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myoblast transplantation

Maria Siemionow, Joanna Cwykiel, Ahlke Heydemann, Jesus Garcia, Enza Marchese, Krzysztof Siemionow, Erzsebet Szilagyi
Duchenne Muscular Dystrophy (DMD) is a progressive and lethal disease caused by mutations of the dystrophin gene. Currently no cure exists. Stem cell therapies targeting DMD are challenged by limited engraftment and rejection despite the use of immunosuppression. There is an urgent need to introduce new stem cell-based therapies that exhibit low allogenic profiles and improved cell engraftment. In this proof-of-concept study, we develop and test a new human stem cell-based approach to increase engraftment, limit rejection, and restore dystrophin expression in the mdx/scid mouse model of DMD...
March 15, 2018: Stem Cell Reviews
Daniel Skuk, Jacques P Tremblay
Background: Transplantation of myogenic cells has potential applications in the treatment of muscle pathologies. Excluding purely autologous cell transplantation, graft viability depends on an adequate control of acute rejection (AR). To contribute in understanding AR in this context, we analyzed whether de novo circulating antibodies against donor's cells are detected during induced AR of graft-derived myofibers in nonhuman primates. Methods: We allotransplanted satellite cell-derived myoblasts in macaques immunosuppressed with tacrolimus...
December 2017: Transplantation Direct
Kamil R Wierzbinski, Tomasz Szymanski, Natalia Rozwadowska, Jakub D Rybka, Agnieszka Zimna, Tomasz Zalewski, Karolina Nowicka-Bauer, Agnieszka Malcher, Magdalena Nowaczyk, Michal Krupinski, Michal Fiedorowicz, Piotr Bogorodzki, Pawel Grieb, Michal Giersig, Maciej K Kurpisz
Myocardial infarction (MI) is one of the most frequent causes of death in industrialized countries. Stem cells therapy seems to be very promising for regenerative medicine. Skeletal myoblasts transplantation into postinfarction scar has been shown to be effective in the failing heart but shows limitations such, e.g. cell retention and survival. We synthesized and investigated superparamagnetic iron oxide nanoparticles (SPIONs) as an agent for direct cell labeling, which can be used for stem cells imaging. High quality, monodisperse and biocompatible DMSA-coated SPIONs were obtained with thermal decomposition and subsequent ligand exchange reaction...
February 27, 2018: Scientific Reports
Christophe Praud, Karine Vauchez, Pascal Zongo, Jean-Thomas Vilquin
Cell transplantation has been challenged in several clinical indications of genetic or acquired muscular diseases, but therapeutic success were mitigated. To understand and improve the yields of tissue regeneration, we aimed at modelling the fate of CD56-positive human myoblasts after transplantation. Using immunodeficient severe combined immunodeficiency (SCID) mice as recipients, we assessed the survival, integration and satellite cell niche occupancy of human myoblasts by a triple immunohistochemical labelling of laminin, dystrophin and human lamin A/C...
February 16, 2018: Experimental Cell Research
Hailey A Houson, Gregory N Nkepang, Andria F Hedrick, Vibhudutta Awasthi
Positron emission tomography (PET) of myocardial infarction (MI) by infarct avid imaging has the potential to reduce the time to diagnosis and improve diagnostic accuracy. The objective of this work was to synthesize 18 F-labeled glucaric acid (FGA) for PET imaging of isoproterenol-induced cardiomyopathy in a rat model. METHODS: We synthesized 18 F-FGA by controlled oxidation of 18 F-fluorodeoxy glucose (FDG), mediated by 4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) in presence of NaBr and NaOCl in highly-buffered reaction conditions...
December 27, 2017: Nuclear Medicine and Biology
Chiara Sassoli, Larissa Vallone, Alessia Tani, Flaminia Chellini, Daniele Nosi, Sandra Zecchi-Orlandini
Satellite cell-mediated skeletal muscle repair/regeneration is compromised in cases of extended damage. Bone marrow mesenchymal stromal cells (BM-MSCs) hold promise for muscle healing but some criticisms hamper their clinical application, including the need to avoid animal serum contamination for expansion and the scarce survival after transplant. In this context, platelet-rich plasma (PRP) could offer advantages. Here, we compare the effects of PRP or standard culture media on C2C12 myoblast, satellite cell and BM-MSC viability, survival, proliferation and myogenic differentiation and evaluate PRP/BM-MSC combination effects in promoting myogenic differentiation...
February 5, 2018: Cell and Tissue Research
Lucas Andreo, Raquel A Mesquita-Ferrari, Beatriz G Ribeiro, Adriana Benitte, Tatiane de Fátima Nogueira, Cristiane M França, Daniela de Fátima Teixeira da Silva, Sandra K Bussadori, Kristianne P S Fernandes, Fernanda I Corrêa, João C F Corrêa
OBJECTIVE: The aim of the present study was to evaluate the effects of myoblast inoculation in combination with photobiomodulation therapy (PBMT) on skeletal muscle tissue following injury. MATERIALS AND METHODS: Sixty-five Wistar rats were divided into five groups: Control-animals not submitted to any procedure; Injury-cryoinjury of the tibialis anterior muscle; HBSS-animals submitted to cryoinjury and intramuscular Hank's Balanced Salt Solution; Injury + Cells-animals submitted to cryoinjury, followed by myogenic precursor cells (C2C12) transplantation; Injury + Cells + LLLT-animals submitted to cryoinjury, followed by myogenic precursor cells (C2C12) transplantation and PBMT (780 nm, 40 mW, 3...
February 5, 2018: Lasers in Surgery and Medicine
Koji Nagahama, Naho Oyama, Kimika Ono, Atsushi Hotta, Keiko Kawauchi, Takahito Nishikata
Injectable hydrogels are biomaterials that have the potential to provide scaffolds to cells for in situ tissue regeneration with a minimally invasive implantation procedure. The success of in vivo tissue engineering utilizing injectable gels depends on providing cells with appropriate scaffolds that present an instructive extracellular microenvironment, which strongly influences the survival, proliferation, organization, and function of cells encapsulated within gels. One of the most important abilities of injectable gels to achieve this function is to adsorb and retain a wide variety of requisite bioactive molecules including nutrients, extracellular matrices, and growth/differentiation factors within gels...
January 30, 2018: Biomaterials Science
Satoshi Kainuma, Kiyokazu Nakajima, Shigeru Miyagawa, Satsuki Fukushima, Atsuhiro Saito, Akima Harada, Masashi Hirota, Yasuhiro Miyazaki, Noriyoshi Sawabata, Tadashi Watabe, Hiroshi Watabe, Koichi Toda, Jun Hatazawa, Meinoshin Okumura, Yoshiki Sawa
OBJECTIVES: We previously reported that cell sheet transplantation combined with an omentopexy (OP) procedure is more effective for repairing heart damage when compared with cell sheet transplantation alone. However, a simultaneous (conventional) laparotomy as part of the OP may adversely affect the general condition of critically ill heart failure patients who would otherwise benefit from cell sheet transplantation, which is a paradox to be reconciled before this treatment can be applied in a clinical setting...
January 18, 2018: Interactive Cardiovascular and Thoracic Surgery
Daniel Skuk, Jacques P Tremblay
We studied in macaques the evolution of the intramuscular transplantation of muscle precursor cells between the time of administration and the time at which the graft is considered stable. Satellite cell-derived myoblasts labeled with ß-galactosidase were transplanted into 1 cm3 muscle regions following cell culture and transplantation protocols similar to our last clinical trials. These regions were biopsied 1 h, 1, 3, 7 d, and 3 wk later and analyzed by histology. We observed that the cell suspension leaks from the muscle bundles during injection toward the epimysium and perimysium, where most cells accumulate after transplantation...
November 2017: Cell Transplantation
M Siemionow, J Cwykiel, A Heydemann, J Garcia-Martinez, K Siemionow, E Szilagyi
Over the past decade different stem cell (SC) based approaches were tested to treat Duchenne Muscular Dystrophy (DMD), a lethal X-linked disorder caused by mutations in dystrophin gene. Despite research efforts, there is no curative therapy for DMD. Allogeneic SC therapies aim to restore dystrophin in the affected muscles; however, they are challenged by rejection and limited engraftment. Thus, there is a need to develop new more efficacious SC therapies. Chimeric Cells (CC), created via ex vivo fusion of donor and recipient cells, represent a promising therapeutic option for tissue regeneration and Vascularized Composite Allotransplantation (VCA) due to tolerogenic properties that eliminate the need for lifelong immunosuppression...
January 5, 2018: Stem Cell Reviews
Lise K Hansen, Henrik D Schrøder, Lars Lund, Karthikeyan Rajagopal, Vrisha Maduri, Jeeva Sellathurai
BACKGROUND: Transplanting myogenic cells and scaffolds for tissue engineering in skeletal muscle have shown inconsistent results. One of the limiting factors is neovascularization at the recipient site. Low intensity shockwave therapy (Li-SWT) has been linked to increased tissue regeneration and vascularization, both integral to survival and integration of transplanted cells. This study was conducted to demonstrate the response of myoblasts and skeletal muscle to Li-SWT. METHOD: Primary isolated human myoblasts and explants were treated with low intensity shockwaves and subsequently cell viability, proliferation and differentiation were tested...
December 29, 2017: BMC Musculoskeletal Disorders
Fukuko Horio, Hidetoshi Sakurai, Yutaka Ohsawa, Shiho Nakano, Makoto Matsukura, Isao Fujii
Previously, we reported that MyoD, a master gene for myogenic cells, could efficiently convert primary skin fibroblasts into myoblasts and myotubes, thereby effecting direct reprogramming. In this study, we further demonstrated that MyoD-expressing primary fibroblasts displayed rapid movement in culture, with a movement velocity that was significantly faster, almost four times, than mouse primary myoblasts. MyoD-transduced cells obtained the characteristics of Ca2 + release and electrically-stimulated contraction, which was comparable to C2C12 myotubes, suggesting that the essential features of muscle were observed in the transduced cells...
March 2017: ENeurologicalSci
Sara Benedetti, Narumi Uno, Hidetoshi Hoshiya, Martina Ragazzi, Giulia Ferrari, Yasuhiro Kazuki, Louise Anne Moyle, Rossana Tonlorenzi, Angelo Lombardo, Soraya Chaouch, Vincent Mouly, Marc Moore, Linda Popplewell, Kanako Kazuki, Motonobu Katoh, Luigi Naldini, George Dickson, Graziella Messina, Mitsuo Oshimura, Giulio Cossu, Francesco Saverio Tedesco
Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combination of large-capacity vectors, such as human artificial chromosomes (HACs), with stem/progenitor cells may overcome this limitation. We previously reported amelioration of the dystrophic phenotype in mice transplanted with murine muscle progenitors containing a HAC with the entire dystrophin locus (DYS-HAC)...
December 14, 2017: EMBO Molecular Medicine
Jiro Abe, Yuma Yamada, Atsuhito Takeda, Hideyoshi Harashima
It has been reported that transplanting native cells would lack efficiency without producing artificial cell-tissue, due to the exaggerated oxidative stress in doxorubicin-induced cardiomyopathy. We attempted to activate cardiac progenitor cells (CPCs) by delivering resveratrol to mitochondria using a mitochondrial drug delivery system (MITO-Porter system). We first evaluated the viability of H9c2 cells (a cardio myoblast cell line) after doxorubicin treatment, where H9c2 cells were co-cultured with or without the mitochondria activated CPCs (referred to herein as MITO cell)...
January 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Jung-Won Choi, Sunhye Shin, Chang Youn Lee, Jiyun Lee, Hyang-Hee Seo, Soyeon Lim, Seahyoung Lee, Il-Kwon Kim, Hoon-Bum Lee, Sang Woo Kim, Ki-Chul Hwang
BACKGROUND/AIMS: Stromal vascular fraction (SVF) cells are a mixed cell population, and their regenerative capacity has been validated in various therapeutic models. The purpose of this study was to investigate the regenerative mechanisms utilized by implanted SVF cells. Using an in vitro co-culture system, we sought to determine whether SVF implantation into impaired tissue affects endogenous mesenchymal stem cell (MSC) differentiation; MSCs can differentiate into a variety of cell types, and they have a strong regenerative capacity despite their low numbers in impaired tissue...
November 3, 2017: Cellular Physiology and Biochemistry
Alberto Perez-Bouza, Stefano Di Santo, Stefanie Seiler, Morten Meyer, Lukas Andereggen, Alexander Huber, Raphael Guzman, Hans R Widmer
Transplantation of fetal ventral mesencephalic (VM) neurons for Parkinson's disease (PD) is limited by poor survival and suboptimal integration of grafted tissue into the host brain. In a 6-hydroxydopamine rat model of PD, we investigated the feasibility of simultaneous transplantation of rat fetal VM tissue and polymer-encapsulated C2C12 myoblasts genetically modified to produce glial cell line-derived neurotrophic factor (GDNF) or mock-transfected myoblasts on graft function. Amphetamine-induced rotations were assessed prior to transplantation and 2, 4, 6 and 9 wk posttransplantation...
September 2017: Cell Transplantation
Mariela Natacha González, Wallace de Mello, Gillian S Butler-Browne, Suse Dayse Silva-Barbosa, Vincent Mouly, Wilson Savino, Ingo Riederer
BACKGROUND: The hepatocyte growth factor (HGF) is required for the activation of muscle progenitor cells called satellite cells (SC), plays a role in the migration of proliferating SC (myoblasts), and is present as a soluble factor during muscle regeneration, along with extracellular matrix (ECM) molecules. In this study, we aimed at determining whether HGF is able to interact with ECM proteins, particularly laminin 111 and fibronectin, and to modulate human myoblast migration. METHODS: We evaluated the expression of the HGF-receptor c-Met, laminin, and fibronectin receptors by immunoblotting, flow cytometry, or immunofluorescence and used Transwell assays to analyze myoblast migration on laminin 111 and fibronectin in the absence or presence of HGF...
October 10, 2017: Skeletal Muscle
Bo Wang, Likui Zhang, Hao Cao, Junqi Yang, Manya Wu, Yali Ma, Huimin Fan, Zhenzhen Zhan, Zhongmin Liu
Myocardial infarction (MI) is a highly prevalent cardiac emergency, which results in adverse cardiac remodeling and then exacerbates progressive heart failure. Inflammatory responses in cardiac tissue after MI is necessary for myocardium repair and wound healing. However, the excessive inflammation is also a key component of subsequent heart failure pathology. Myoblast transplantation after MI have been fulfilled attractive effects on cardiac repair, but the complications of transplantation and the underlying mechanisms have not been fully elucidated...
September 15, 2017: Oncotarget
Yan Liu, Michael J Conboy, Melod Mehdipour, Yutong Liu, Thanhtra P Tran, Aaron Blotnick, Prasanna Rajan, Thalie Cavalcante Santos, Irina M Conboy
Studies of heterochronic parabiosis demonstrated that with age, the composition of the circulatory milieu changes in ways that broadly inhibit tissue regenerative capacity. In addition, local tissue niches have age-specific influences on their resident stem cells. Here we use bio-orthogonal proteome labeling for detecting in vivo proteins present only in transplanted myoblasts, but not in host tissue, and proteins exclusive to one young mouse and transferred during parabiosis to its old partner. We use a transgenic mouse strain that ubiquitously expresses a modified tRNA methionine synthase, metRS, which preferentially incorporates the methionine surrogate azido-nor-leucine (ANL) into newly generated proteins...
September 21, 2017: Nature Communications
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