In vivo  reprogramming for heart regeneration: A glance at efficiency, environmental impacts, challenges and future directions

Ebrahimi, Behnam

doi:10.1016/j.yjmcc.2017.05.005

Cited by 22 publications

(16 citation statements)

References 90 publications

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“…Moreover, in vivo evaluation showed that both conductive and non-conductive GelMA-based scaffolds led to the preservation of normal tissue architecture by minimizing cardiac remodeling after MI. These observations could be explained in part due to the complex interplay of different bioactive cues that are normally present in vivo [73][74][75][76], which were not replicated in our experiments in vitro. Furthermore, these results demonstrated that cardiac remodeling could be effectively prevented using acellular scaffolds without the need for exogenous cytokines or growth factors, which is highly advantageous for the clinical translation of these scaffolds.…”

Section: In Vitro Contractile Activity and Phenotype Of Cms Cultured mentioning

confidence: 72%

Engineering a naturally-derived adhesive and conductive cardiopatch

et al. 2019

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Myocardial infarction (MI) leads to a multi-phase reparative process at the site of damaged heart that ultimately results in the formation of non-conductive fibrous scar tissue. Despite the widespread use of electroconductive biomaterials to increase the physiological relevance of bioengineered cardiac tissues in vitro, there are still several limitations associated with engineering biocompatible scaffolds with appropriate mechanical properties and electroconductivity for cardiac tissue regeneration. Here, we introduce highly adhesive fibrous scaffolds engineered by electrospinning of gelatin methacryloyl (GelMA) followed by the conjugation of a choline-based bio-ionic liquid (Bio-IL) to develop conductive and adhesive cardiopatches. These GelMA/Bio-IL adhesive patches were optimized to exhibit mechanical and conductive properties similar to the native myocardium. Furthermore, the engineered patches strongly adhered to murine myocardium due to the formation of ionic bonding between the Bio-IL and native tissue, eliminating the need for suturing. Co-cultures of primary cardiomyocytes and cardiac fibroblasts grown on GelMA/Bio-IL patches exhibited comparatively better contractile profiles compared to pristine GelMA controls, as demonstrated by over-expression of the gap junction protein connexin 43. These cardiopatches could be used to provide mechanical support and restore electromechanical coupling at the site of MI to minimize cardiac remodeling and preserve normal cardiac function.

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Section: In Vitro Contractile Activity and Phenotype Of Cms Cultured mentioning

confidence: 72%

Engineering a naturally-derived adhesive and conductive cardiopatch

et al. 2019

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“…Furthermore, in the last decade, emerging studies have raised a new intriguing possibility for myocardial regeneration, represented by the direct reprogramming of fibroblasts into CMs. Considering the abundance of cardiac fibroblasts in the heart, the possibility for their direct reprogramming is expected to revolutionize therapies for myocardial regeneration by the direct conversion of dysfunctional fibrotic scar into contractile myocardial tissue [ 12 , 13 , 14 , 15 , 16 ]. Alternatively, the possibility to directly convert fibroblasts into CMs could also be exploited for in vitro generation of autologous CMs for the cellularization of implantable hydrogels and patches.…”

Section: Introductionmentioning

confidence: 99%

Impact of Biomaterials on Differentiation and Reprogramming Approaches for the Generation of Functional Cardiomyocytes

Paoletti

Divieto

Chiono

2018

Cells

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The irreversible loss of functional cardiomyocytes (CMs) after myocardial infarction (MI) represents one major barrier to heart regeneration and functional recovery. The combination of different cell sources and different biomaterials have been investigated to generate CMs by differentiation or reprogramming approaches although at low efficiency. This critical review article discusses the role of biomaterial platforms integrating biochemical instructive cues as a tool for the effective generation of functional CMs. The report firstly introduces MI and the main cardiac regenerative medicine strategies under investigation. Then, it describes the main stem cell populations and indirect and direct reprogramming approaches for cardiac regenerative medicine. A third section discusses the main techniques for the characterization of stem cell differentiation and fibroblast reprogramming into CMs. Another section describes the main biomaterials investigated for stem cell differentiation and fibroblast reprogramming into CMs. Finally, a critical analysis of the scientific literature is presented for an efficient generation of functional CMs. The authors underline the need for biomimetic, reproducible and scalable biomaterial platforms and their integration with external physical stimuli in controlled culture microenvironments for the generation of functional CMs.

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“…This furthered for searching factors that could drive the transdifferentiation of the abundant population of CFs found in the scar of MI zones, into therapeutically suitable cells, such as CMs. At present, combinations of transcription factors (TFs), miRNAs, and other agents have been tested for their ability to guide the transdifferentiation of fibroblasts into induced CMs (iCMs), both in vitro and in vivo [ 68 ]. Preliminary results of in vivo transdifferentiation of CFs showed encouraging improvements in MI rodent models [ 69 – 71 ].…”

Section: The Stem Cell Therapy Approachmentioning

confidence: 99%

Nanotechnology-Based Cardiac Targeting and Direct Cardiac Reprogramming: The Betrothed

Passaro

Testa

Ambrosone

et al. 2017

Stem Cells International

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Cardiovascular diseases represent the first cause of morbidity in Western countries, and chronic heart failure features a significant health care burden in developed countries. Efforts in the attempt of finding new possible strategies for the treatment of CHF yielded several approaches based on the use of stem cells. The discovery of direct cardiac reprogramming has unveiled a new approach to heart regeneration, allowing, at least in principle, the conversion of one differentiated cell type into another without proceeding through a pluripotent intermediate. First developed for cancer treatment, nanotechnology-based approaches have opened new perspectives in many fields of medical research, including cardiovascular research. Nanotechnology could allow the delivery of molecules with specific biological activity at a sustained and controlled rate in heart tissue, in a cell-specific manner. Potentially, all the mediators and structural molecules involved in the fibrotic process could be selectively targeted by nanocarriers, but to date, only few experiences have been made in cardiac research. This review highlights the most prominent concepts that characterize both the field of cardiac reprogramming and a nanomedicine-based approach to cardiovascular diseases, hypothesizing a possible synergy between these two very promising fields of research in the treatment of heart failure.

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In vivo reprogramming for heart regeneration: A glance at efficiency, environmental impacts, challenges and future directions

Cited by 22 publications

References 90 publications

Engineering a naturally-derived adhesive and conductive cardiopatch

Engineering a naturally-derived adhesive and conductive cardiopatch

Impact of Biomaterials on Differentiation and Reprogramming Approaches for the Generation of Functional Cardiomyocytes

Nanotechnology-Based Cardiac Targeting and Direct Cardiac Reprogramming: The Betrothed

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