Application of Tissue Engineering to Pelvic Organ Prolapse and Stress Urinary Incontinence

Synthetic or biological materials can be used for the surgical repair of pelvic organ prolapse (POP) or stress urinary incontinence (SUI). While non‐degradable synthetic mesh has a low failure rate, it is prone to complications such as infection and erosion, particularly in the urological/gynecological setting when subject to chronic influences of gravity and intermittent, repetitive strain. Biological materials have lower complication rates, although allografts and xenografts have a high risk of failure and the theoretical risk of infection. Autografts are used successfully for the treatment of SUI and are not associated with erosion; however, can lead to morbidity at the donor site. Tissue engineering has thus become the focus of interest in recent years as researchers seek an ideal tissue remodeling material for urogynecological repair. Herein, we review the directions of current and future research in this exciting field. Electrospun poly‐L‐lactic acid (PLA) and porcine small intestine submucosa (SIS) are two promising scaffold material candidates. Adipose‐derived stem cells (ADSCs) appear to be a suitable cell type for scaffold seeding, and cells grown on scaffolds when subjected to repetitive biaxial strain show more appropriate biomechanical properties for clinical implantation. After implantation, an appropriate level of acute inflammation is important to precipitate moderate fibrosis and encourage tissue strength. New research directions include the use of bi...
Source: LUTS: Lower Urinary Tract Symptoms - Category: Urology & Nephrology Authors: Tags: REVIEW ARTICLE Source Type: research

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Satellite cells are residential muscle stem cells that express a paired box transcription factor PAX7. Pax7 has been shown to be involved in determination of myogenic cell lineage during development, yet it is also required for the postnatal muscle growth, muscle regeneration and maintenance of the satellite cell pool. Although the functions of Pax7 have been studied thoroughly, its interacting partners in myogenic cells in vivo are largely unknown due to the lack of proper antibodies for immunoprecipitation.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Urine-derived stem cells (USCs) are known to be a very promising source of stem cells, in addition their isolation is non-invasive, relatively quick and simple, affordable, ubiquitous, and readily accepted by patients. The USCs transcriptional profiling showed a great variability across individuals probably due to the co-presence of distinct cell types. The lack of specific and unique cell surface markers for the identification of cell types makes the separation difficult. In order to separate the USCs sub-populations, we used the new technology Celector that sorts the cells based only on their physical characteristics.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Anoctamin 5 (ANO5) belongs to the Anoctamin family of transmembrane proteins and has been suggested to play a part in muscle cell membrane fusion and repair. Mutations in the ANO5 gene are a common cause of muscular dystrophy. Little is known about the pathophysiology in ANO5 ‐related muscular dystrophy. The purpose of this study was to investigate whether inflammatory changes are present in patients with ANO5 myopathy by making a systematic histological and MRI-based evaluation of muscles. Muscle biopsies from 24 patients diagnosed with ANO5 myopathy were reviewed.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by the absence of dystrophin protein. Upon exhaustion of the regenerative capacity of muscle, there is an imbalance between muscle damage and repair. Insulin-like growth factor 1 (IGF-1) plays an essential role in increasing muscle mass and strength, reducing degeneration, inhibiting chronic inflammation and increasing the proliferation potential of satellite cells. Although liver is the main source of IGF-1, it is also expressed in different tissues including skeletal muscle.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
X-linked dilated cardiomyopathy (XLDCM) is a serious condition caused by abnormalities in the DMD gene (dystrophin gene). The affected patients did not have major skeletal weakness but presented with early signs of heart failure, and deteriorated quickly despite medical treatment resulting in early death. Currently there is no curative treatment and heart transplantation is often required. We study the pathomechanism of the DMD-associated XLDCM with mutation in the first exon-intron boundary, through examination of dystrophin isoforms expression and the functional characterization of the manifested cardiomyocytes generated...
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Dysferlinopathies are a group of muscular dystrophies caused by recessive mutations in the DYSF gene encoding the dysferlin protein. These muscular dystrophies, which affect at least 5,000 people in the world, are characterised by skeletal muscle degeneration and weakness. Dysferlin is a transmembrane protein located in the muscle fibers sarcolemma. This protein is involved in several muscle cell functions like T tubule formation, vesicle trafficking and membrane repair. In 2009, a study showed the presence of fourteen dysferlin transcripts from alternative splicing (Pramono Z.A.D.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Idiopathic inflammatory myopathies (IIM) involve chronic inflammation of skeletal muscle and subsequent muscle degeneration due to an uncontrolled autoimmune response. The mechanisms leading to pathogenesis are not well understood, however IIM may be triggered by increased exposure of intramuscular antigens due to the defective sarcolemmal membrane repair. Sarcolemmal membrane repair involves an active resealing mechanism that restores barrier function of the membrane after injury and is a critical component of maintaining normal cellular physiology.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Efficient cell migration requires cellular polarization, which is characterized by the formation of leading and trailing edges, appropriate positioning of the nucleus and reorientation of the Golgi apparatus and centrosomes towards the leading edge. Migration also requires the development of an asymmetrical front-to-rear calcium gradient to regulate focal adhesion assembly and actomyosin contractility. Here we demonstrate that silencing of syndecan-4, a transmembrane heparan sulfate proteoglycan, interferes with the correct polarization of migrating mammalian myoblasts (i.e., activated satellite stem cells).
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene. Although DMD is a progressive degenerative disease, there is evidence for early, embryonic-stage defects in myogenesis and gene expression in DMD. By understanding how these defects initiate and contribute to DMD pathology, we may be better positioned to identify and utilize DMD therapies. Using single-cell RNAseq, we have identified one of the earliest known DMD phenotypes: a novel transcriptional trajectory of DMD human induced pluripotent stem cells (hiPSCs) undergoing myogenesis.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Gene editing in cells has revolutionized the paradigm of modern cell biology. The ease of use of the CRISPR/Cas9 system for gene manipulation has led to rapid and wide adoption across many fields, including biological research, biotechnology and medicine. This technology allows gene modification by producing a specific double stranded cut in the DNA and the repair by homology-independent targeted insertion (HITI) of DNA. We used CRISPR/CAS9 to modify specific mutations in-vitro in a muscular disorder to show its potential use as a therapeutic tool.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
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