Mesenchymal Progenitor Cells Differentiate into an Endothelial Phenotype, Enhance Vascular Density, and Improve Heart Function in a Rat Cellular Cardiomyoplasty Model

Davani, Siamak; Marandin, Aliette; Mersin, Nursen; Royer, Bernard; Kantélip, B.; Hervé, P.; Etievent, Joseph-Philippe; Kantelip, Jean-Pierre

doi:10.1161/01.cir.0000089186.09692.fa

Cited by 230 publications

(212 citation statements)

References 26 publications

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“…Consistently, previous studies have reported that stem cell therapyenhanced angiogenesis may play an essential role in improving LV function in the setting of ischemia-related organ dysfunction. 3,25,28,[30][31][32] Accordingly, our findings, in addition to reinforcing those of previous studies, 3,25,28,[30][31][32] could partially explain the notable improvement in endothelial function (ie, ET-1 level decreased in Supplemental Figure 3E, 3F) and heart function after BMDMSC transplantation.…”

Section: Discussionsupporting

confidence: 91%

“…BMDMSC transplantation improved heart function -role of paracrine/chemokine effects and generation of angiogenesis factors: A number of studies have previously shown that paracrine effects and enhanced production of chemokines 3,6,[28][29][30][31] and cytokines 32) played an important role in improving ischemia-related organ dysfunction. One important finding in the present study is the fact that, as compared with MI animals without treatment, the gene expressions of eNOS, VEGF, and IL-8/Gro, three indicators of paracrine/chemokine factors in both infarct and peri-infarct areas, were remarkably increased in MI animals after BMDMSC therapy.…”

Section: Discussionmentioning

confidence: 99%

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Prompt Bone Marrow-Derived Mesenchymal Stem Cell Therapy Enables Early Porcine Heart Function Recovery from Acute Myocardial Infarction

Fan

Leu²,

Sheu

et al. 2014

Int. Heart J.

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SummaryImpact of early bone marrow-derived mesenchymal stem cell (BMDMSC) implantation on left ventricular (LV) function after AMI was studied.Twelve mini-pigs were equally divided into placebo (AMI through left coronary artery ligation) and cell-treated groups [BMDMSCs (3.0 × 10 7 ) implanted into infarct area (IA)] with myocardium harvested by post-AMI day 90. Six healthy animals served as controls.On post-AMI day 90, magnetic resonance imaging showed a lower LV ejection fraction but higher LV dimensions in the placebo group (P < 0.003) that also had increased IAs but reduced wall thickness (P < 0.005). Pro-apoptotic gene expressions (Bax, caspase-3) and apoptotic nucleus number in IAs and peri-IAs were highest in the placebo group (P < 0.001). Inflammatory biomarker expressions (MMP-9, oxidized protein, CD40+ cells) were highest, whereas those of angiogenesis (VEGF, CD31+ cells, SDF-1α, CXCR4) and myocardium-preservation (connexin43, troponin-I, cytochrome-C) were lowest in the placebo group (P < 0.01).BMDMSC implantation preserved LV function and alleviated remodeling at post-AMI day 90. ( 6-9) Indeed, some studies have reported that SC therapy exhibited only temporary 5,8,9) or minimal 10) effectiveness, or was even ineffective [11][12][13][14][15][16] in improving global LV ejection fraction (LVEF) in patients after acute myocardial infarction (AMI). Further analysis of these clinical trials revealed that stem cell therapy was performed only several days after 5,8,9,[11][12][13] rather than immediately after AMI. Thus, interpretation of the results of these experimental and clinical investigations are difficult because of multiple variables, including the differences in experimental and trial design, cell type used, timing of cell delivery, and parameters for outcome assessment. [1][2][3][4][5][6][7][8][9][10][11][12][13]17) To date, although there is still no definite explanation to account for the discrepancy in findings in the literature, [1][2][3][4][5][6][7][8][9][10][11][12][13] it is rational to believe that two factors are crucial in the success of SC therapy in improving ischemia-related LV dysfunction based on the results of previous reports, 4,5,[7][8][9][10][11][12][13] in other words, a larger number of SCs to be implanted 5,11,18) and an early timing of implantation [19][20][21] in the ischemic zone after AMI. Although small animals are frequently utilized in AMI experimentation From the

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Prompt Bone Marrow-Derived Mesenchymal Stem Cell Therapy Enables Early Porcine Heart Function Recovery from Acute Myocardial Infarction

Fan

Leu²,

Sheu

et al. 2014

Int. Heart J.

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“…It has also been demonstrated that BMSCs can differentiate into cardiac cell components and develop into functional phenotypes of myocardial cells within the microenvironment of the heart. 4 -6 Human mesenchymal stem cells cocultured with myocytes express myosin heavy chain, ␤-actin, and troponin T. 7 BMSCs can not only differentiate into myocytes but also improve left ventricular performance 8 and cause a significant reduction of infarct size when injected into the infarcted hearts or border zones of rats or mice. 5,6,9 Moreover, BMSCs can be delivered into the coronary artery, because they are capable of targeted migration and differentiation into cardiomyocytes in the scar tissue to improve cardiac function.…”

mentioning

confidence: 99%

Differentiation of Bone Marrow Stromal Cells Into the Cardiac Phenotype Requires Intercellular Communication With Myocytes

et al. 2004

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Background-Bone marrow stromal cells (BMSCs) have the potential to differentiate into various cells and can transdifferentiate into myocytes if an appropriate cellular environment is provided. However, the molecular signals that underlie this process are not fully understood. In this study, we show that BMSC differentiation is dependent on communication with cells in their microenvironment. Methods and Results-BMSCs were isolated from green fluorescent protein (GFP)-transgenic mice and cocultured with myocytes in a ratio of 1:40. Myocytes were obtained from neonatal rat ventricles. The differentiation of BMSCs in coculture was confirmed by immunohistochemistry, electron microscopy, and reverse transcription-polymerase chain reaction. Before coculturing, the BMSCs were negative for ␣-actinin and exhibited a nucleus with many nucleoli. After 7-day coculture with myocytes, some BMSCs became ␣-actinin-positive and formed gap junctions with native myocytes. However, BMSCs separated from myocytes by a semipermeable membrane were still negative for ␣-actinin.

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“…Neste trabalho, Silva et al 38 observaram melhora de fração de ejeção no grupo tratado, sendo possível identificar, após 60 dias, diferenciação das células implantadas em células musculares lisas e endoteliais, mas não em cardiomiócitos. sugerem que a melhora, neste modelo de isquemia crônica, seria relacionada ao aumento da perfusão, secundária à angiogênese induzida pela terapia celular, sendo semelhantes a achados de estudos realizados em isquemia aguda em ratos 39 .…”

Section: Células Mesenquimais Da Medula óSseaunclassified

Terapia celular no tratamento da insuficiência cardíaca isquêmica

Fernandes¹,

Silva²

2007

Rev. Bras. Cardiol. Invasiva

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In this article the authors discuss the state of the art on cell therapy for ischemic heart failure. The principal cell types and their specific characteristics for the treatment of this pathology are presented. DESCRIPTORS:Tissue therapy. Myocardium. Myoblasts. Cell transplantation, methods. Heart failure, congestive. Myocardial ischemia. RESUMONeste artigo, os autores discutem o estado da arte da terapia celular no tratamento da insuficiência cardíaca isquêmica. São apresentados os principais tipos celulares disponíveis e suas particularidades no tratamento desta doença. A s recentes mudanças propostas pelo American College of Cardiology/American Heart Association (ACA/AHA), expostas nas diretrizes para diagnós-tico e tratamento de insuficiência cardíaca 1 , chamam a atenção da comunidade médica para a identificação precoce desta doença. De acordo com tais diretrizes, nova definição foi criada, incluindo pacientes assintomáticos, com ou sem lesão cardíaca estrutural manifesta (classe A e B, respectivamente), porém sob risco de desenvolvimento de insuficiência cardíaca. Apesar de não se desconsiderar a classificação universalmente aceita e utilizada na prática clínica proposta pela New York Heart Association (NYHA), tais mudanças expõem uma preocupação crescente com a identificação precoce dos pacientes em risco. O racional por traz desta estratégia baseia-se no fato de que, uma vez estabelecida, a injúria ventricular torna-se irreversível, fazendo portanto parecer algo tardio o diagnóstico da insuficiência cardíaca já sintomática. Atualmente, as opções terapêuticas disponíveis são voltadas para o controle da hiperativação do sistema neurohumoral, tratamento da etiologia, quando possível, e prevenção da morte súbita (cardioversores-desfibriladores implantáveis), quando indicado. DESCRITORES:Recentemente, a capacidade reparativa cardíaca foi demonstrada em estudos pré-clínicos 2-4 . A demonstração de células de origem extracardíaca, identificadas pela presença de cromossomo Y em pacientes do sexo masculino transplantados a partir de doadoras do sexo feminino, nos leva a questionar o paradigma vigente, o qual se baseia na incapacidade regenerativa do coração e na conseqüente substituição por tecido fibrótico após exposição a injúria miocárdica e morte celular 4 . Talvez, mais adequado seja pensarmos que a higidez do coração, bem como de todo sistema, é resultante de um equilíbrio entre exposição a fatores agressores e capacidade reparativa. Portanto, o dano estrutural resulta do desequilíbrio de tal homeostasia, seja por uma maior exposição à agressão crônica ou aguda (insultos isquêmicos agudos ou crônicos cumulativos), seja por uma redução da reserva reparativa (idade, diabetes) 5-7 .Entretanto, é inegável a ineficácia de eventuais mecanismos naturais de reparo em condições de agressão extrema, como no caso de infarto agudo do miocárdio e, posteriormente à injúria estabelecida, no processo de remodelamento ventricular. Após a perda de cardiomiócitos, seja por insulto isquêmico e resultante necrose, seja por aum...

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Mesenchymal Progenitor Cells Differentiate into an Endothelial Phenotype, Enhance Vascular Density, and Improve Heart Function in a Rat Cellular Cardiomyoplasty Model

Cited by 230 publications

References 26 publications

Prompt Bone Marrow-Derived Mesenchymal Stem Cell Therapy Enables Early Porcine Heart Function Recovery from Acute Myocardial Infarction

Prompt Bone Marrow-Derived Mesenchymal Stem Cell Therapy Enables Early Porcine Heart Function Recovery from Acute Myocardial Infarction

Differentiation of Bone Marrow Stromal Cells Into the Cardiac Phenotype Requires Intercellular Communication With Myocytes

Terapia celular no tratamento da insuficiência cardíaca isquêmica

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