Endothelial Cells Promote Cardiac Myocyte Survival and Spatial Reorganization

Narmoneva, Daria A.; Vukmirovic, Rada; Davis, Michael; Kamm, Roger D.; Lee, Richard T.

doi:10.1161/01.cir.0000140667.37070.07

Cited by 329 publications

(281 citation statements)

References 41 publications

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“…These data are consistent with the fact that we have recently demonstrated that the presence of endothelial cells improves survival and organization of cardiomyocytes in vitro. 13 The data in the present study suggest that endothelial cell presence within the peptide microenvironments may be important in cell survival and recruitment. Furthermore, we saw development of functional ␣-smooth muscle actin- positive vessels within the myocardium, including some with red blood cells within, suggesting that angiogenesis also occurs within the microenvironment with a specific time course and that new vessels are capable of connection to the host vasculature.…”

Section: Discussionmentioning

confidence: 50%

“…13 To determine whether microenvironments can be established with injected peptides in vivo, the LV free wall of adult male C57BL6 mice was injected with 1% RAD16-II immediately after suspension of peptides at pHϭ7.0 and osmolarity of 295 mOsm. The hearts were later excised, fixed in 4% (wt/vol) paraformaldehyde, and embedded in paraffin.…”

Section: Detection Of Injected Peptide Gel and Cell Infiltrationmentioning

confidence: 99%

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Injectable Self-Assembling Peptide Nanofibers Create Intramyocardial Microenvironments for Endothelial Cells

et al. 2005

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Background-Promoting survival of transplanted cells or endogenous precursors is an important goal. We hypothesized that a novel approach to promote vascularization would be to create injectable microenvironments within the myocardium that recruit endothelial cells and promote their survival and organization. Methods and Results-In this study we demonstrate that self-assembling peptides can be injected and that the resulting nanofiber microenvironments are readily detectable within the myocardium. Furthermore, the self-assembling peptide nanofiber microenvironments recruit progenitor cells that express endothelial markers, as determined by staining with isolectin and for the endothelial-specific protein platelet-endothelial cell adhesion molecule-1. Vascular smooth muscle cells are recruited to the microenvironment and appear to form functional vascular structures. After the endothelial cell population, cells that express ␣-sarcomeric actin and the transcription factor Nkx2.5 infiltrate the peptide microenvironment. When exogenous donor green fluorescent protein-positive neonatal cardiomyocytes were injected with the self-assembling peptides, transplanted cardiomyocytes in the peptide microenvironment survived and also augmented endogenous cell recruitment. Conclusions-These experiments demonstrate that self-assembling peptides can create nanofiber microenvironments in the myocardium and that these microenvironments promote vascular cell recruitment. Because these peptide nanofibers may be modified in a variety of ways, this approach may enable injectable tissue regeneration strategies.

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Section: Discussionmentioning

confidence: 50%

Section: Detection Of Injected Peptide Gel and Cell Infiltrationmentioning

confidence: 99%

Injectable Self-Assembling Peptide Nanofibers Create Intramyocardial Microenvironments for Endothelial Cells

et al. 2005

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“…RADA16 spontaneously assembles in the presence of monovalent salt or under physiological conditions as a result of both the ionic side chain interactions and the conventional b-sheet propensity of the backbone, ultimately forming a macroscopic hydrogel known to facilitate cell culture. 14,[16][17][18] Cell attachment and neurite outgrowth were enhanced when neural cells were cultured on this hydrogel. Moreover, cells may be embedded in RADA16 peptide hydrogels, providing a 3-D environment for the cells to grow.…”

Section: Introductionmentioning

confidence: 98%

Hydrogel scaffolds composed of genetically synthesized self-assembling peptides for three-dimensional cell culture

Mie

Oomuro

Kobatake

2012

Polym J

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Peptides were genetically produced that were composed of two or three repeats of the self-assembling peptide RADA16 (RADARADARADARADA), and referred to as RADA16 Â 2 and RADA16 Â 3, respectively. These peptides were expressed as fusion proteins that retained the activity of the fusion partner protein. The expressed peptides exhibited both fibril formation and the ability to support cell adhesive activity. Moreover, hydrogels formed by the peptides via the addition of a medium provided a three-dimensional environment for cell proliferation. Polymer Journal (2013) 45, 504-508; doi:10.1038/pj.2012.216; published online 12 December 2012Keywords: 3-D cell culture; genetically synthesis; hydrogel; self-assembling peptide INTRODUCTIONThe development of biomaterials that support cellular functions, such as cell adhesion, growth and differentiation, is important for tissue engineering. 1 In an effort to create such novel biomaterials, artificial extracellular matrices (ECMs) have been developed by various groups. [2][3][4][5] Artificial ECM proteins have been designed and genetically synthesized in our laboratory. 6-10 Our strategy for the design of artificial ECM proteins relies on the combination of structural peptides and active functional peptides that control cellular functions. One of the ECM proteins previously constructed in our lab, named ERE, is composed of 12 repeats of the elastin-derived APGVGV peptide motif as the stable structural peptide, with the cell adhesive RGD peptide motif as the active functional peptide. 6,7 ERE can be immobilized on a hydrophobic surface via the hydrophobic APGVGV peptide motif and exhibits cell adhesive activities as a result of the RGD peptide. Multi-functional ECM proteins have also been constructed based on the ERE protein. EREI, which consists of ERE fused with the IKVAV peptide, not only exhibits cell adhesive activity but also promotes angiogenesis and neural differentiation as a result of the combination of IKVAV and RGD. [8][9][10][11][12] In our genetic engineering-based designs, multi-functional ECMs composed not only of peptide motifs but also of growth factors were constructed. Epidermal growth factor fused to the ERE protein was found to exhibit cell growth activity via the epidermal growth factor moiety. 7 Our genetically designed ECM proteins based on ERE demonstrated applicability as biomaterials. 6-10 However, covalent cross-linking is required to form a hydrogel structure in order to

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“…O implante de células-tronco em estruturas biodegradáveis demonstrou ser um método plausível e associado a resultados positivos in vitro 38 . Alternativas envolvendo a combinação de cardiomioplastia celular com terapia genética também vêm sendo testadas com sucesso em modelos experimentais in vivo 39 .…”

Section: Perspectivas Futurasunclassified

Terapia celular no tratamento do infarto agudo do miocárdio

Angeli¹,

Oliveira²

2007

Rev. Bras. Cardiol. Invasiva

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SUMMARY Cell Therapy in the Treatment of Acute Myocardial InfarctionIn this article, the authors discuss the concepts and available current evidence about cell therapy in the treatment of patients with acute myocardial infarction. The cell types that are potential candidates for clinical use are detailed as are the administration routes and future perspectives. DESCRIPTORS:Tissue therapy. Myocardial infarction, therapy. Stem cell transplantation. RESUMONeste artigo, os autores abordam os conceitos e evidências atualmente disponíveis sobre a terapia celular no tratamento de pacientes pós-infarto agudo do miocárdio. Os tipos celulares potencialmente candidatos ao uso clínico são enfatizados, considerando-se as vias de administração e as perspectivas futuras.DESCRITORES: Terapia tissular. Infarto do miocárdio, terapia. Transplante de células-tronco. Nos últimos anos, a medicina cardiovascular passou por uma das suas mais extraordinárias revoluções: a explosão de estudos pré-clínicos e clínicos suportando a hipótese de que o tecido cardíaco lesado poderia ser reparado com a administração de células-tronco e da conseqüente formação de novos vasos e miócitos. Apesar da incerteza em relação ao mecanismo pelo qual a terapia celular melhora a função cardíaca e regenera sua anatomia, a tradução dos achados obtidos em laboratório para o cenário clínico vem ocorrendo em ritmo cada vez mais acelerado 2 . Um número expressivo de pequenos estudos, na sua maioria não randomizados, reportaram a melhora da perfusão e função cardíaca após terapia com diferentes tipos celulares em pacientes com IAM 2 . Apenas mais recentemente, estudos randomizados envolvendo um maior número de pacientes começaram a ter seus resultados disponibilizados na literatura. A heterogeneidade dos resultados nos estudos publicados até o presente momento ampliou os questionamentos sobre a efetividade e metodologia utilizada na geração destes dados 3-5 . Artigo de RevisãoIndependente das evidências atualmente disponí-veis, é fundamental que se enfatize que muitas ainda são as perguntas a serem respondidas antes que a terapia celular possa ser plenamente compreendida e, só então, aceita ou descartada como opção terapêu-tica. Pontos relevantes a serem abordados, dentro deste cenário, correlacionam-se com a identificação da célula ou produto ideal, sua posologia, a melhor via e o momento temporal para sua administração.Nesta breve revisão, abordaremos os conceitos e evidências atualmente disponíveis sobre a terapia celular no tratamento de pacientes pós-infarto agudo do miocárdio. Por motivos metodológicos, optamos por uma abordagem baseada nos tipos celulares potencialmente candidatos ao uso clínico. Terapia celular no IAM em 2007: até onde chegamosCélulas-tronco podem ser definidas como células que possuem capacidade clonogênica e de auto-renovação e, ainda, que podem diferenciar-se em múlti-

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Endothelial Cells Promote Cardiac Myocyte Survival and Spatial Reorganization

Cited by 329 publications

References 41 publications

Injectable Self-Assembling Peptide Nanofibers Create Intramyocardial Microenvironments for Endothelial Cells

Injectable Self-Assembling Peptide Nanofibers Create Intramyocardial Microenvironments for Endothelial Cells

Hydrogel scaffolds composed of genetically synthesized self-assembling peptides for three-dimensional cell culture

Terapia celular no tratamento do infarto agudo do miocárdio

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