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Reprogramming for cardiac regeneration.

Raynaud CM, Ahmad FS, Allouba M, Abou-Saleh H, Lui KO, Yacoub M - Glob Cardiol Sci Pract (2014)

Bottom Line: Treatment of cardiovascular diseases remains challenging considering the limited regeneration capacity of the heart muscle.Developments of reprogramming strategies to create in vitro and in vivo cardiomyocytes have been the focus point of a considerable amount of research in the past decades.The choice of cells to employ, the state-of-the-art methods for different reprogramming strategies, and their promises and future challenges before clinical entry, are all discussed here.

View Article: PubMed Central - PubMed

Affiliation: Qatar Cardiovascular Research Center, Qatar Foundation-Education City, Doha, Qatar.

ABSTRACT
Treatment of cardiovascular diseases remains challenging considering the limited regeneration capacity of the heart muscle. Developments of reprogramming strategies to create in vitro and in vivo cardiomyocytes have been the focus point of a considerable amount of research in the past decades. The choice of cells to employ, the state-of-the-art methods for different reprogramming strategies, and their promises and future challenges before clinical entry, are all discussed here.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of heart repair strategies using reprogramming technologies Two strategies to repair post myocardial infarction are envisioned using in vitro reprogramming techniques starting from skin fibroblast. First fibroblasts are reprogrammed into iPSCs before being differentiated into CMs using small molecules or cytokines. The second approach consists of a direct reprogramming of the skin fibroblast into iCMs. In both cases, the CMs produced in vitro have to be injected into the patient. When considering in situ reprogramming, the transcription factors (carried by viruses) are directly delivered to the patient and TFs will be expressed in cardiac fibroblasts, reprogramming them directly into iCMs. OKSM factors: Oct4, Sox2, Klf4, c-Myc.
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fig7: Schematic representation of heart repair strategies using reprogramming technologies Two strategies to repair post myocardial infarction are envisioned using in vitro reprogramming techniques starting from skin fibroblast. First fibroblasts are reprogrammed into iPSCs before being differentiated into CMs using small molecules or cytokines. The second approach consists of a direct reprogramming of the skin fibroblast into iCMs. In both cases, the CMs produced in vitro have to be injected into the patient. When considering in situ reprogramming, the transcription factors (carried by viruses) are directly delivered to the patient and TFs will be expressed in cardiac fibroblasts, reprogramming them directly into iCMs. OKSM factors: Oct4, Sox2, Klf4, c-Myc.

Mentions: The in vitro demonstration of direct fibroblast reprogramming previously discussed was performed on embryonic, neonatal, adult tail-tip, skin and cardiac fibroblasts.5,141,142 Fibroblasts have long been considered as of uniform cell type across different tissues.150,151 Morphologically they are flat, spindle-shaped cells with multiple processes emanating from the main cell body. They can be defined as mesenchymal cells producing extracellular matrix (ECM) components like collagens and fibronectin.152 This simple morphological definition highlighted a mistaken identity with mesenchymal stromal/stem cells (MSCs).153 This view has now been challenged by the demonstration of phenotypic heterogeneity of fibroblast from different tissues in different conditions.151 This heterogeneity poses an active area of investigation for direct reprogramming methods to focus on the most appropriate fibroblasts. But which fibroblast populations are the most appropriate to focus on? To answer this question, we might first need to address the question of the different strategies that can be foreseen using this direct reprogramming technique. Indeed, two types of therapy (summarized in Figure 7) can be envisioned using direct reprogramming.


Reprogramming for cardiac regeneration.

Raynaud CM, Ahmad FS, Allouba M, Abou-Saleh H, Lui KO, Yacoub M - Glob Cardiol Sci Pract (2014)

Schematic representation of heart repair strategies using reprogramming technologies Two strategies to repair post myocardial infarction are envisioned using in vitro reprogramming techniques starting from skin fibroblast. First fibroblasts are reprogrammed into iPSCs before being differentiated into CMs using small molecules or cytokines. The second approach consists of a direct reprogramming of the skin fibroblast into iCMs. In both cases, the CMs produced in vitro have to be injected into the patient. When considering in situ reprogramming, the transcription factors (carried by viruses) are directly delivered to the patient and TFs will be expressed in cardiac fibroblasts, reprogramming them directly into iCMs. OKSM factors: Oct4, Sox2, Klf4, c-Myc.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352683&req=5

fig7: Schematic representation of heart repair strategies using reprogramming technologies Two strategies to repair post myocardial infarction are envisioned using in vitro reprogramming techniques starting from skin fibroblast. First fibroblasts are reprogrammed into iPSCs before being differentiated into CMs using small molecules or cytokines. The second approach consists of a direct reprogramming of the skin fibroblast into iCMs. In both cases, the CMs produced in vitro have to be injected into the patient. When considering in situ reprogramming, the transcription factors (carried by viruses) are directly delivered to the patient and TFs will be expressed in cardiac fibroblasts, reprogramming them directly into iCMs. OKSM factors: Oct4, Sox2, Klf4, c-Myc.
Mentions: The in vitro demonstration of direct fibroblast reprogramming previously discussed was performed on embryonic, neonatal, adult tail-tip, skin and cardiac fibroblasts.5,141,142 Fibroblasts have long been considered as of uniform cell type across different tissues.150,151 Morphologically they are flat, spindle-shaped cells with multiple processes emanating from the main cell body. They can be defined as mesenchymal cells producing extracellular matrix (ECM) components like collagens and fibronectin.152 This simple morphological definition highlighted a mistaken identity with mesenchymal stromal/stem cells (MSCs).153 This view has now been challenged by the demonstration of phenotypic heterogeneity of fibroblast from different tissues in different conditions.151 This heterogeneity poses an active area of investigation for direct reprogramming methods to focus on the most appropriate fibroblasts. But which fibroblast populations are the most appropriate to focus on? To answer this question, we might first need to address the question of the different strategies that can be foreseen using this direct reprogramming technique. Indeed, two types of therapy (summarized in Figure 7) can be envisioned using direct reprogramming.

Bottom Line: Treatment of cardiovascular diseases remains challenging considering the limited regeneration capacity of the heart muscle.Developments of reprogramming strategies to create in vitro and in vivo cardiomyocytes have been the focus point of a considerable amount of research in the past decades.The choice of cells to employ, the state-of-the-art methods for different reprogramming strategies, and their promises and future challenges before clinical entry, are all discussed here.

View Article: PubMed Central - PubMed

Affiliation: Qatar Cardiovascular Research Center, Qatar Foundation-Education City, Doha, Qatar.

ABSTRACT
Treatment of cardiovascular diseases remains challenging considering the limited regeneration capacity of the heart muscle. Developments of reprogramming strategies to create in vitro and in vivo cardiomyocytes have been the focus point of a considerable amount of research in the past decades. The choice of cells to employ, the state-of-the-art methods for different reprogramming strategies, and their promises and future challenges before clinical entry, are all discussed here.

No MeSH data available.


Related in: MedlinePlus