scholarly journals Adipose-derived Stem/Stromal Cells on Electrospun Fibrin Microfiber Bundles Enable Moderate Muscle Reconstruction in a Volumetric Muscle Loss Model

2018 ◽  
Vol 27 (11) ◽  
pp. 1644-1656 ◽  
Author(s):  
Jordana Gilbert-Honick ◽  
Brian Ginn ◽  
Yuanfan Zhang ◽  
Sara Salehi ◽  
Kathryn R. Wagner ◽  
...  
Keyword(s):  
Treatment Options ◽  
Donor Site ◽  
Donor Site Morbidity ◽  
Current Treatment ◽  
Muscle Loss ◽  
Post Transplantation ◽  
Volumetric Muscle Loss ◽  
Volume Retention

Current treatment options for volumetric muscle loss (VML) are limited due to donor site morbidity, lack of donor tissue, and insufficient functional recovery. Tissue-engineered skeletal muscle grafts offer the potential to significantly improve functional outcomes. In this study, we assessed the potential pro-myogenic effects of human adipose-derived stem cells (ASCs) seeded onto electrospun uniaxially aligned fibrin hydrogel microfiber bundles. Although both uninduced and 5-azacytidine-induced ASCs exhibited alignment, elongation, and diffuse muscle marker expression when grown on microfiber bundles for 2 months in vitro, both groups failed to fully recapitulate myotube characteristics. To assess the muscle regeneration potential of ASCs in vivo, ASC-seeded fibrin microfiber bundles were implanted in a robust murine VML defect model. Minimal fibrosis was observed surrounding implanted acellular hydrogel fibers at 2 and 4 weeks, and fibers seeded with ASCs exhibited up to 4 times higher volume retention than acellular fibers. We observed increased numbers of cells positive for the regenerating muscle marker embryonic myosin and the mature muscle marker myosin heavy chain in ASC-seeded fibers compared with acellular fibers at 1 and 3 months post-transplantation. Regenerating muscle cells were closely associated with ASC-derived cells and in some cases had potentially fused with them. These findings demonstrate that despite failing to undergo myogenesis in vitro, ASCs combined with electrospun fibrin microfibers moderately increased muscle reconstruction in vivo compared with acellular fibers following a severe VML defect.

Mesenchymal stem cell-derived extracellular vesicles in the failing heart: past, present, and future

2021 ◽  
Author(s):  
Catherine Karbasiafshar ◽  
Frank W. Sellke ◽  
M. Ruhul Abid
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Treatment Options ◽  
Current Treatment ◽  
Lifestyle Changes ◽  
Challenges And Opportunities ◽  
Artery Disease ◽  
New Treatment

Cardiovascular disease (CVD) is the leading cause of death globally. Current treatment options include lifestyle changes, medication, and surgical intervention. However, many patients are unsuitable candidates for surgeries due to comorbidities, diffuse coronary artery disease or advanced stages of heart failure. The search for new treatment options has recently transitioned from cell-based therapies to stem-cell derived extracellular vesicles (EVs). A number of challenges remain in the EV field, including the effect of comorbidities, characterization, and delivery, However, recent revolutionary developments and insight into the potential of 'personalizing' EV contents by bioengineering methods to alter specific signaling pathways in the ischemic myocardium hold promise. Here, we discuss the past limitations of cell-based therapies, and recent EV studies involving in vivo, in vitro, and omics, and future challenges and opportunities in EV-based treatments in CVD.

Effects of the tetrahedral framework nucleic acids on the skeletal muscle regeneration in vitro and in vivo

2020 ◽  
Vol 4 (9) ◽  
pp. 2731-2743
Author(s):  
Yang Gao ◽  
Tianxu Zhang ◽  
Junyao Zhu ◽  
Dexuan Xiao ◽  
Mei Zhang ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Muscle Loss ◽  
Degenerative Diseases ◽  
Tetrahedral Framework ◽  
Volumetric Muscle Loss ◽  
Regeneration In Vitro

The challenges associated with muscle degenerative diseases and volumetric muscle loss (VML) emphasizes the prospects of muscle tissue regeneration.

scholarly journals Matured Myofibers in Bioprinted Constructs with In Vivo Vascularization and Innervation

Gels ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. 171
Author(s):  
Catherine G. Y. Ngan ◽  
Anita Quigley ◽  
Richard J. Williams ◽  
Cathal D. O’Connell ◽  
Romane Blanchard ◽  
...  
Keyword(s):  
Neuromuscular Diseases ◽  
Structural Development ◽  
Muscle Loss ◽  
Test Drug ◽  
Scaffold Material ◽  
Volumetric Muscle Loss ◽  
Primary Mouse ◽  
First Time

For decades, the study of tissue-engineered skeletal muscle has been driven by a clinical need to treat neuromuscular diseases and volumetric muscle loss. The in vitro fabrication of muscle offers the opportunity to test drug-and cell-based therapies, to study disease processes, and to perhaps, one day, serve as a muscle graft for reconstructive surgery. This study developed a biofabrication technique to engineer muscle for research and clinical applications. A bioprinting protocol was established to deliver primary mouse myoblasts in a gelatin methacryloyl (GelMA) bioink, which was implanted in an in vivo chamber in a nude rat model. For the first time, this work demonstrated the phenomenon of myoblast migration through the bioprinted GelMA scaffold with cells spontaneously forming fibers on the surface of the material. This enabled advanced maturation and facilitated the connection between incoming vessels and nerve axons in vivo without the hindrance of a scaffold material. Immunohistochemistry revealed the hallmarks of tissue maturity with sarcomeric striations and peripherally placed nuclei in the organized bundles of muscle fibers. Such engineered muscle autografts could, with further structural development, eventually be used for surgical reconstructive purposes while the methodology presented here specifically has wide applications for in vitro and in vivo neuromuscular function and disease modelling.

scholarly journals Injections in the osteoarthritic knee: a review of current treatment options

2021 ◽  
Vol 6 (6) ◽  
pp. 501-509
Author(s):  
Gerardo Fusco ◽  
Francesco M. Gambaro ◽  
Berardo Di Matteo ◽  
Elizaveta Kon
Keyword(s):  
Platelet Rich Plasma ◽  
Symptomatic Relief ◽  
Treatment Options ◽  
Cartilage Degradation ◽  
Current Treatment ◽  
Biologic Agents ◽  
Knee Oa ◽  
Molecular Approaches

Knee osteoarthritis is a degenerative condition characterized by progressive cartilage degradation, subchondral damage, and bone remodelling. Among the approaches implemented to achieve symptomatic and functional improvements, injection treatments have gained increasing attention due to the possibility of intra-articular delivery with reduced side effects compared to systemic therapies. In addition to well-established treatment options such as hyaluronic acid (HA), cortico-steroids (CS) and oxygen-ozone therapy, many other promising products have been employed in the last decades such as polydeoxyribonucleotide (PDRN) and biologic agents such as platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs). Moreover, ultrasound-guided intra-meniscal injection and X-ray-guided subchondral injection techniques have been introduced into clinical practice. Even when not supported by high evidence consensus, intra-articular CS and HA injections have gained precise indications for symptomatic relief and clinical improvement in OA. Biological products are strongly supported by in vitro evidence but there is still a lack of robust clinical evidence. PRP and MSCs seem to relieve OA symptoms through a regulation of the joint homeostasis, even if their capability to restore articular cartilage is still to be proved in vivo. Due to increasing interest in the subchondral bone pathology, subchondral injections have been developed with promising results in delaying joint replacement. Nevertheless, due to their recent development and the heterogeneity of the injected products (biologic agents or calcium phosphate), this approach still lacks strong enough evidence to be fully endorsed. Combined biological treatments, nano-molecular approaches, monoclonal antibodies and ‘personalized’ target therapies are currently under development or under investigation with the aim of expanding our armamentarium against knee OA. Cite this article: EFORT Open Rev 2021;6:501-509. DOI: 10.1302/2058-5241.6.210026

scholarly journals DDIS-31. A NOVEL BRAIN-PERMEANT CHEMOTHERAPEUTIC AGENT FOR THE TREATMENT OF BREAST CANCER LEPTOMENINGEAL METASTASIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi70-vi70
Author(s):  
Jiaojiao Deng ◽  
Sophia Chernikova ◽  
Wolf-Nicolas Fischer ◽  
Kerry Koller ◽  
Bernd Jandeleit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chemotherapeutic Agent ◽  
Treatment Options ◽  
Leptomeningeal Metastasis ◽  
Current Treatment ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Tnbc Cell Line

Abstract Leptomeningeal metastasis (LM), a spread of cancer to the cerebrospinal fluid and meninges, is universally and rapidly fatal due to poor detection and no effective treatment. Breast cancers account for a majority of LMs from solid tumors, with triple-negative breast cancers (TNBCs) having the highest propensity to metastasize to LM. The treatment of LM is challenged by poor drug penetration into CNS and high neurotoxicity. Therefore, there is an urgent need for new modalities and targeted therapies able to overcome the limitations of current treatment options. Quadriga has discovered a novel, brain-permeant chemotherapeutic agent that is currently in development as a potential treatment for glioblastoma (GBM). Recently, we have demonstrated dose-dependent in vitro and in vivo anti-tumor activity with various breast cancer cell lines including the human TNBC cell line MDA-MB-231. To evaluate the in vivo antitumor activity of the compound on LM, we used the mouse model of LM based on the internal carotid injection of luciferase-expressing MDA-MB-231-BR3 cells. Once the bioluminescence signal intensity from the metastatic spread reached (0.2 - 0.5) x 106photons/sec, mice were dosed i.v. (8 mg/kg once a week for nine weeks) or i.p. (4 or 8 mg/kg twice a week for nine weeks). Tumor growth was monitored by bioluminescence. The compound was well tolerated and caused a significant delay in metastatic growth resulting in significant extension of survival. Tumors regressed completely in ~ 28 % of treated animals in the i.p. group. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, Quadriga’s new agent could be effective as a therapeutic for both primary and metastatic brain tumors such as LM. REF: https://onlinelibrary.wiley.com/doi/full/10.1002/pro6.43

scholarly journals Metallo-β-Lactamases: Structure, Function, Epidemiology, Treatment Options, and the Development Pipeline

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Sara E. Boyd ◽  
David M. Livermore ◽  
David C. Hooper ◽  
William W. Hope
Keyword(s):  
Treatment Options ◽  
Carbapenem Resistance ◽  
Modern Medicine ◽  
Current Treatment ◽  
Structure And Function ◽  
Gram Negative Bacteria ◽  
Development Pipeline ◽  
And Function

ABSTRACT Modern medicine is threatened by the global rise of antibiotic resistance, especially among Gram-negative bacteria. Metallo-β-lactamase (MBL) enzymes are a particular concern and are increasingly disseminated worldwide, though particularly in Asia. Many MBL producers have multiple further drug resistances, leaving few obvious treatment options. Nonetheless, and more encouragingly, MBLs may be less effective agents of carbapenem resistance in vivo, under zinc limitation, than in vitro. Owing to their unique structure and function and their diversity, MBLs pose a particular challenge for drug development. They evade all recently licensed β-lactam–β-lactamase inhibitor combinations, although several stable agents and inhibitor combinations are at various stages in the development pipeline. These potential therapies, along with the epidemiology of producers and current treatment options, are the focus of this review.

scholarly journals Tissue-Specific Decellularized Extracellular Matrix Bioinks for Musculoskeletal Tissue Regeneration and Modeling Using 3D Bioprinting Technology

2021 ◽  
Vol 22 (15) ◽  
pp. 7837
Author(s):  
Wonbin Park ◽  
Ge Gao ◽  
Dong-Woo Cho
Keyword(s):  
Extracellular Matrix ◽  
Donor Site ◽  
Leading Edge ◽  
Donor Site Morbidity ◽  
3D Bioprinting ◽  
Musculoskeletal Tissue ◽  
Decellularized Extracellular Matrix ◽  
Homeostatic Function

The musculoskeletal system is a vital body system that protects internal organs, supports locomotion, and maintains homeostatic function. Unfortunately, musculoskeletal disorders are the leading cause of disability worldwide. Although implant surgeries using autografts, allografts, and xenografts have been conducted, several adverse effects, including donor site morbidity and immunoreaction, exist. To overcome these limitations, various biomedical engineering approaches have been proposed based on an understanding of the complexity of human musculoskeletal tissue. In this review, the leading edge of musculoskeletal tissue engineering using 3D bioprinting technology and musculoskeletal tissue-derived decellularized extracellular matrix bioink is described. In particular, studies on in vivo regeneration and in vitro modeling of musculoskeletal tissue have been focused on. Lastly, the current breakthroughs, limitations, and future perspectives are described.

scholarly journals Advances in Research of Adult Gliomas

2021 ◽  
Vol 22 (2) ◽  
pp. 924
Author(s):  
Alina Finch ◽  
Georgios Solomou ◽  
Victoria Wykes ◽  
Ute Pohl ◽  
Chiara Bardella ◽  
...  
Keyword(s):  
Brain Tumours ◽  
Treatment Options ◽  
Current Treatment ◽  
In Vivo Models ◽  
Malignant Brain Tumours ◽  
Current Therapies ◽  
Diffuse Gliomas ◽  
In Silico Models

Diffuse gliomas are the most frequent brain tumours, representing 75% of all primary malignant brain tumours in adults. Because of their locally aggressive behaviour and the fact that they cannot be cured by current therapies, they represent one of the most devastating cancers. The present review summarises recent advances in our understanding of glioma development and progression by use of various in vitro and in vivo models, as well as more complex techniques including cultures of 3D organoids and organotypic slices. We discuss the progress that has been made in understanding glioma heterogeneity, alteration in gene expression and DNA methylation, as well as advances in various in silico models. Lastly current treatment options and future clinical trials, which aim to improve early diagnosis and disease monitoring, are also discussed.

scholarly journals Pre-Innervated Tissue Engineered Muscle Promotes a Pro-Regenerative Microenvironment Following Volumetric Muscle Loss

2019 ◽  
Author(s):  
Suradip Das ◽  
Kevin D. Browne ◽  
Franco A. Laimo ◽  
Joseph C. Maggiore ◽  
Halimulati Kaisaier ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Functional Recovery ◽  
The Body ◽  
Muscle Loss ◽  
Skeletal Myocytes ◽  
Volumetric Muscle Loss ◽  
Nanofibrous Scaffolds ◽  
Multiple Challenges

AbstractVolumetric Muscle Loss (VML) is defined as traumatic or surgical loss of skeletal muscle tissue beyond the inherent regenerative capacity of the body, generally leading to a severe functional deficit. Autologous muscle grafts remain the prevalent method of treatment whereas recent muscle repair techniques using biomaterials and tissue engineering are still at a nascent stage and have multiple challenges to address to ensure functional recovery of the injured muscle. Indeed, appropriate somato-motor innervations remain one of the biggest challenges for both autologous muscle grafts as well as tissue engineered muscle constructs. We aim to address this challenge by developing Pre-Innervated Tissue Engineered Muscle comprised of long aligned networks of spinal motor neurons and skeletal myocytes. Here, we developed methodology to biofabricate long fibrils of pre-innervated tissue engineered muscle using a co-culture of myocytes and motor neurons on aligned nanofibrous scaffolds. Motor neurons lead to enhanced differentiation and maturation of skeletal myocytes in vitro. These pre-innervated tissue engineered muscle constructs when implanted in vivo in a rat VML model significantly increase satellite cell migration, micro-vessel formation, and neuromuscular junction density in the host muscle near the injury area at an acute time point as compared to non-pre-innervated myocyte constructs and nanofiber scaffolds alone. These pro-regenerative effects can potentially lead to enhanced functional neuromuscular regeneration following VML, thereby improving the levels of functional recovery following these devastating injuries.

Clinical Use of Bioactive Glasses for Maxillo-Facial Repair

2008 ◽  
Vol 377 ◽  
pp. 73-84 ◽  
Author(s):  
Ian Thompson ◽  
Larry L. Hench
Keyword(s):  
Bioactive Glass ◽  
Structural Characteristics ◽  
Donor Site ◽  
Donor Site Morbidity ◽  
Autogenous Bone ◽  
In Vitro Tests ◽  
Cell Cycles ◽  
Facial Surgery

Autogenous bone grafts are considered to be the gold standard in maxillo-facial surgery. However, drawbacks of donor site morbidity and unpredictable rates of resorbtion often limit their use. In vivo tests have shown that 45S5 bioactive glass particles placed in critical size bone defects lead to regeneration of new bone that has the structural characteristics and architecture of mature trabecular bone. In vitro tests using primary osteoblast cultures have shown that the bioactive glass particles release ionic dissolution products that provide genetic stimuli that control osteoblast cell cycles and lead to rapid growth of mineralized bone nodules. These in vitro and in vivo results led to approval of use of bioactive glass particles and monolithic bioactive glass implants for use in maxillo-facial reconstructions after removal of bone cysts and trauma, as described by several case histories.

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