Current Issue : April - June Volume : 2015 Issue Number : 2 Articles : 5 Articles
Introduction: Autologous fat grafting is commonly used to correct soft-tissue contour deformities. However, results\nare impaired by a variable and unpredictable resorption rate. Autologous adipose-derived stromal cells in combination\nwith lipoinjection (cell-assisted lipotransfer) seem to favor a long-term persistence of fat grafts, thus fostering the\ndevelopment of devices to be used in the operating room at the point of care, to isolate the stromal vascular fraction\n(SVF) and produce SVF-enhanced fat grafts with safe and standardized protocols. Focusing on patients undergoing\nbreast reconstruction by lipostructure, we analyzed a standard technique, a modification of the Coleman�s procedure,\nand three different commercially available devices (Lipokit, Cytori, Fastem), in terms of 1) ability to enrich fat grafts in\nstem cells and 2) clinical outcome at 6 and 12 months.\nMethods: To evaluate the ability to enrich stem cells, we compared, for each patient (n = 20), the standard lipoaspirate\nwith the respective stem cell-enriched one, analyzing yield, immunophenotype and colony-forming capacity of the SVF\ncells as well as immunophenotype, clonogenicity and multipotency of the obtained adipose stem cells (ASCs). Regarding\nthe clinical outcome, we compared, by ultrasonography imaging, changes at 6 and 12 months in the subcutaneous\nthickness of patients treated with stem-cell enriched (n = 14) and standard lipoaspirates (n = 16).\nResults: Both methods relying on the enzymatic isolation of primitive cells led to significant increase in the frequency, in\nthe fat grafts, of SVF cells as well as of clonogenic and multipotent ASCs, while the enrichment was less prominent\nfor the device based on the mechanical isolation of the SVF. From a clinical point of view, patients treated with\nSVF-enhanced fat grafts demonstrated, at six months, a significant superior gain of thickness of both the central and\nsuperior-medial quadrants with respect to patients treated with standard lipotransfer. In the median-median quadrant the\neffect was still persistent at 12 months, confirming an advantage of lipotransfer technique in enriching improving\nlong-term fat grafts.\nConclusions: This comparative study, based on reproducible biological and clinical parameters and endpoints, showed\nan advantage of lipotransfer technique in enriching fat grafts in stem cells and in favoring, clinically, long-term fat grafts....
Introduction: Ocular trauma is defined as a trauma caused by blunt or penetrating mechanisms on the eyeball\nand its peripheral structures, causing damage with different degrees of affection with temporary or permanent\nvisual function compromise. Ocular trauma is a major cause of preventable blindness worldwide; it constitutes 7%\nof all corporal injury and 10% to 15% of all eye diseases. Regenerative medicine research has opened up the\npossibility to use stem cells as a source of cell replacement, so that experimental studies on embryonic stem cells\nand bone marrow stem cells have been carried out. In this study, we analyzed the histopathological and\nspectroscopic changes in ocular tissue with trauma, treated with mouse pluripotent stem cells.\nMethods: Firstly, mouse embryonic stem cells were seeded. Subsequently, the obtained cells were implanted in a\nmurine model of scleral and retinal damage at the first, second, and fourth weeks post-trauma. At week 12 post-trauma,\nthe eyes were enucleated for histopathologic study (inflammatory response and histological integrity) and spectroscopic\nanalysis by Fourier transform infrared spectroscopy in the attenuated total reflection configuration. Data were analyzed\nby one-way analysis of variance.\nResults: Histopathological results showed that the experimental groups treated with stem cells presented a decrease in\nthe inflammatory response, and the histological integrity was restored, which contrasted with the experimental group\ntreated with saline solution. Moreover, in the spectroscopic analysis, characteristic bands of biological samples were\nobserved in all tissues, highlighting in healthy tissues the presence of C = O bond at 1,745 cm-1, which was not\nobserved in the injured and treated tissues. Also, the absorption spectrum of the tissues treated with embryonic stem\ncells showed bands whose intensity was high at around 1,080 to 1,070 cm-1. It has been reported that these bands are\ncharacteristic of pluripotent stem cells.\nConclusions: The implant of embryonic stem cells could be a useful therapeutic treatment after traumatic eye injuries\nor many other eye diseases to reduce the inflammatory response and restore histological integrity. Furthermore, the\nspectroscopic technique could be used as a complementary technique for detecting stem cell incorporation into\nvarious tissues...
Introduction: The use of hematopoietic cell transplantation (HCT) has previously been shown to ameliorate cutaneous\nblistering in pediatric patients with recessive dystrophic epidermolysis bullosa (RDEB), an inherited skin disorder that\nresults from loss-of-function mutations in COL7A1 and manifests as deficient or absent type VII collagen protein (C7)\nwithin the epidermal basement membrane. Mesenchymal stem cells (MSCs) found within the HCT graft are believed to\nbe partially responsible for this amelioration, in part due to their intrinsic immunomodulatory and trophic properties\nand also because they have been shown to restore C7 protein following intradermal injections in models of RDEB.\nHowever, MSCs have not yet been demonstrated to improve disease severity as a stand-alone systemic infusion\ntherapy. Improving the efficacy and functional utility of MSCs via a pre-transplant conditioning regimen may bring\nsystemic MSC infusions closer to clinical practice.\nMethods: MSCs were isolated from 2- to 4-week-old mice and treated with varying concentrations of transforming\ngrowth factor-? (TGF?; 5-20 ng/mL), tumor necrosis factor- ? (TNF?; 10-40 ng/mL), and stromal cell-derived factor 1-?\n(SDF-1?; 30 ng/mL) for 24-72 hours.\nResults: We demonstrate that treating murine MSCs with exogenous TGF? (15 ng/mL) and TNF? (30 ng/mL) for 48 hours\ninduces an 8-fold increase in Col7a1 expression and a significant increase in secretion of C7 protein, and that the effects\nof these cytokines are both time and concentration dependent. This cytokine treatment also promotes a 4-fold increase\nin Tsg-6 expression, a gene whose product is associated with improved wound-healing and immunosuppressive features.\nFinally, the addition of exogenous SDF-1? to this regimen induces a simultaneous upregulation of Col7a1, Tsg-6, and Cxcr4\nexpression.\nConclusions: These data suggest that preconditioning represents a feasible method for improving the functional utility\nof MSCs in the context of RDEB stem cell transplantation, and also highlight the applicability of preconditioning principles\ntoward other cell-based therapies aimed at treating RDEB patients....
Introduction: The administration of stem cells holds promise as a potential therapy for spinal cord injury (SCI).\nMesenchymal stem cells have advantages for clinical applications, since they can be easily obtained, are suitable for\nautologous transplantation and have been previously shown to induce regeneration of the spinal cord in\nexperimental settings. Here we evaluated the feasibility, safety and potential efficacy of autologous transplantation\nof mesenchymal stem cells in subjects with chronic complete SCI.\nMethod: We conducted a phase I, non-controlled study in 14 subjects of both genders aging between 18 to 65 years,\nwith chronic traumatic SCI (>6 months), at thoracic or lumbar levels, classified as American Spinal Injury Association\n(ASIA) A - complete injury. Baseline somatosensory evoked potentials (SSEP), spinal magnetic resonance imaging\n(MRI) and urodynamics were assessed before and after treatment. Pain rating was performed using the McGill\nPain Questionnaire and a visual analogue score scale. Bone marrow-derived mesenchymal stem cells were cultured\nand characterized by flow cytometry, cell differentiation assays and G-band karyotyping. Mesenchymal stem cells were\ninjected directly into the lesion following laminectomy and durotomy.\nResults: Cell transplantation was an overall safe and well-tolerated procedure. All subjects displayed variable improvements\nin tactile sensitivity and eight subjects developed lower limbs motor functional gains, principally in the hip flexors. Seven\nsubjects presented sacral sparing and improved American Spinal Injury Association impairment scale (AIS) grades to B\nor C ââ?¬â?? incomplete injury. Nine subjects had improvements in urologic function. One subject presented changes\nin SSEP 3 and 6 months after mesenchymal stem cells transplantation. Statistically significant correlations between\nthe improvements in neurological function and both injury size and level were found.\nConclusion: Intralesional transplantation of autologous mesenchymal stem cells in subjects with chronic, complete\nspinal cord injury is safe, feasible, and may promote neurological improvements....
Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrotic lung disease, resulting in\nrespiratory insufficiency and reduced survival. Pulmonary fibrosis is a result of repeated alveolar epithelial\nmicroinjuries, followed by abnormal regeneration and repair processes in the lung. Recently, stem cells and their\nsecretome have been investigated as a novel therapeutic approach in pulmonary fibrosis. We evaluated the\npotential of induced pluripotent stem cells (iPSC) conditioned media (iPSC-cm) to regenerate and repair the\nalveolar epithelium in vitro and improve bleomycin induced lung injury in vivo.\nMethods: IPSC-cm was collected from cultured iPSC derived from human foreskin fibroblasts and its biological\neffects on alveolar epithelial wound repair was studied in an alveolar wound healing assay in vitro. Furthermore,\niPSC-cm was intratracheally instilled 7 days after bleomycin induced injury in the rat lungs and histologically and\nbiochemically assessed 7 days after instillation.\nResults: iPSC-cm increased alveolar epithelial wound repair in vitro compared with medium control. Intratracheal\ninstillation of iPSC-cm in bleomycin-injured lungs reduced the collagen content and improved lung fibrosis in the\nrat lung in vivo. Profibrotic TGFbeta1 and ?-smooth muscle actin (?-sma) expression were markedly reduced in the\niPSC-cm treated group compared with control. Antifibrotic hepatocyte growth factor (HGF) was detected in\niPSC-cm in biologically relevant levels, and specific inhibition of HGF in iPSC-cm attenuated the antifibrotic effect of\niPSC-cm, indicating a central role of HGF in iPSC-cm.\nConclusion: iPSC-cm increased alveolar epithelial wound repair in vitro and attenuated bleomycin induced fibrosis\nin vivo, partially due to the presence of HGF and may represent a promising novel, cell free therapeutic option\nagainst lung injury and fibrosis....
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