In vitro CSC-derived cardiomyocytes exhibit the typical microRNA-mRNA blueprint of endogenous cardiomyocytes

Scalise, Mariangela; Marino, Fabiola; Salerno, Luca; Mancuso, Teresa; Cappetta, Donato; Barone, Antonella; Parrotta, Elvira Immacolata; Torella, Annalaura; Palumbo, Domenico; Veltri, Pierangelo; Angelis, Antonella De; Berrino, Liberato; Rossi, Francesco; Weisz, Alessandro; Rota, Marcello; Urbanek, Konrad; Nadal‐Ginard, Bernardo; Torella, Daniele; Cianflone, Eleonora

doi:10.1038/s42003-021-02677-y

Cited by 18 publications

(34 citation statements)

References 110 publications

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“…When placed in laminin-coated plastic dishes with LIF-deprived basic differentiation medium for 14 days, the peripheral cells of the spheres expressed high levels of smooth muscle as well as endothelial and cardiac lineages. Nevertheless, the CM derived from cloned CSCs still reach a biochemical myogenic differentiation that is intermediate between fetal and neonatal cardiomyocytes [150]. These data have also been confirmed by RNASeq expression profile analysis.…”

Section: From Cardiac Spheroids To Cardioidssupporting

confidence: 53%

“…Comparison of transcriptome and miRNome between clonal CSCs, contracting cardiomyocytes obtained from CSC-derived cardiospheres (iCMs), and adult cardiomyocytes (aCMs) has shown that CSCs are cardiomyogenic since they activate the entire gene network and specific cardiomyo-miRs characteristic of the aCMs phenotype. Yet, in concordance with the immature phenotype of iCMs, the expression of these miRNAs is still significantly lower than in aCMs, falling between CSCs and aCMs [150]. Cardiosphere attachment on laminin or 0,1% gelatin plates alters cell shape and geometry, leading to cell flattening and changes in the cytoskeleton and nuclear shape.…”

Section: From Cardiac Spheroids To Cardioidsmentioning

confidence: 95%

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From Spheroids to Organoids: The Next Generation of Model Systems of Human Cardiac Regeneration in a Dish

Scalise

Marino

Salerno

et al. 2021

IJMS

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Organoids are tiny, self-organized, three-dimensional tissue cultures that are derived from the differentiation of stem cells. The growing interest in the use of organoids arises from their ability to mimic the biology and physiology of specific tissue structures in vitro. Organoids indeed represent promising systems for the in vitro modeling of tissue morphogenesis and organogenesis, regenerative medicine and tissue engineering, drug therapy testing, toxicology screening, and disease modeling. Although 2D cell cultures have been used for more than 50 years, even for their simplicity and low-cost maintenance, recent years have witnessed a steep rise in the availability of organoid model systems. Exploiting the ability of cells to re-aggregate and reconstruct the original architecture of an organ makes it possible to overcome many limitations of 2D cell culture systems. In vitro replication of the cellular micro-environment of a specific tissue leads to reproducing the molecular, biochemical, and biomechanical mechanisms that directly influence cell behavior and fate within that specific tissue. Lineage-specific self-organizing organoids have now been generated for many organs. Currently, growing cardiac organoid (cardioids) from pluripotent stem cells and cardiac stem/progenitor cells remains an open challenge due to the complexity of the spreading, differentiation, and migration of cardiac muscle and vascular layers. Here, we summarize the evolution of biological model systems from the generation of 2D spheroids to 3D organoids by focusing on the generation of cardioids based on the currently available laboratory technologies and outline their high potential for cardiovascular research.

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Section: From Cardiac Spheroids To Cardioidssupporting

confidence: 53%

Section: From Cardiac Spheroids To Cardioidsmentioning

confidence: 95%

From Spheroids to Organoids: The Next Generation of Model Systems of Human Cardiac Regeneration in a Dish

Scalise

Marino

Salerno

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Adult CSCs are multipotent, and when grown in a specific differentiation medium acquire the phenotype of the three main cardiac cells (cardiomyocytes, smooth muscle and endothelial cells). However, cardiomyocyte derived from clonal CSCs showed a phenotype that more closely resembles neonatal, immature cardiomyocytes compared with the adult, terminally differentiated cardiomyocytes [ 89 ]. Contracting cardiomyocyte derived from clonal CSCs have an intermediate transcriptional profile with the levels of mRNA of transcription factors and myofilament proteins that fall between fetal and neonatal cardiomyocytes.…”

Section: Diabetes and Cardiac Stem Cell Biologymentioning

confidence: 99%

“…Cardiomyocyte derived from CSCs up-regulate the cardiomyo-miRs (miR-1a 3p, miR-133a-1, miR-133a-2, miR-204, miR-335, miR-486, miR-490, and miR-499) to a lower extent than adult cardiomyocytes. However, the specific networks of miRNA/mRNAs operative in CSC-derived cardiomyocytes closely resembled those of adult cardiomyocytes [ 89 ].…”

Section: Diabetes and Cardiac Stem Cell Biologymentioning

confidence: 99%

Unraveling and Targeting Myocardial Regeneration Deficit in Diabetes

et al. 2022

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Cardiomyopathy is a common complication in diabetic patients. Ventricular dysfunction without coronary atherosclerosis and hypertension is driven by hyperglycemia, hyperinsulinemia and impaired insulin signaling. Cardiomyocyte death, hypertrophy, fibrosis, and cell signaling defects underlie cardiomyopathy. Notably, detrimental effects of the diabetic milieu are not limited to cardiomyocytes and vascular cells. The diabetic heart acquires a senescent phenotype and also suffers from altered cellular homeostasis and the insufficient replacement of dying cells. Chronic inflammation, oxidative stress, and metabolic dysregulation damage the population of endogenous cardiac stem cells, which contribute to myocardial cell turnover and repair after injury. Therefore, deficient myocardial repair and the progressive senescence and dysfunction of stem cells in the diabetic heart can represent potential therapeutic targets. While our knowledge of the effects of diabetes on stem cells is growing, several strategies to preserve, activate or restore cardiac stem cell compartments await to be tested in diabetic cardiomyopathy.

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“…The transmission of dyes via gap junctions between CSCs and CMs or fibroblasts was demonstrated previously and verified the functional coupling of these three cell populations[ 97 ]. In addition, micro ribonucleic acid (miRNA-499) translocates from CMs to CSCs comprising to the initiation of lineage specification and formation of myocytes[ 103 ].…”

Section: Transcriptome and Regenerative Capacity Of Sub-populationsmentioning

confidence: 99%

Cardiac stem cells: Current knowledge and future prospects

Mehanna¹,

Essawy²,

Barkat³

et al. 2022

WJSC

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Regenerative medicine is the field concerned with the repair and restoration of the integrity of damaged human tissues as well as whole organs. Since the inception of the field several decades ago, regenerative medicine therapies, namely stem cells, have received significant attention in preclinical studies and clinical trials. Apart from their known potential for differentiation into the various body cells, stem cells enhance the organ's intrinsic regenerative capacity by altering its environment, whether by exogenous injection or introducing their products that modulate endogenous stem cell function and fate for the sake of regeneration. Recently, research in cardiology has highlighted the evidence for the existence of cardiac stem and progenitor cells (CSCs/CPCs). The global burden of cardiovascular diseases’ morbidity and mortality has demanded an in-depth understanding of the biology of CSCs/CPCs aiming at improving the outcome for an innovative therapeutic strategy. This review will discuss the nature of each of the CSCs/CPCs, their environment, their interplay with other cells, and their metabolism. In addition, important issues are tackled concerning the potency of CSCs/CPCs in relation to their secretome for mediating the ability to influence other cells. Moreover, the review will throw the light on the clinical trials and the preclinical studies using CSCs/CPCs and combined therapy for cardiac regeneration. Finally, the novel role of nanotechnology in cardiac regeneration will be explored.

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In vitro CSC-derived cardiomyocytes exhibit the typical microRNA-mRNA blueprint of endogenous cardiomyocytes

Cited by 18 publications

References 110 publications

From Spheroids to Organoids: The Next Generation of Model Systems of Human Cardiac Regeneration in a Dish

From Spheroids to Organoids: The Next Generation of Model Systems of Human Cardiac Regeneration in a Dish

Unraveling and Targeting Myocardial Regeneration Deficit in Diabetes

Cardiac stem cells: Current knowledge and future prospects

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