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Cardiomyocyte stem cells

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https://www.readbyqxmd.com/read/28213718/reprogramming-cell-fates-by-small-molecules
#1
REVIEW
Xiaojie Ma, Linghao Kong, Saiyong Zhu
Reprogramming cell fates towards pluripotent stem cells and other cell types has revolutionized our understanding of cellular plasticity. During the last decade, transcription factors and microRNAs have become powerful reprogramming factors for modulating cell fates. Recently, many efforts are focused on reprogramming cell fates by non-viral and non-integrating chemical approaches. Small molecules not only are useful in generating desired cell types in vitro for various applications, such as disease modeling and cell-based transplantation, but also hold great promise to be further developed as drugs to stimulate patients' endogenous cells to repair and regenerate in vivo...
February 17, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28211918/myotonic-dystrophy-type-1-patient-derived-ipscs-for-the-investigation-of-ctg-repeat-instability
#2
Junko Ueki, Masayuki Nakamori, Masahiro Nakamura, Misato Nishikawa, Yoshinori Yoshida, Azusa Tanaka, Asuka Morizane, Masayoshi Kamon, Toshiyuki Araki, Masanori P Takahashi, Akira Watanabe, Nobuya Inagaki, Hidetoshi Sakurai
Myotonic dystrophy type 1 (DM1) is an autosomal-dominant multi-system disease caused by expanded CTG repeats in dystrophia myotonica protein kinase (DMPK). The expanded CTG repeats are unstable and can increase the length of the gene with age, which worsens the symptoms. In order to establish a human stem cell system suitable for the investigation of repeat instability, DM1 patient-derived iPSCs were generated and differentiated into three cell types commonly affected in DM1, namely cardiomyocytes, neurons and myocytes...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203568/mirna-sequence-indicates-that-mesenchymal-stem-cells-and-exosomes-have-similar-mechanism-to-enhance-cardiac-repair
#3
Lianbo Shao, Yu Zhang, Beibei Lan, Juanjuan Wang, Zhiwei Zhang, Lulu Zhang, Pengli Xiao, Qingyou Meng, Yong-Jian Geng, Xi-Yong Yu, Yangxin Li
Mesenchymal stem cells (MSCs) repair infarcted heart through paracrine mechanism. We sought to compare the effectiveness of MSCs and MSC-derived exosomes (MSC-Exo) in repairing infarcted hearts and to identify how MSC-Exo mediated cardiac repair is regulated. In a rat myocardial infarction model, we found that MSC-Exo inhibited cardiac fibrosis, inflammation, and improved cardiac function. The beneficial effects of MSC-Exo were significantly superior compared to that of MSCs. To explore the potential mechanisms underlying MSC-Exo's effects, we performed several in vitro experiments and miRNA-sequence analysis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28202772/high-throughput-screening-of-tyrosine-kinase-inhibitor-cardiotoxicity-with-human-induced-pluripotent-stem-cells
#4
Arun Sharma, Paul W Burridge, Wesley L McKeithan, Ricardo Serrano, Praveen Shukla, Nazish Sayed, Jared M Churko, Tomoya Kitani, Haodi Wu, Alexandra Holmström, Elena Matsa, Yuan Zhang, Anusha Kumar, Alice C Fan, Juan C Del Álamo, Sean M Wu, Javid J Moslehi, Mark Mercola, Joseph C Wu
Tyrosine kinase inhibitors (TKIs), despite their efficacy as anticancer therapeutics, are associated with cardiovascular side effects ranging from induced arrhythmias to heart failure. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), generated from 11 healthy individuals and 2 patients receiving cancer treatment, to screen U.S. Food and Drug Administration-approved TKIs for cardiotoxicities by measuring alterations in cardiomyocyte viability, contractility, electrophysiology, calcium handling, and signaling...
February 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28197667/discovery-and-progress-of-direct-cardiac-reprogramming
#5
REVIEW
Hidenori Kojima, Masaki Ieda
Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs)...
February 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28194324/cell-therapies-in-cardiomyopathy-current-status-of-clinical-trials
#6
REVIEW
Ming Hao, Richard Wang, Wen Wang
Because the human heart has limited potential for regeneration, the loss of cardiomyocytes during cardiac myopathy and ischaemic injury can result in heart failure and death. Stem cell therapy has emerged as a promising strategy for the treatment of dead myocardium, directly or indirectly, and seems to offer functional benefits to patients. The ideal candidate donor cell for myocardial reconstitution is a stem-like cell that can be easily obtained, has a robust proliferation capacity and a low risk of tumour formation and immune rejection, differentiates into functionally normal cardiomyocytes, and is suitable for minimally invasive clinical transplantation...
2017: Analytical Cellular Pathology (Amsterdam)
https://www.readbyqxmd.com/read/28192031/neural-crest-stem-cells-can-differentiate-to-a-cardiomyogenic-lineage-with-an-ability-to-contract-in-response-to-pulsed-infrared-stimulation
#7
Jordan M Greenberg, Vicente Lumbreras, Daniel Pelaez, Suhrud M Rajguru, Herman S Cheung
INTRODUCTION: Cellular cardiomyoplasty has rapidly risen to prominence in the clinic following a myocardial infarction; however, low engraftment of transplanted cells limits the therapeutic benefit to these procedures. Recently, lineage-specific stem cells differentiated into cardiomyocytes have gained much attention to assist in the repair of an injured heart tissue; however, questions regarding the ideal cell source remain. In the present study, we have identified a source that is easy to extract stem cells from and show that the cells present have a high plasticity toward the cardiomyogenic lineage...
October 2016: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28191759/heparin-promotes-cardiac-differentiation-of-human-pluripotent-stem-cells-in-chemically-defined-albumin-free-medium-enabling-consistent-manufacture-of-cardiomyocytes
#8
Yongshun Lin, Kaari L Linask, Barbara Mallon, Kory Johnson, Michael Klein, Jeanette Beers, Wen Xie, Yubin Du, Chengyu Liu, Yinzhi Lai, Jizhong Zou, Mark Haigney, Hushan Yang, Mahendra Rao, Guokai Chen
Cardiomyocytes can be differentiated from human pluripotent stem cells (hPSCs) in defined conditions, but efficient and consistent cardiomyocyte differentiation often requires expensive reagents such as B27 supplement or recombinant albumin. Using a chemically defined albumin-free (E8 basal) medium, we identified heparin as a novel factor that significantly promotes cardiomyocyte differentiation efficiency, and developed an efficient method to differentiate hPSCs into cardiomyocytes. The treatment with heparin helped cardiomyocyte differentiation consistently reach at least 80% purity (up to 95%) from more than 10 different hPSC lines in chemically defined Dulbecco's modified Eagle's medium/F-12-based medium on either Matrigel or defined matrices like vitronectin and Synthemax...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28191018/thymosin-%C3%AE-4-improves-differentiation-and-vascularization-of-ehts
#9
Tilman Ziegler, Rabea Hinkel, Andrea Stöhr, Thomas Eschenhagen, Karl-Ludwig Laugwitz, Ferdinand le Noble, Robert David, Arne Hansen, Christian Kupatt
Induced pluripotent stem cells (iPSC) constitute a powerful tool to study cardiac physiology and represents a promising treatment strategy to tackle cardiac disease. However, iPSCs remain relatively immature after differentiation. Additionally, engineered heart tissue (EHT) has been investigated as a therapy option in preclinical disease models with promising results, although their vascularization and functionality leave room for improvement. Thymosin β4 (Tβ4) has been shown to promote the differentiation of progenitor cell lines to cardiomyocytes while it also induces angiogenic sprouting and vascular maturation...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28186692/targeted-genome-engineering-to-control-vegf-expression-in-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-potential-implications-for-the-treatment-of-myocardial-infarction
#10
Hyun-Min Cho, Pyung-Hwan Kim, Hyun-Kyung Chang, Yi-Ming Shen, Kwaku Bonsra, Byung-Jae Kang, Soo-Young Yum, Joo-Hyun Kim, So-Yeong Lee, Min-Cheol Choi, Hyongbum Henry Kim, Goo Jang, Je-Yoel Cho
Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) exhibit potency for the regeneration of infarcted hearts. Vascular endothelial growth factor (VEGF) is capable of inducing angiogenesis and can boost stem cell-based therapeutic effects. However, high levels of VEGF can cause abnormal blood vessel growth and hemangiomas. Thus, a controllable system to induce therapeutic levels of VEGF is required for cell therapy. We generated an inducible VEGF-secreting stem cell (VEGF/hUCB-MSC) that controls the expression of VEGF and tested the therapeutic efficacy in rat myocardial infarction (MI) model to apply functional stem cells to MI...
January 3, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28181589/developmental-stage-dependent-effects-of-cardiac-fibroblasts-on-function-of-stem-cell-derived-engineered-cardiac-tissues
#11
Brian Liau, Christopher P Jackman, Yanzhen Li, Nenad Bursac
We investigated whether the developmental stage of mouse cardiac fibroblasts (CFs) influences the formation and function of engineered cardiac tissues made of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs). Engineered cardiac tissue patches were fabricated by encapsulating pure mESC-CMs, mESC-CMs + adult CFs, or mESC-CMs + fetal CFs in fibrin-based hydrogel. Tissue patches containing fetal CFs exhibited higher velocity of action potential propagation and contractile force amplitude compared to patches containing adult CFs, while pure mESC-CM patches did not form functional syncytium...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174390/-surgical-regeneration-therapy-using-myoblast-sheets-for-severe-heart-failure
#12
Yoshiki Sawa
Heart failure is a life-threatening disorder worldwide, and the current end-stage therapies for severe heart failure are replacement therapies such as ventricular-assist devices and heart transplantation. Although these therapies have been reported to be useful, there are many issues in terms of the durability, complications, limited donors, adverse effect of continuous administration of immunosuppressive agents, and high costs involved. Recently, regenerative therapy based on genetic, cellular, or tissue engineering techniques has gained attention as a new therapy to overcome the challenges encountered in transplantation medicine...
January 2017: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/28174241/development-of-a-human-cardiac-organoid-injury-model-reveals-innate-regenerative-potential
#13
Holly K Voges, Richard J Mills, David A Elliott, Robert G Parton, Enzo R Porrello, James E Hudson
The adult human heart possesses a limited regenerative potential following an ischemic event, and undergoes a number of pathological changes in response to injury. While cardiac regeneration has been documented in zebrafish and neonatal mouse hearts, it is currently unknown whether the immature human heart is capable of undergoing complete regeneration. Combined progress in pluripotent stem cell differentiation and tissue engineering has facilitated the development of human cardiac organoids (hCO), which resemble fetal heart tissue and can be used to address this important knowledge gap...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28170287/intermediate-reprogramming-of-mouse-skin-fibroblasts-into-stem-like-cells-by-bone-morphogenetic-protein-4
#14
Seung-Eun Lee, Sang-Jun Uhm, Yeo-Jin Son, Yun-Gwi Park, Eun-Young Kim, Se-Pill Park
Specific transcription factors are sufficient to reprogram fully induced pluripotent stem cells or other types of cells. These findings raise the question of whether chemical molecules or proteins can replace transcription factors to alter the defined cell fate. In this study, we treated mouse skin fibroblasts (MSFs) with bone morphogenetic protein 4 (BMP4) and examined intermediate reprogramming of MSFs into stem-like cells. Putative epidermal stem cells isolated from the ventral skin epidermis of an adult mouse were used to confirm the reprogramming activity of BMP4, which increased the proliferation of these cells...
February 7, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28170198/differential-mechanisms-of-myocardial-conduction-slowing-by-adipose-tissue-derived-stromal-cells-derived-from-different-species
#15
Judith N Ten Sande, Nicoline W Smit, Mojtaba Parvizi, Shirley C M van Amersfoorth, Josée A Plantinga, Pascal F H M van Dessel, Jacques M T de Bakker, Marco C Harmsen, Ruben Coronel
Stem cell therapy is a promising therapeutic option to treat patients after myocardial infarction. However, the intramyocardial administration of large amounts of stem cells might generate a proarrhythmic substrate. Proarrhythmic effects can be explained by electrotonic and/or paracrine mechanisms. The narrow therapeutic time window for cell therapy and the presence of comorbidities limit the application of autologous cell therapy. The use of allogeneic or xenogeneic stem cells is a potential alternative to autologous cells, but differences in the proarrhythmic effects of adipose-derived stromal cells (ADSCs) across species are unknown...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28170197/enhanced-cardioprotection-by-human-endometrium-mesenchymal-stem-cells-driven-by-exosomal-microrna-21
#16
Kan Wang, Zhi Jiang, Keith A Webster, Jinghai Chen, Hengxun Hu, Yu Zhou, Jing Zhao, Lihan Wang, Yingchao Wang, Zhiwei Zhong, Cheng Ni, Qingju Li, Charlie Xiang, Ling Zhang, Rongrong Wu, Wei Zhu, Hong Yu, Xinyang Hu, Jian'an Wang
Our group recently reported positive therapeutic benefit of human endometrium-derived mesenchymal stem cells (EnMSCs) delivered to infarcted rat myocardium, an effect that correlated with enhanced secretion of protective cytokines and growth factors compared with parallel cultures of human bone marrow MSCs (BMMSCs). To define more precisely the molecular mechanisms of EnMSC therapy, in the present study, we assessed in parallel the paracrine and therapeutic properties of MSCs derived from endometrium, bone marrow, and adipose tissues in a rat model of myocardial infarction (MI)...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28170191/metabolomic-profiling-of-pompe-disease-induced-pluripotent-stem-cell-derived-cardiomyocytes-reveals-that-oxidative-stress-is-associated-with-cardiac-and-skeletal-muscle-pathology
#17
Yohei Sato, Hiroshi Kobayashi, Takashi Higuchi, Yohta Shimada, Hiroyuki Ida, Toya Ohashi
Pompe disease (PD) is a lysosomal storage disease that is caused by a deficiency of the acid α-glucosidase, which results in glycogen accumulation in the lysosome. The major clinical symptoms of PD include skeletal muscle weakness, respiratory failure, and cardiac hypertrophy. Based on its severity and symptom onset, PD is classified into infantile and late-onset forms. Lysosomal accumulation of glycogen can promote many types of cellular dysfunction, such as autophagic dysfunction, endoplasmic reticulum stress, and abnormal calcium signaling within skeletal muscle...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28169191/stem-cell-technology-in-cardiac-regeneration-a-pluripotent-stem-cell-promise
#18
REVIEW
Robin Duelen, Maurilio Sampaolesi
Despite advances in cardiovascular biology and medical therapy, heart disorders are the leading cause of death worldwide. Cell-based regenerative therapies become a promising treatment for patients affected by heart failure, but also underline the need for reproducible results in preclinical and clinical studies for safety and efficacy. Enthusiasm has been tempered by poor engraftment, survival and differentiation of the injected adult stem cells. The crucial challenge is identification and selection of the most suitable stem cell type for cardiac regenerative medicine...
January 27, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28169114/coculturing-with-endothelial-cells-promotes-in-vitro-maturation-and-electrical-coupling-of-human-embryonic-stem-cell-derived-cardiomyocytes
#19
Jennifer Pasquier, Renuka Gupta, Damien Rioult, Jessica Hoarau-Véchot, Raphael Courjaret, Khaled Machaca, Jassim Al Suwaidi, Edouard G Stanley, Shahin Rafii, David A Elliott, Charbel Abi Khalil, Arash Rafii
BACKGROUND: Pluripotent human embryonic stem cells (hESC) are a promising source of repopulating cardiomyocytes. We hypothesized that we could improve maturation of cardiomyocytes and facilitate electrical interconnections by creating a model that more closely resembles heart tissue; that is, containing both endothelial cells (ECs) and cardiomyocytes. METHODS: We induced cardiomyocyte differentiation in the coculture of an hESC line expressing the cardiac reporter NKX2...
January 10, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28167799/cell-population-structure-prior-to-bifurcation-predicts-efficiency-of-directed-differentiation-in-human-induced-pluripotent-cells
#20
Rhishikesh Bargaje, Kalliopi Trachana, Martin N Shelton, Christopher S McGinnis, Joseph X Zhou, Cora Chadick, Savannah Cook, Christopher Cavanaugh, Sui Huang, Leroy Hood
Steering the differentiation of induced pluripotent stem cells (iPSCs) toward specific cell types is crucial for patient-specific disease modeling and drug testing. This effort requires the capacity to predict and control when and how multipotent progenitor cells commit to the desired cell fate. Cell fate commitment represents a critical state transition or "tipping point" at which complex systems undergo a sudden qualitative shift. To characterize such transitions during iPSC to cardiomyocyte differentiation, we analyzed the gene expression patterns of 96 developmental genes at single-cell resolution...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
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