) and bone marrow mesenchymal stem cells (MSCs) are popularly used in stem cell therapy for myocardial regeneration. The cell type that survives and maintains stem cell characteristics in the adverse microenvironment following ischemia-reperfusion injury is presumed to be ideal for transplantation. The study was therefore aimed at identifying the cell type with relatively greater resistance to ischemia-reperfusion injury. CDCs were isolated from the right atrial appendage and MSCs from bone marrow of patients who underwent coronary artery bypass graft surgery. Ischemia-reperfusion injury was simulated in vitro by subjecting the cells to hypoxia (0.5% O2) followed by reintroduction of oxygen (HR injury). Greater resistance of CDCs to HR injury was apparent from the decreased expression of senescence markers and lower proportion of apoptotic cells (one-sixth of that in MSCs). HR injury retarded cell cycle progression in MSCs. Consequent to HR injury, cell migration and secretion of stromal-derived growth factor were stimulated, significantly in CDCs. The differentiation to myocyte lineage and angiogenesis assessed by tube formation ability was better for CDCs. Release of vascular endothelial growth factor was relatively more in CDCs and was further stimulated by HR injury. Differentiation to osteogenic and angiogenic lineage was stimulated by HR injury in MSCs. Compared to MSCs, CDCs appear to be the cell of choice for promoting myocardial regeneration by virtue of its survival capacity in the event of ischemic insult along with higher proliferation rate, migration efficiency, release of growth factors with paracrine effects and differentiation to cardiac lineage. PMID: 27844250 [PubMed - indexed for MEDLINE]
Related Articles Cell Therapies in Cardiomyopathy: Current Status of Clinical Trials. Anal Cell Pathol (Amst). 2017;2017:9404057 Authors: Hao M, Wang R, Wang W Abstract Because the human heart has limited potential for regeneration, the loss of cardiomyocytes during cardiac myopathy and ischaemic injury can result in heart failure and death. Stem cell therapy has emerged as a promising strategy for the treatment of dead myocardium, directly or indirectly, and seems to offer functional benefits to patients. The ideal candidate donor cell for myocardial reconstitution is a stem-like cell that can be easily obtained, has a robust proliferation capacity and a low risk of tumour formation and immune rejection, differentiates into functionally normal cardiomyocytes, and is suitable for minimally invasive clinical transplantation. The ultimate goal of cardiac repair is to regenerate functionally viable myocardium after myocardial infarction (MI) to prevent or heal heart failure. This review provides a comprehensive overview of treatment with stem-like cells in preclinical and clinical studies to assess the feasibility and efficacy of this novel therapeutic strategy in ischaemic cardiomyopathy. PMID: 28194324 [PubMed - indexed for MEDLINE]
Related Articles A comparison of the pro-angiogenic potential of human induced pluripotent stem cell derived endothelial cells and induced endothelial cells in a murine model of peripheral arterial disease. Int J Cardiol. 2017 Jan 31;: Authors: Clayton ZE, Yuen GS, Sadeghipour S, Hywood JD, Wong JW, Huang NF, Ng MK, Cooke JP, Patel S Abstract BACKGROUND: Endothelial cells derived from human induced pluripotent stem cells (iPSC-ECs) promote angiogenesis, and more recently induced endothelial cells (iECs) have been generated via fibroblast trans-differentiation. These cell types have potential as treatments for peripheral arterial disease (PAD). However, it is unknown whether different reprogramming methods produce cells that are equivalent in terms of their pro-angiogenic capabilities. OBJECTIVES: We aimed to directly compare iPSC-ECs and iECs in an animal model of PAD, in order to identify which cell type, if any, displays superior therapeutic potential. METHODS: IPSC-ECs and iECs were generated from human fibroblasts, and transduced with a reporter construct encoding GFP and firefly luciferase for bioluminescence imaging (BLI). Endothelial phenotype was confirmed using in vitro assays. NOD-SCID mice underwent hindlimb ischaemia surgery and received an intramuscular injection of either 1×10(6) iPSC-ECs, 1×10(6) iECs or control vehicle only. Perfusion recovery was measured by laser Doppler. Hindlimb muscle samples were taken for histological analyses. RESULTS: Perfusion recovery was enhanced in iPSC-EC treated mice on day 14 (Control vs. iPSC-EC; 0.35±0.04 vs. 0.54±0.08, p<0.05) and in iEC treated mice on days 7 (Control vs. iEC; 0.23±0.02 vs. 0.44±0.06, p<0.05), 10 (0.31±0.04 vs. 0.64±0.07, p<0.001) and 14 (0.35±0.04 vs. 0.68±0.07, p<0.001) post-treatment. IEC-treated mice also had greater capillary density in the ischaemic gastrocnemius muscle (Control vs. iEC; 125±10 vs. 179±11 capillaries/image; p<0.05). BLI detected iPSC-EC and iEC presence in vivo for two weeks post-treatment. CONCLUSIONS: IPSC-ECs and iECs exhibit similar, but not identical, endothelial functionality and both cell types enhance perfusion recovery after hindlimb ischaemia. PMID: 28209385 [PubMed - as supplied by publisher]
Related Articles Burden of musculoskeletal disorders in the Eastern Mediterranean Region, 1990-2013: findings from the Global Burden of Disease Study 2013. Ann Rheum Dis. 2017 Feb 16;: Authors: Moradi-Lakeh M, Forouzanfar MH, Vollset SE, El Bcheraoui C, Daoud F, Afshin A, Charara R, Khalil I, Higashi H, Abd El Razek MM, Kiadaliri AA, Alam K, Akseer N, Al-Hamad N, Ali R, AlMazroa MA, Alomari MA, Al-Rabeeah AA, Alsharif U, Altirkawi KA, Atique S, Badawi A, Barrero LH, Basulaiman M, Bazargan-Hejazi S, Bedi N, Bensenor IM, Buchbinder R, Danawi H, Dharmaratne SD, Zannad F, Farvid MS, Fereshtehnejad SM, Farzadfar F, Fischer F, Gupta R, Hamadeh RR, Hamidi S, Horino M, Hoy DG, Hsairi M, Husseini A, Javanbakht M, Jonas JB, Kasaeian A, Khan EA, Khubchandani J, Knudsen AK, Kopec JA, Lunevicius R, Abd El Razek HM, Majeed A, Malekzadeh R, Mate K, Mehari A, Meltzer M, Memish ZA, Mirarefin M, Mohammed S, Naheed A, Obermeyer CM, Oh IH, Park EK, Peprah EK, Pourmalek F, Qorbani M, Rafay A, Rahimi-Movaghar V, Shiri R, Rahman SU, Rai RK, Rana SM, Sepanlou SG, Shaikh MA, Shiue I, Sibai AM, Silva DA, Singh JA, Skogen JC, Terkawi AS, Ukwaja KN, Westerman R, Yonemoto N, Yoon SJ, Younis MZ, Zaidi Z, Zaki ME, Lim SS, Wang H, Vos T, Naghavi M, Lopez AD, Murray CJ, Mokdad AH Abstract OBJECTIVES: We used findings from the Global Burden of Disease Study 2013 to report the burden of musculoskeletal disorders in the Eastern Mediterranean Region (EMR). METHODS: The burden of musculoskeletal disorders was calculated for the EMR's 22 countries between 1990 and 2013. A systematic analysis was performed on mortality and morbidity data to estimate prevalence, death, years of live lost, years lived with disability and disability-adjusted life years (DALYs). RESULTS: For musculoskeletal disorders, the crude DALYs rate per 100 000 increased from 1297.1 (95% uncertainty interval (UI) 924.3-1703.4) in 1990 to 1606.0 (95% UI 1141.2-2130.4) in 2013. During 1990-2013, the total DALYs of musculoskeletal disorders increased by 105.2% in the EMR compared with a 58.0% increase in the rest of the world. The burden of musculoskeletal disorders as a proportion of total DALYs increased from 2.4% (95% UI 1.7-3.0) in 1990 to 4.7% (95% UI 3.6-5.8) in 2013. The range of point prevalence (per 1000) among the EMR countries was 28.2-136.0 for low back pain, 27.3-49.7 for neck pain, 9.7-37.3 for osteoarthritis (OA), 0.6-2.2 for rheumatoid arthritis and 0.1-0.8 for gout. Low back pain and neck pain had the highest burden in EMR countries. CONCLUSIONS: This study shows a high burden of musculoskeletal disorders, with a faster increase in EMR compared with the rest of the world. The reasons for this faster increase need to be explored. Our findings call for incorporating prevention and control programmes that should include improving health data, addressing risk factors, providing evidence-based care and community programmes to increase awareness. PMID: 28209629 [PubMed - as supplied by publisher]
Related Articles Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN Patients with Intermittent Claudication Injected with ALDH Bright Cells (PACE) Trial. Circulation. 2017 Feb 16;: Authors: Perin EC, Murphy MP, March KL, Bolli R, Loughran J, Yang PC, Leeper NJ, Dalman RL, Alexander JQ, Henry TD, Traverse JH, Pepine CJ, Anderson RD, Berceli S, Willerson JT, Muthupillai R, Gahremanpour AA, Raveendran G, Velazquez OC, Hare JM, Schulman IH, Kasi VS, Hiatt WR, Ambale-Venkatesh B, Lima JA, Taylor DA, Resende MM, Gee AP, Durett AG, Bloom J, Richman S, G'Sell P, Williams S, Khan F, Ross EG, Santoso MR, Goldman J, Leach D, Handberg E, Cheong BY, Piece NA, DiFede D, Bruhn-Ding B, Caldwell E, Bettencourt J, Lai D, Piller LB, Simpson LM, Cohen M, Sayre SL, Vojvodic RW, Moyé L, Ebert RF, Simari RD, Hirsch AT, Cardiovascular Cell Therapy Research Network (CCTRN) Abstract Background -Atherosclerotic peripheral artery disease (PAD) affects 8-12% of Americans over 65 and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE is an NHLBI-sponsored, randomized, double-blind, placebo-controlled phase 2, exploratory clinical trial designed to assess safety and efficacy of autologous bone marrow-derived aldehyde dehydrogenase bright (ALDHbr) cells in PAD patients and to explore associated claudication physiologic mechanisms. Methods -All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by ten injections into the thigh and calf of the index leg. The co-primary endpoints were: change from baseline to six months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging (MRI); as well as safety. Results -A total of 82 patients with claudication and infra-inguinal PAD were randomized at nine sites, of which 78 had analyzable data (57 male, 21 female; mean age 66±9 years). The mean differences in the change over six months between study groups for PWT (mean ± standard error of the mean [SEM]) (0.9±0.8 minutes; 95% CI -0.6 to 2.5; p=0.238), collateral count (0.9±0.6 arteries; 95% CI -0.2 to 2.1; p=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/sec; 95% CI -0.8 to 0.8; p=0.978), and capillary perfusion (-0.2±0.6%; 95% CI -1.3 to 0.9; p=0.752) were not significant. Additionally, there were no significant differences for the secondary endpoints, including quality of life measures. There were no adverse safety outcomes. Correlative relationships between MRI measures and PWT were not significant. A post-hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI 0.1 to 2.9; p=0.047) in participants with completely occluded femoral arteries. Conclusions -ALDHbr cell administration did not improve PWT or MR outcomes, and the changes in PWT were not associated with the anatomic or physiologic MRI endpoints. Future PAD cell therapy investigational trial design may be informed by new anatomic and perfusion insights. Clinical Trial Registration Unique Identifier: NCT01774097. PMID: 28209728 [PubMed - as supplied by publisher]

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