196,077 research outputs found
Unconventional Players on the Striated Muscle Field: MicroRNAs, Signaling Pathways and Epigenetic Regulators
No full textStriated muscle regeneration holds an intrinsic complexity governed by many orchestrated events. When the fine balance of regulatory machineries is under strain, the homeostatic conditions are lost and degeneration starts to occur. This is the case for inherited and acquired diseases of both cardiac and skeletal muscles. A wide range of factors is currently under scrutiny for better understanding the details underlying de-/re-generation processes, of both genetic and non-genetic nature. This review focuses on three classes of non-genetic factors regulating striated muscle regeneration, i.e. microRNAs, signaling pathways and epigenetic regulators
Pluripotent stem cell derivation and differentiation toward cardiac muscle: novel techniques and advances in patent literature.
No full textPluripotent stem cells hold unprecedented potential for regenerative medicine, disease modeling and drug screening. Embryonic stem cells (ESCs), standard model for pluripotency studies, have been recently flanked by induced pluripotent stem cells (iPSCs). iPSCs are obtained from somatic cells via epigenetic and transcriptional reprogramming, overcoming ESC-related ethical issues and enabling the possibility of donor-matching pluripotent cell lines. Since the European Court of Justice banned patents involving embryo disaggregation to generate human ESCs, iPSCs can now fuel the willingness of European companies to invest in treatments based on stem cells. Moreover, iPSCs share many unique features of ESCs, such as unlimited self-renewal potential and broad differentiation capability, even though iPSCs seem more susceptible to genomic instability and display epigenetic biases as compared to ESCs. Both ESCs and iPSCs have been intensely investigated for cardiomyocyte production and cardiac muscle regeneration, both in human and animal models. In vitro and in vivo studies are continuously expanding and refining this field via genetic manipulation and cell conditioning, trying to achieve standard and reproducible products, eligible for clinical and biopharmaceutical scopes. This review focuses on the recently growing body of patents, concerning technical advances in production, expansion and cardiac differentiation of ESCs and iPSCs
Cell therapy strategies and improvements for muscular dystrophy
No full textUnderstanding stem cell commitment and differentiation is a critical step towards clinical translation of cell therapies. In past few years, several cell types have been characterized and transplanted in animal models for different diseased tissues, eligible for a cell-mediated regeneration. Skeletal muscle damage is a challenge for cell- and gene-based therapeutical approaches, given the unique architecture of the tissue and the clinical relevance of acute damages or dystrophies. In this review, we will consider the regenerative potential of embryonic and somatic stem cells and the outcomes achieved on their transplantation into animal models for muscular dystrophy or acute muscle impairment
Cell therapy strategies and improvements for muscular dystrophy.
No full textUnderstanding stem cell commitment and differentiation is a critical step towards clinical translation of cell therapies. In past few years, several cell types have been characterized and transplanted in animal models for different diseased tissues, eligible for a cell-mediated regeneration. Skeletal muscle damage is a challenge for cell- and gene-based therapeutical approaches, given the unique architecture of the tissue and the clinical relevance of acute damages or dystrophies. In this review, we will consider the regenerative potential of embryonic and somatic stem cells and the outcomes achieved on their transplantation into animal models for muscular dystrophy or acute muscle impairment.Cell Death and Differentiation advance online publication, 30 October 2009; doi:10.1038/cdd.2009.160.sponsorship: We thank Paolo Luban for his support. We are particularly grateful to Guido Tettamanti and Giulio Cossu for critical reading of the paper and for helpful comments, and Shea Carter for the ms proofreading service. This work was supported by FWO Odysseus Program n.G.0907.08; Wicka Funds n.zkb8720, University of Minnesota US; the Italian Ministry of University and Scientific Research (grant n. 2005067555_003, COFIN 2006-08), the Muscular Dystrophy Association, Association Francoise contre les Myopathies, CARIPLO Funds 2007-5639 and 2008-2005. (FWO Odysseus|n.G.0907.08, Wicka Funds|n.zkb8720, University of Minnesota US, Italian Ministry of University and Scientific Research|2005067555_003, Muscular Dystrophy Association, Association Francoise contre les Myopathies, CARIPLO|2007-5639, CARIPLO|2008-2005)status: Publishe
Notch signaling regulates myogenic regenerative capacity of murine and human mesoangioblasts
No full textSomatic stem cells hold attractive potential for the treatment of muscular dystrophies (MDs). Mesoangioblasts (MABs) constitute a myogenic subset of muscle pericytes and have been shown to efficiently regenerate dystrophic muscles in mice and dogs. In addition, HLA-matched MABs are currently being tested in a phase 1 clinical study on Duchenne MD patients (EudraCT #2011-000176-33). Many reports indicate that the Notch pathway regulates muscle regeneration and satellite cell commitment. However, little is known about Notch-mediated effects on other resident myogenic cells. To possibly potentiate MAB-driven regeneration in vivo, we asked whether Notch signaling played a pivotal role in regulating MAB myogenic capacity. Through different approaches of loss- and gain-of-function in murine and human MABs, we determined that the interplay between Delta-like ligand 1 (Dll1)-activated Notch1 and Mef2C supports MAB commitment in vitro and ameliorates engraftment and functional outcome after intra-arterial delivery in dystrophic mice. Furthermore, using a transgenic mouse model of conditional Dll1 deletion, we demonstrated that Dll1 ablation, either on the injected cells, or on the receiving muscle fibers, impairs MAB regenerative potential. Our data corroborate the perspective of advanced combinations of cell therapy and signaling tuning to enhance therapeutic efficaciousness of somatic stem cells
Mouse and human mesoangioblasts: isolation and characterization from adult skeletal muscles
No full textMesoangioblasts (MABS) are mesoderm-derived stem cells, associated with small vessels and originally described in the mouse embryonic dorsal aorta. Similar though not identical cells have been later identified and characterized from postnatal small vessels of skeletal muscle and heart. They have in common the expression of pericyte markers, the anatomical location, the ability to self-renew in culture, and to differentiate into various types of mesodermal lineages upon proper culture conditions. Currently, the developmental origin of MABs and the relationship with other muscle stem cells are not understood in detail and are the subject of active research. This chapter provides an outline of the latest techniques for isolation and characterization of adult MABs from human and mouse skeletal muscles
Stem cell therapy in muscular dystrophies Stem cell and small RNAs as tools for basic science and regenerative medicine
No full textCardiac dystrophic mesoangioblasts molecular characterization of in vitro and in vivo differentiation
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