Cardiac Tissue Engineering for the Treatment of Myocardial Infarction

Yu, Dae Young; Wang, Xiaowei; Ye, Lei

doi:10.3390/jcdd8110153

Cited by 8 publications

(7 citation statements)

References 108 publications

(164 reference statements)

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“…Long-term culture 12 , 13 , drug selection, metabolism 16 , 17 , mechanical stimulus 46 , 47 , tissue engineering 14 , 15 , electrical stimulus 48 , microRNA 49 , cell-cell interaction 15 , growth hormones 50 , 51 , and modulation of signaling pathways, such as mTOR 52 and WNT 53 , have been shown to more or less efficiently promote maturation of hPSC-CMs. In the current study, we showed that AA, which is also called vitamin C and is an essential nutrient, promoted MLC2v protein expression in hiPSC-CMs.…”

Section: Discussionmentioning

confidence: 99%

Ascorbic acid induces MLC2v protein expression and promotes ventricular-like cardiomyocyte subtype in human induced pluripotent stem cells derived cardiomyocytes

Gao¹,

Su²,

Wei³

et al. 2023

Theranostics

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Introduction: The potentially unlimited number of cardiomyocyte (CMs) derived from human induced pluripotent stem cells (hiPSCs) in vitro facilitates high throughput applications like cell transplantation for myocardial repair, disease modelling, and cardiotoxicity testing during drug development. Despite promising progress in these areas, a major disadvantage that limits the use of hiPSC derived CMs (hiPSC-CMs) is their immaturity. Methods : Three hiPSC lines (PCBC-hiPSC, DP3-hiPSCs, and MLC2v-mEGFP hiPSC) were differentiated into CMs (PCBC-CMs, DP3-CMs, and MLC2v-CMs, respectively) with or without retinoic acid (RA). hiPSC-CMs were either maintained up to day 30 of contraction (D30C), or D60C, or purified using lactate acid and used for experiments. Purified hiPSC-CMs were cultured in basal maturation medium (BMM) or BMM supplemented with ascorbic acid (AA) for 14 days. The AA treated and non-treated hiPSC-CMs were characterized for sarcomeric proteins (MLC2v, TNNI3, and MYH7), ion channel proteins (Kir2.1, Nav1.5, Cav1.2, SERCA2a, and RyR), mitochondrial membrane potential, metabolomics, and action potential. Bobcat339, a selective and potent inhibitor of DNA demethylation, was used to determine whether AA promoted hiPSC-CM maturation through modulating DNA demethylation. Results: AA significantly increased MLC2v expression in PCBC-CMs, DP3-CMs, MLC2v-CMs, and RA induced atrial-like PCBC-CMs. AA treatment significantly increased mitochondrial mass, membrane potential, and amino acid and fatty acid metabolism in PCBC-CMs. Patch clamp studies showed that AA treatment induced PCBC-CMs and DP3-CMs adaptation to a ventricular-like phenotype. Bobcat339 inhibited MLC2v protein expression in AA treated PCBC-CMs and DP3-CMs. DNA demethylation inhibition was also associated with reduced TET1 and TET2 protein expressions and reduced accumulation of the oxidative product, 5 hmC, in both PCBC-CMs and DP3-CMs, in the presence of AA. Conclusions: Ascorbic acid induced MLC2v protein expression and promoted ventricular-like CM subtype in hiPSC-CMs. The effect of AA on hiPSC-CM was attenuated with inhibition of TET1/TET2 mediated DNA demethylation.

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Section: Discussionmentioning

confidence: 99%

Ascorbic acid induces MLC2v protein expression and promotes ventricular-like cardiomyocyte subtype in human induced pluripotent stem cells derived cardiomyocytes

Gao¹,

Su²,

Wei³

et al. 2023

Theranostics

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“…(b) Tissue engineering: Techniques are developed to create viable cardiac tissue grafts from iPSCs, using biodegradable scaffolds that support cell growth and integration. These tissues can replace a damaged myocardium and incorporate features like electrical conductivity to boost functional integration [21,22]. (c) Genetic modifications: iPSCs are genetically modified to improve survival, proliferation, and differentiation.…”

Section: Induced Pluripotent Stem Cells (Ipscs)mentioning

confidence: 99%

Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics

Kumar,

Mishra,

Tran

et al. 2024

Cells

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Cardiovascular diseases continue to challenge global health, demanding innovative therapeutic solutions. This review delves into the transformative role of mesenchymal stem cells (MSCs) in advancing cardiovascular therapeutics. Beginning with a historical perspective, we trace the development of stem cell research related to cardiovascular diseases, highlighting foundational therapeutic approaches and the evolution of cell-based treatments. Recognizing the inherent challenges of MSC-based cardiovascular therapeutics, which range from understanding the pro-reparative activity of MSCs to tailoring patient-specific treatments, we emphasize the need to refine the pro-regenerative capacity of these cells. Crucially, our focus then shifts to the strategies of the fourth generation of cell-based therapies: leveraging the secretomic prowess of MSCs, particularly the role of extracellular vesicles; integrating biocompatible scaffolds and artificial sheets to amplify MSCs’ potential; adopting three-dimensional ex vivo propagation tailored to specific tissue niches; harnessing the promise of genetic modifications for targeted tissue repair; and institutionalizing good manufacturing practice protocols to ensure therapeutic safety and efficacy. We conclude with reflections on these advancements, envisaging a future landscape redefined by MSCs in cardiovascular regeneration. This review offers both a consolidation of our current understanding and a view toward imminent therapeutic horizons.

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“…Collagen, the most abundant structural protein in the body, is also one of the most common natural polymers used to engineer the heart [192][193][194]. Other natural polymers used to produce engineered heart include gelatin [195][196][197], alginate [198,199], chitosan [200,201], fibrin [202,203], silk [204][205][206], and decellularized matrices [159,207,208].…”

Section: Biomaterials In Cardiac Tissue Engineeringmentioning

confidence: 99%

“…Scaffolds, hydrogels Bioactivity, biocompatability, biodegradability, low toxicity, low cost [195][196][197] Alginate Scaffolds, hydrogels Biocompatability, biodegradability, non-adhesive, ease of modification, low toxicity, low cost [198,199] Chitosan Scaffolds, hydrogels Biocompatability, biodegradability, ease of modification, antimicrobial, low toxicity, low cost [200,201] Fibrin Scaffolds, hydrogels Bioactivity, biocompatability, biodegradability, ease of fabrication, low toxicity [202,203] Silk Scaffolds, hydrogels Bioactivity, biocompatibility, dynamic biodegradability, ease of modification, mechanical strength, low toxicity [204][205][206] ECM Scaffolds, hydrogels Bioactivity, biodegradability, endogenous integration, replication of complex native microenvironment [159,207,208] Polyethylene glycol (PEG)…”

Section: Gelatinmentioning

confidence: 99%

Engineering the cardiac tissue microenvironment

Ronan,

Bahcecioglu,

Aliyev

et al. 2023

Prog. Biomed. Eng.

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In this article we review the microfabrication approaches, with a focus on bioprinting and organ-on-chip technologies, used to engineer cardiac tissue. First, we give a brief introduction to heart anatomy and physiology, and the developmental stages of the heart from fetal stages to adulthood. We also give information on the cardiac tissue microenvironment, including the cells residing in the heart, the biochemical composition and structural organization of the heart extracellular matrix, the signaling factors playing roles in heart development and maturation, and their interactions with one another. We then give a brief summary of both cardiovascular diseases and the current treatment methods used in the clinic to treat these diseases. Second, we explain how tissue engineering recapitulates the development and maturation of the normal or diseased heart microenvironment by spatially and temporally incorporating cultured cells, biomaterials, and growth factors (GF). We briefly expand on the cells, biomaterials, and GFs used to engineer the heart, and the limitations of their use. Next, we review the state-of-the-art tissue engineering approaches, with a special focus on bioprinting and heart-on-chip technologies, intended to (i) treat or replace the injured cardiac tissue, and (ii) create cardiac disease models to study the basic biology of heart diseases, develop drugs against these diseases, and create diagnostic tools to detect heart diseases. Third, we discuss the recent trends in cardiac tissue engineering, including the use of machine learning, CRISPR/Cas editing, exosomes and microRNAs, and immune modeling in engineering the heart. Finally, we conclude our article with a brief discussion on the limitations of cardiac tissue engineering and our suggestions to engineer more reliable and clinically relevant cardiac tissues.

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Cardiac Tissue Engineering for the Treatment of Myocardial Infarction

Cited by 8 publications

References 108 publications

Ascorbic acid induces MLC2v protein expression and promotes ventricular-like cardiomyocyte subtype in human induced pluripotent stem cells derived cardiomyocytes

Ascorbic acid induces MLC2v protein expression and promotes ventricular-like cardiomyocyte subtype in human induced pluripotent stem cells derived cardiomyocytes

Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics

Engineering the cardiac tissue microenvironment

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