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Endogenous Cardiac Stem Cell

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https://www.readbyqxmd.com/read/29752948/functional-and-transcriptomic-insights-into-pathogenesis-of-r9c-phospholamban-mutation-using-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#1
Delaine K Ceholski, Irene C Turnbull, Chi-Wing Kong, Simon Koplev, Joshua Mayourian, Przemek A Gorski, Francesca Stillitano, Angelos A Skodras, Mathieu Nonnenmacher, Ninette Cohen, Johan L M Björkegren, Daniel R Stroik, Razvan L Cornea, David D Thomas, Ronald A Li, Kevin D Costa, Roger J Hajjar
Dilated cardiomyopathy (DCM) can be caused by mutations in the cardiac protein phospholamban (PLN). We used CRISPR/Cas9 to insert the R9C PLN mutation at its endogenous locus into a human induced pluripotent stem cell (hiPSC) line from an individual with no cardiovascular disease. R9C PLN hiPSC-CMs display a blunted β-agonist response and defective calcium handling. In 3D human engineered cardiac tissues (hECTs), a blunted lusitropic response to β-adrenergic stimulation was observed with R9C PLN. hiPSC-CMs harboring the R9C PLN mutation showed activation of a hypertrophic phenotype, as evidenced by expression of hypertrophic markers and increased cell size and capacitance of cardiomyocytes...
May 9, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29743563/cell-therapy-trials-for-heart-regeneration-lessons-learned-and-future-directions
#2
REVIEW
Philippe Menasché
The effects of cell therapy on heart regeneration in patients with chronic cardiomyopathy have been assessed in several clinical trials. These trials can be categorized as those using noncardiac stem cells, including mesenchymal stem cells, and those using cardiac-committed cells, including KIT+ cardiac stem cells, cardiosphere-derived cells, and cardiovascular progenitor cells derived from embryonic stem cells. Although the safety of cell therapies has been consistently reported, their efficacy remains more elusive...
May 9, 2018: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29735591/the-alchemist-s-nightmare-might-mesenchymal-stem-cells-that-are-recruited-to-repair-the-injured-heart-be-transformed-into-fibroblasts-rather-than-cardiomyocytes
#3
REVIEW
Milton Packer
The injection of mesenchymal stem cells into the injured myocardium to induce cardiac regeneration has yielded disappointing results, conceivably because cells with cardioreparative potential must be supplied for long periods of time to produce a salutary effect. Accordingly, investigators have devised ways of directing such cells to the heart on an ongoing basis: by enhancing the action of endogenous peptides that function as cardiac homing signals (eg, stromal cell-derived factor-1). Stromal cell-derived factor-1 is released during acute cardiac injury and heart failure, but it has a short half-life because of degradation by dipeptidyl peptidase-4...
May 8, 2018: Circulation
https://www.readbyqxmd.com/read/29700121/genetic-lineage-tracing-of-non-myocyte-population-by-dual-recombinases
#4
Yan Li, Lingjuan He, Xiuzhen Huang, Shirin Issa Bhaloo, Huan Zhao, Shaohua Zhang, Wenjuan Pu, Xueying Tian, Yi Li, Qiaozhen Liu, Wei Yu, Libo Zhang, Xiuxiu Liu, Kuo Liu, Juan Tang, Hui Zhang, Dongqing Cai, Ralf H Adams, Qingbo Xu, Kathy O Lui, Bin Zhou
Background -Whether the adult mammalian heart harbors cardiac stem cells (CSCs) for regeneration of cardiomyocytes is an important yet contentious topic in the field of cardiovascular regeneration. The putative myocyte stem cell populations recognized without specific cell markers such as the cardiosphere-derived cells or with markers such as Sca1+ , Bmi1+ , Isl1+ or Abcg2+ CSCs have been reported. Moreover, it remains unclear whether putative CSCs with unknown or unidentified markers exist and give rise to de novo cardiomyocytes in the adult heart...
April 26, 2018: Circulation
https://www.readbyqxmd.com/read/29696148/using-acellular-bioactive-extracellular-matrix-scaffolds-to-enhance-endogenous-cardiac-repair
#5
Daniyil A Svystonyuk, Holly E M Mewhort, Paul W M Fedak
An inability to recover lost cardiac muscle following acute ischemic injury remains the biggest shortcoming of current therapies to prevent heart failure. As compared to standard medical and surgical treatments, tissue engineering strategies offer the promise of improved heart function by inducing regeneration of functional heart muscle. Tissue engineering approaches that use stem cells and genetic manipulation have shown promise in preclinical studies but have also been challenged by numerous critical barriers preventing effective clinical translational...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29665002/three-dimensional-collagenous-niche-and-azacytidine-selectively-promote-time-dependent-cardiomyogenesis-from-human-bone-marrow-derived-msc-spheroids
#6
Jyotsna Joshi, Gautam Mahajan, Chandrasekhar R Kothapalli
Endogenous adult cardiac regenerative machinery is not capable of replacing the lost cells following myocardial infarction, often leading to permanent alterations in structure-function-mechanical properties. Regenerative therapies based on delivering autologous stem cells within an appropriate 3D milieu could meet such demand, by enabling homing and directed differentiation of the transplanted cells into lost specialized cell populations. Since type I collagen is the predominant cardiac tissue matrix protein, we here optimized the 3D niche which could promote time-dependent evolution of cardiomyogenesis from human bone marrow-derived mesenchymal stem cells (BM-MSC)...
April 17, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29660269/deterministic-encapsulation-of-human-cardiac-stem-cells-in-variable-composition-nanoporous-gel-cocoons-to-enhance-therapeutic-repair-of-injured-myocardium
#7
Pushpinder Kanda, Emilio I Alarcon, Tanya Yeuchyk, Sadrine Parent, Robert A de Kemp, Fabio Variola, David Courtman, Duncan J Stewart, Darryl R Davis
Although cocooning explant-derived cardiac stem cells in protective nanogels prior to intramyocardial injection boosts long-term cell retention, the number of EDCs that finally engraft is trivial and unlikely to account for salutary effects on myocardial function and scar size. As such, we investigated the effect of varying the nanogel content within micro-capsules to alter the physical properties of cocoons without influencing cocoon dimensions. Increasing nanogel concentration enhanced cell migration and viability while improving cell-mediated repair of injured myocardium...
April 16, 2018: ACS Nano
https://www.readbyqxmd.com/read/29625115/administration-of-placenta-derived-mesenchymal-stem-cells-counteracts-a-delayed-anergic-state-following-a-transient-induction-of-endogenous-neurogenesis-activity-after-global-cerebral-ischemia
#8
A Ra Kho, Ok Joon Kim, Jeong Hyun Jeong, Ji Min Yu, Hye Sun Kim, Bo Young Choi, Sang Won Suh, Tae Nyoung Chung
BACKGROUND: Global cerebral ischemia (GCI) is a major obstacle for cardiac arrest survival. Recent studies have suggested the possibility of mesenchymal stem cell (MSC) as a novel therapeutic option for GCI, but these results were limited to the neuroprotective effects of MSCs. Therefore, we aimed to investigate specific characteristics of neurogenesis after transient GCI, and to assess the effect of MSC on these characteristics. METHODS: Adult male Sprague-Dawley rats were subjected to 7 minutes of transient GCI and randomized into 7 groups: baseline, MSC, and control administered groups, to be analyzed at 2, 3, and 4 weeks after GCI, respectively...
April 3, 2018: Brain Research
https://www.readbyqxmd.com/read/29574723/calcium-dependent-potassium-channels-control-proliferation-of-cardiac-progenitor-cells-and-bone-marrow-derived-mesenchymal-stem-cells
#9
Patrick Vigneault, Patrice Naud, Xiaoyan Qi, Jiening Xiao, Louis Villeneuve, Darryl R Davis, Stanley Nattel
Endogenous c-Kit+ cardiac progenitor cells (eCPCs) and bone marrow (BM)-derived mesenchymal stem cells (MSCs) are being developed for cardiac regenerative therapy, but a better understanding of their physiology is needed. Here, we addressed the unknown functional role of ion-channels in freshly-isolated eCPCs and expanded BM-MSCs using patch-clamp, microfluorometry and confocal microscopy. Isolated c-Kit+ eCPCs were purified from dog hearts by immunomagnetic selection. Ion-currents were barely detectable in freshly-isolated c-Kit+ eCPCs with intracellular calcium (Ca2+ i ) buffered...
March 25, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29542684/exosomes-from-suxiao-jiuxin-pill-treated-cardiac-mesenchymal-stem-cells-decrease-h3k27-demethylase-utx-expression-in-mouse-cardiomyocytes-in-vitro
#10
Xiao-Fen Ruan, Yong-Jun Li, Cheng-Wei Ju, Yan Shen, Wei Lei, Can Chen, Yang Li, Hong Yu, Yu-Tao Liu, Il-Man Kim, Xiao-Long Wang, Neal L Weintraub, Yao-Liang Tang
Suxiao Jiuxin Pill (SJP) is a traditional Chinese medicine for the treatment of acute coronary syndrome in China, which contains two principal components, tetramethylpyrazine (TMP) and borneol (BOR). Thus far, however, the molecular mechanisms underlying the beneficial effects of SJP on the cardiac microenvironment are unknown. Cardiac mesenchymal stem cells (C-MSCs) communicate with cardiomyocytes (CMs) through the release of microvesicles (exosomes) to restore cardiac homeostasis and elicit repair, in part through epigenetic regulatory mechanisms...
March 15, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29542682/suxiao-jiuxin-pill-promotes-exosome-secretion-from-mouse-cardiac-mesenchymal-stem-cells-in-vitro
#11
Xiao-Fen Ruan, Cheng-Wei Ju, Yan Shen, Yu-Tao Liu, Il-Man Kim, Hong Yu, Neal Weintraub, Xiao-Long Wang, Yao-Liang Tang
Cardiac mesenchymal stem cells (C-MSCs) are endogenous cardiac stromal cells that play a role in heart repair after injury. C-MSC-derived exosomes (Exo) have shown protective effects against apoptosis induced by acute myocardial ischemia/reperfusion. Suxiao Jiuxin pill (SJP) is a traditional Chinese medicine (TCM) formula used in China for the treatment of acute myocardial ischemia, which contains tetramethylpyrazine (TMP) and borneol (BOR) as major components. In this study, we investigated whether SJP treatment affected exosome release from C-MSCs in vitro...
March 15, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29475983/s1p-s1pr2-axis-mediates-homing-of-muse-cells-into-damaged-heart-for-long-lasting-tissue-repair-and-functional-recovery-after-acute-myocardial-infarction
#12
Yoshihisa Yamada, Shohei Wakao, Yoshihiro Kushida, Shingo Minatoguchi, Atsushi Mikami, Kenshi Higashi, Shinya Baba, Taeko Shigemoto, Yasumasa Kuroda, Hiromitsu Kanamori, Mohamad Amin, Masanori Kawasaki, Kazuhiko Nishigaki, Masato Taoka, Toshiaki Isobe, Chisako Muramatsu, Mari Dezawa, Shinya Minatoguchi
RATIONALE: Multilineage-differentiating stress enduring (Muse) cells, pluripotent marker stage-specific embryonic antigen-3+ cells, are nontumorigenic endogenous pluripotent-like stem cells obtainable from various tissues including the bone marrow. Their therapeutic efficiency has not been validated in acute myocardial infarction. OBJECTIVE: The main objective of this study is to clarify the efficiency of intravenously infused rabbit autograft, allograft, and xenograft (human) bone marrow-Muse cells in a rabbit acute myocardial infarction model and their mechanisms of tissue repair...
April 13, 2018: Circulation Research
https://www.readbyqxmd.com/read/29399560/functional-relevance-of-macrophage-mediated-inflammation-to-cardiac-regeneration
#13
REVIEW
Yong Sook Kim, Youngkeun Ahn
Cardiovascular disease remains the leading cause of death worldwide and regenerative medicine is a promising therapeutic option for this disease. We have developed various techniques to attenuate the cardiac remodeling and to regenerate cardiovascular systems via stem cell application. Besides cell therapy, we are interested in the modulation of pathological inflammation mediated by macrophages in the damaged heart tissue to arouse endogenous reparative responses with biocompatible small molecules. Certainly, current understanding of mechanisms of tissue regeneration will lead to the development of innovative regenerative medicine for cardiovascular disease...
January 2018: Chonnam Medical Journal
https://www.readbyqxmd.com/read/29350399/biological-functions-of-elabela-a-novel-endogenous-ligand-of-apj-receptor
#14
REVIEW
Jin Xu, Linxi Chen, Zhisheng Jiang, Lanfang Li
The G protein-coupled receptor APJ and its cognate ligand, apelin, are widely expressed throughout human body. They are implicated in different key physiological processes such as angiogenesis, cardiovascular functions, fluid homeostasis, and energy metabolism regulation. Recently, a new endogenous peptidic ligand of APJ, named Elabela, has been identified and shown to play a crucial role in embryonic development. In addition, increasing evidences show that Elabela is also intimate associated with a large number of physiological processes in adulthood...
January 19, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29348441/sdf1-gradient-associates-with-the-distribution-of-c-kit-cardiac-cells-in-the-heart
#15
Outi Renko, Anna-Maria Tolonen, Jaana Rysä, Johanna Magga, Erja Mustonen, Heikki Ruskoaho, Raisa Serpi
Identification of the adult cardiac stem cells (CSCs) has offered new therapeutic possibilities for treating ischemic myocardium. CSCs positive for the cell surface antigen c-Kit are known as the primary source for cardiac regeneration. Accumulating evidence shows that chemokines play important roles in stem cell homing. Here we investigated molecular targets to be utilized in modulating the mobility of endogenous CSCs. In a four week follow-up after experimental acute myocardial infarction (AMI) with ligation of the left anterior descending (LAD) coronary artery of Sprague-Dawley rats c-Kit+ CSCs redistributed in the heart...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29347847/combining-cell-and-gene-therapy-to-advance-cardiac-regeneration
#16
Pina Marotta, Eleonora Cianflone, Iolanda Aquila, Carla Vicinanza, Mariangela Scalise, Fabiola Marino, Teresa Mancuso, Michele Torella, Ciro Indolfi, Daniele Torella
The characterization of multipotent endogenous cardiac stem cells (eCSCs) and the breakthroughs of somatic cell reprogramming to boost cardiomyocyte replacement have fostered the prospect of achieving functional heart repair/regeneration. Areas covered: Allogeneic CSC therapy through its paracrine stimulation of the endogenous resident reparative/regenerative process produces functional meaningful myocardial regeneration in pre-clinical porcine myocardial infarction models and is currently tested in the first-in-man human trial...
April 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29284167/regenerative-medicine-cardiac-cell-therapy-adult-somatic-progenitor-cells
#17
Timo Z Nazari-Shafti, Jörg Kempfert, Volkmar Falk, Wilhelm Röll, Christof Stamm
Preclinical data suggested that somatic stem or progenitor cells derived induce and/or support endogenous repair mechanisms of the myocardium. Such cell populations were clearly shown to promote neovascularization in postischemic tissue, and some evidence also indicated transdifferentiation into cardiomyocytes. In the clinical setting, however, many attempts to regenerate damaged myocardium with a variety of autologous and allogeneic somatic progenitors have failed to generate the expected therapeutic efficacy...
January 2018: Thoracic and Cardiovascular Surgeon
https://www.readbyqxmd.com/read/29281682/overexpression-of-map3k7-activates-sinoatrial-node-like-differentiation-in-mouse-es-derived-cardiomyocytes
#18
Kemar Brown, Stephanie Legros, Francis A Ortega, Yunkai Dai, Michael Xavier Doss, David J Christini, Richard B Robinson, Ann C Foley
In vivo, cardiomyocytes comprise a heterogeneous population of contractile cells defined by unique electrophysiologies, molecular markers and morphologies. The mechanisms directing myocardial cells to specific sub-lineages remain poorly understood. Here we report that overexpression of TGFβ-Activated Kinase (TAK1/Map3k7) in mouse embryonic stem (ES) cells faithfully directs myocardial differentiation of embryoid body (EB)-derived cardiac cells toward the sinoatrial node (SAN) lineage. Most cardiac cells in Map3k7-overexpressing EBs adopt markers, cellular morphologies, and electrophysiological behaviors characteristic of the SAN...
2017: PloS One
https://www.readbyqxmd.com/read/29207135/bfgf-promotes-sca%C3%A2-1-cardiac-stem-cell-migration-through-activation-of-the-pi3k-akt-pathway
#19
Lin Ling, Shaohua Gu, Yan Cheng, Liucheng Ding
Cardiac stem cells (CSCs) are important for improving cardiac function following myocardial infarction, with CSC migration to infarcted or ischemic myocardium important for cardiac regeneration. Strategies to improve cell migration may improve the efficiency of myocardial regeneration. Basic fibroblast growth factor (bFGF) is an essential molecule in cell migration, but the endogenous bFGF level is too low to be effective. The effect of exogenously delivered bFGF on CSC migration was observed in vitro and in vivo in the present study...
February 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29206745/cardiosphere-derived-cells-and-ischemic-heart-failure
#20
Carmel Ashur, William H Frishman
After a myocardial infarction, heart tissue becomes irreversibly damaged, leading to scar formation and inevitably ischemic heart failure. Of the many available interventions after a myocardial infarction, such as percutaneous intervention or pharmacological optimization, none can reverse the ischemic insult on the heart and restore cardiac function. Thus, the only available cure for patients with scarred myocardium is allogeneic heart transplantation, which comes with extensive costs, risks, and complications...
January 2018: Cardiology in Review
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