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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

Microgrooved culture substrates' effect on calcium cycling of cardiac myocytes derived from human-induced pluripotent stem cells. Representative immunofluorescence of iPSC-CM cultured on unstructured polydimethylsiloxane (A) and microgrooved polydimethylsiloxane (B), Red - sarcomeric a-actin, Blue - DAPI, scale bar 20 mm.Quantification of cell alignment iPSC-CM on structured and unstructured constructs (C). (Adapted from Ref.78)
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fig4: Microgrooved culture substrates' effect on calcium cycling of cardiac myocytes derived from human-induced pluripotent stem cells. Representative immunofluorescence of iPSC-CM cultured on unstructured polydimethylsiloxane (A) and microgrooved polydimethylsiloxane (B), Red - sarcomeric a-actin, Blue - DAPI, scale bar 20 mm.Quantification of cell alignment iPSC-CM on structured and unstructured constructs (C). (Adapted from Ref.78)

Mentions: Beyond the differentiation protocol improvements, much work focused on the maturation of PSCs derived CMs. Indeed, the maturity of generated CMs remains a critical bottleneck. For instance, despite the fact that iPSCs derived CMs present most of the characteristics of adult CMs (self-induced action potential, proteins/genes expression), the generated cells lack maturity for the most part (non-expression of mlc2v contractile protein, lack of organization, absence of M-band etc) and more closely resemble embryonic CMs than adult CMs.103 A remarkable publication by Murry and colleagues104 showed that implantation of a large number of human embryonic stem cell-derived CMs in non-human primates following heart failure could lead to re-muscularization of infarcted heart and even electromechanical junctions with surrounding muscle, but even over a three month period, cells failed to completely mature, and the non-human primate ultimately experienced arrhythmic complications. Long term culture of PSC derived CMs has been shown to improve the maturity of differentiating cells, but remains of restricted interest for potential clinical applications.105 Our group and others have previously demonstrated that a forced alignment of the cells improves the maturity of the CMs generated78,106 (Figure 4). The mechanical and electrical stimulation of derived CMs has also been proven to favor maturation of cells toward an adult phenotype.107,108 Besides, the use of scaffolds for maturation of CMs may lead to their potential interest for clinical use.


Reprogramming for cardiac regeneration.

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

Microgrooved culture substrates' effect on calcium cycling of cardiac myocytes derived from human-induced pluripotent stem cells. Representative immunofluorescence of iPSC-CM cultured on unstructured polydimethylsiloxane (A) and microgrooved polydimethylsiloxane (B), Red - sarcomeric a-actin, Blue - DAPI, scale bar 20 mm.Quantification of cell alignment iPSC-CM on structured and unstructured constructs (C). (Adapted from Ref.78)
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4352683&req=5

fig4: Microgrooved culture substrates' effect on calcium cycling of cardiac myocytes derived from human-induced pluripotent stem cells. Representative immunofluorescence of iPSC-CM cultured on unstructured polydimethylsiloxane (A) and microgrooved polydimethylsiloxane (B), Red - sarcomeric a-actin, Blue - DAPI, scale bar 20 mm.Quantification of cell alignment iPSC-CM on structured and unstructured constructs (C). (Adapted from Ref.78)
Mentions: Beyond the differentiation protocol improvements, much work focused on the maturation of PSCs derived CMs. Indeed, the maturity of generated CMs remains a critical bottleneck. For instance, despite the fact that iPSCs derived CMs present most of the characteristics of adult CMs (self-induced action potential, proteins/genes expression), the generated cells lack maturity for the most part (non-expression of mlc2v contractile protein, lack of organization, absence of M-band etc) and more closely resemble embryonic CMs than adult CMs.103 A remarkable publication by Murry and colleagues104 showed that implantation of a large number of human embryonic stem cell-derived CMs in non-human primates following heart failure could lead to re-muscularization of infarcted heart and even electromechanical junctions with surrounding muscle, but even over a three month period, cells failed to completely mature, and the non-human primate ultimately experienced arrhythmic complications. Long term culture of PSC derived CMs has been shown to improve the maturity of differentiating cells, but remains of restricted interest for potential clinical applications.105 Our group and others have previously demonstrated that a forced alignment of the cells improves the maturity of the CMs generated78,106 (Figure 4). The mechanical and electrical stimulation of derived CMs has also been proven to favor maturation of cells toward an adult phenotype.107,108 Besides, the use of scaffolds for maturation of CMs may lead to their potential interest for clinical use.

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