fellow, U of A
Adipose stem cells can be transformed into muscle cells to treat bladder underactive conditions.
Stem cells form a renewable source for cellular therapy to treatment different diseases of urogenital tract. Adipose stem cells can be extracted from our body fat and then injected back to our urogenital system to treat different diseases like impotence and urinary incontinence. Also, they can be injected into the urinary bladder to replenish the the defective muscle cells and prevent urinary retention.
Abstract: Adipose tissue-derived stem cells (ASCs) are known to be tissue-healing promoters due to their cellular plasticity and secretion of paracrine factors. Cultured ASC sheets provide a novel method of ASCs application and can retain ASCs at the targeted tissue. The purpose of this systematic review is to evaluate preclinical studies using adipose tissue-derived cell (ASC) sheet transplantation therapy for promoting tissue healing. Firstly, we searched databases to identify studies of ASC sheet therapy in different experimental animal models, and then determined the quality score of studies using SYRCLE's risk bias tool. A total of 18 included studies examined the role of ASC sheets on tissue healing and function in models for myocardial infarction, dilated cardiomyopathy, full-thickness skin wounds, hind limb ischemia, esophageal strictures and oral ulcers. ASC sheet application after myocardial infarction improved survival rate, cardiac function and capillary density and reduced the extent of fibrosis. Application of ASC sheets to a full thickness skin wound decreased the wound size and stimulated wound maturation. In the hind limb ischemia model, ASC sheet application improved limb perfusion, and capillary density and decreased the amount of ischemic tissue and inflammation. ASC sheet application to mucosal wounds of the gastrointestinal system accelerated wound healing and decreased the degree of stricture and fibrosis. Taken together, transplanted ASC sheets had a positive effect on tissue healing and reconstruction in these pre-clinical studies. The reported favorable effects of ASC sheet therapy in various tissue healing applications may be implemented in future translational studies. It is suggested that future preclinical animal model studies of ASC sheet therapy should concern standardization of culture techniques and investigate the mechanisms of action. In addition, clearly indicated experimental set-ups according to the SYRCLE's guidelines should improve study quality and validity.
Pub.: 01 Jul '17, Pinned: 28 Jul '17
Abstract: Peripheral nerve regeneration requires coordinated functions of supporting cells (e.g. Schwann cells) and neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF), but nerve regeneration is usually far from complete. Here we constructed a Cre/loxP-based hybrid baculovirus (BV) vector which enabled intracellular formation of episomal DNA minicircle for effective transduction of rat adipose-derived stem cells (ASCs) and prolonged expression of functional GDNF capable of recruiting Schwann cells. The GDNF expression persisted for >20 days with the peak level (≈128 ng/ml) tremendously exceeding the picogram levels of GDNF secreted by neuroprogenitor cells. We further developed a facile method to fabricate and transduce cell sheets composed of undifferentiated ASCs in 2 days, without the need of thermo-responsive polymer commonly used for cell sheet fabrication. Implantation of the hybrid BV-engineered, GDNF-expressing ASCs sheets into sciatic nerve transection site in rats significantly improved the nerve repair, as judged from the enhanced functional recovery, nerve reinnervation, electrophysiological functionality, Schwann cells proliferation/infiltration, axon regeneration, myelination and angiogenesis. The hybrid BV is able to functionalize ASCs sheets by intracellular episomal DNA minicircle formation that circumvents undesired gene integration, and the ASCs sheets fabrication is rapid and simple. These data and features implicate the potentials of ASCs sheets functionalized by the hybrid BV for peripheral nerve regeneration.
Pub.: 29 Jun '17, Pinned: 28 Jul '17
Abstract: Synthetic non-absorbable meshes are widely used to augment surgical repair of pelvic organ prolapse (POP) and stress urinary incontinence (SUI), but these meshes are associated with serious complications. This study compares the attachment and extracellular matrix (ECM) production of adipose-derived stem cells (ADSCs) on different biodegradable nanomaterials to develop tissue engineered repair materials.Rat ADSCs were isolated and cultured on electrospun poly-L-lactic acid (PLA) and electrospun poly(L-lactide)-trimethylene carbonate-gycolide (PLTG) terpolymers for 1 and 2 weeks. Samples were tested for cell proliferation (cell counting kit-8), microstructure, and morphology (scanning electron microscopy), production of ECM components (immunostaining for collagen I, collagen III, and elastin) and biomechanical properties (uniaxial tensile methods).The ADSCs showed good attachment and proliferation on both PLA and PLTG scaffolds. The production of collagen I and collagen III on both scaffolds was greater at 14 days than at 7 days and was greater on PLTG scaffolds than on PLA scaffolds, but these differences were not significant. The addition of ADSCs onto scaffolds led to a significant increase in the biomechanical properties of both PLA and PLTG scaffolds compared with unseeded scaffolds.These data support the use of both PLA and PLTG as tissue-engineered repair materials for POP or SUI.
Pub.: 22 Jul '17, Pinned: 28 Jul '17
Abstract: Urethral strictures remain a reconstructive challenge, due to less than satisfactory outcomes and high incidence of stricture recurrence. An "ideal" urethral reconstruction should establish similar architecture and function as the original urethral wall. We fabricated a novel tissue-engineered bionic urethras using cell sheet technology and report their viability in a canine model. Small amounts of oral and adipose tissues were harvested, and adipose-derived stem cells, oral mucosal epithelial cells, and oral mucosal fibroblasts were isolated and used to prepare cell sheets. The cell sheets were hierarchically tubularized to form 3-layer tissue-engineered urethras and labeled by ultrasmall super-paramagnetic iron oxide (USPIO). The constructed tissue-engineered urethras were transplanted subcutaneously for 3 weeks to promote the revascularization and biomechanical strength of the implant. Then, 2 cm length of the tubularized penile urethra was replaced by tissue-engineered bionic urethra. At 3 months of urethral replacement, USPIO-labeled tissue-engineered bionic urethra can be effectively detected by MRI at the transplant site. Histologically, the retrieved bionic urethras still displayed 3 layers, including an epithelial layer, a fibrous layer, and a myoblast layer. Three weeks after subcutaneous transplantation, immunofluorescence analysis showed the density of blood vessels in bionic urethra was significantly increased following the initial establishment of the constructs and was further up-regulated at 3 months after urethral replacement and was close to normal level in urethral tissue. Our study is the first to experimentally demonstrate 3-layer tissue-engineered urethras can be established using cell sheet technology and can promote the regeneration of structural and functional urethras similar to normal urethra.
Pub.: 27 Jul '17, Pinned: 28 Jul '17
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