Role of somatic cell sources in the maturation degree of human induced pluripotent stem cell-derived cardiomyocytes

Pianezzi, Enea; Altomare, Claudia; Bolis, Sara; Balbi, Carolina; Torre, Tiziano; Rinaldi, Andrea; Camici, Giovanni G.; Barile, Lucio; Vassalli, Giuseppe

doi:10.1016/j.bbamcr.2019.118538

Cited by 34 publications

(36 citation statements)

References 29 publications

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“…Intra-myocardial administration of EVs soon after injury (i.e., myocardial infarction) has been shown to provide beneficial paracrine effects addressing both cardiac repair and regenerative mechanisms, resulting in long-term effects after a single acute injection [89,90,155,218]. Nevertheless, paracrine effects are well known to act promptly and locally, therefore follow-up administration would be the ideal treatment regime, especially to modulate cardiac detrimental pathological cardiac remodelling over time.…”

Section: Looking For the Right Address: Improving Ev Cardiac Tropismmentioning

confidence: 99%

Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation

Balbi

Costa

Barile

2020

Cells

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Ischaemic cardiac disease is associated with a loss of cardiomyocytes and an intrinsic lack of myocardial renewal. Recent work has shown that the heart retains limited cardiomyocyte proliferation, which remains inefficient when facing pathological conditions. While broadly active in the neonatal mammalian heart, this mechanism becomes quiescent soon after birth, suggesting loss of regenerative potential with maturation into adulthood. A key question is whether this temporary regenerative window can be enhanced via appropriate stimulation and further extended. Recently the search for novel therapeutic approaches for heart disease has centred on stem cell biology. The "paracrine effect" has been proposed as a promising strategy to boost endogenous reparative and regenerative mechanisms from within the cardiac tissue by exploiting the modulatory potential of soluble stem cell-secreted factors. As such, growing interest has been specifically addressed towards stem/progenitor cell-secreted extracellular vesicles (EVs), which can be easily isolated in vitro from cell-conditioned medium. This review will provide a comprehensive overview of the current paradigm on cardiac repair and regeneration, with a specific focus on the role and mechanism(s) of paracrine action of EVs from cardiac stromal progenitors as compared to exogenous stem cells in order to discuss the optimal choice for future therapy. In addition, the challenges to overcoming translational EV biology from bench to bedside for future cardiac regenerative medicine will be discussed.

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Section: Looking For the Right Address: Improving Ev Cardiac Tropismmentioning

confidence: 99%

Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation

Balbi

Costa

Barile

2020

Cells

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“…al. in their recent paper showed that iPSCs from cardiac somatic cell sources differentiated into mature cardiomyocytes more efficiently compared to the cells from non-cardiac somatic cell sources 28 .…”

Section: Discussionmentioning

confidence: 98%

“…Importantly, for clinical application purposes, the source of the cell type used for reprogramming and differentiation seems to play a critical role 26 . Ideally, somatic cells should be easily accessible, have the potential to proliferate 27 and, according to the so called "epigenetic memory" hypothesis, have similar embryonic origin 28 . In general, the discussion on "epigenetic memory" is controversial and extremely interesting.…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific promoter-based reporter system for monitoring cell differentiation from iPSCs to cardiomyocytes

Fiedorowicz

Rozwadowska

Zimna

et al. 2020

Sci Rep

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The possibility of using stem cell-derived cardiomyocytes opens a new platform for modeling cardiac cell differentiation and disease or the development of new drugs. Progress in this field can be accelerated by high-throughput screening (HTS) technology combined with promoter reporter system. The goal of the study was to create and evaluate a responsive promoter reporter system that allows monitoring of iPSC differentiation towards cardiomyocytes. The lentiviral promoter reporter system was based on troponin 2 (TNNT2) and alpha cardiac actin (ACTC) with firefly luciferase and mCherry, respectively. The system was evaluated in two in vitro models. vitro cell culture (confirmed by I-FISH, ddPCR, qPCR). Second, differentiated and contracting control cardiomyocytes (obtained from control non-reporter transduced iPSCs) were subsequently transduced with TNNT2-luc-T2A-Puro-CMV-GFP and hACTC-mcherry-WPRE-EF1-Neo lentiviruses to observe the functionality of obtained cardiomyocytes. Our results indicated that the reporter modified cell lines can be used for HTS applications, but it is essential to monitor the stability of the reporter sequence during extended cell in vitro culture. First, system followed the differentiation of TNNT2-luc-T2A-Puro-mCMV-GFP and hACTC-mcherry-WPRE-EF1-Neo from transduced iPSC line towards cardiomyocytes and revealed the significant decrease in both inserts copy number during the prolonged in

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“…In agreement with these observations, it has been recently reported the possibility to reprogram explant-derived cells, elsewhere referred as cardiac progenitor cells (CPCs) [125], from human cardiac biopsies obtain functional and terminal differentiated CMs [29]. As schematized in Figure 4, CPC-derived hiPSCs account for improvements in differentiation to CMs in comparison to patient-matched hiPSCs from other somatic sources, such as bone marrow-derived mesenchymal stem cells (BMC) and dermal fibroblasts (HDF) both if cultured in monolayers [126] or EBs [127,128].…”

Section: Pluripotency and Cardiac Differentiation Of Hipscs Derived Fmentioning

confidence: 99%

“…Although hiPSC derived from HDFs have been described to produce a higher number of colonies that appear earlier in time, the expression level of pluripotency markers (e.g., Nanog, Oct4) resulted significantly enhanced in hiPSC from CPCs as compared to both hiPSC from HDFs and from BMCs [126,128]. Inversely, Sanchez-Freire et al [127] showed that the expression of pluripotency markers was not different between the two hiPSC lineages from different tissues.…”

Section: Pluripotency and Cardiac Differentiation Of Hipscs Derived Fmentioning

confidence: 99%

Human Induced Pluripotent Stem Cells Derived from a Cardiac Somatic Source: Insights for an In-Vitro Cardiomyocyte Platform

Lodrini

Barile

Rocchetti

et al. 2020

IJMS

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Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) has revolutionized the complex scientific field of disease modelling and personalized therapy. Cardiac differentiation of human iPSCs into cardiomyocytes (hiPSC-CMs) has been used in a wide range of healthy and disease models by deriving CMs from different somatic cells. Unfortunately, hiPSC-CMs have to be improved because existing protocols are not completely able to obtain mature CMs recapitulating physiological properties of human adult cardiac cells. Therefore, improvements and advances able to standardize differentiation conditions are needed. Lately, evidences of an epigenetic memory retained by the somatic cells used for deriving hiPSC-CMs has led to evaluation of different somatic sources in order to obtain more mature hiPSC-derived CMs.

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Role of somatic cell sources in the maturation degree of human induced pluripotent stem cell-derived cardiomyocytes

Cited by 34 publications

References 29 publications

Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation

Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation

Tissue-specific promoter-based reporter system for monitoring cell differentiation from iPSCs to cardiomyocytes

Human Induced Pluripotent Stem Cells Derived from a Cardiac Somatic Source: Insights for an In-Vitro Cardiomyocyte Platform

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