|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Development of cellular therapy for the treatment of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2011 Apr 20; Authors: Wang HJ, Chuang YC, Chancellor MB Stress urinary incontinence (SUI) is highly prevalent and associated with a reduced quality of life. An intact rhabdosphincter at the mid-urethra is mandatory to maintain urinary continence. Adult stem cell injection therapy for the regenerative repair of an impaired sphincter is currently at the forefront of incontinence research. The implanted cells will fuse with muscle and release trophic factors promoting nerve and muscle integration. Hereby, we review the use of mesenchymal stem cell therapy for SUI and the experience with the development of muscle-derived stem cells. PMID: 21505907 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | In vitro targeted magnetic delivery and tracking of superparamagnetic iron oxide particles labeled stem cells for articular cartilage defect repair. J Huazhong Univ Sci Technolog Med Sci. 2011 Apr;31(2):204-209 Authors: Feng Y, Jin X, Dai G, Liu J, Chen J, Yang L To assess a novel cell manipulation technique of tissue engineering with respect to its ability to augment superparamagnetic iron oxide particles (SPIO) labeled mesenchymal stem cells (MSCs) density at a localized cartilage defect site in an in vitro phantom by applying magnetic force. Meanwhile, non-invasive imaging techniques were use to track SPIO-labeled MSCs by magnetic resonance imaging (MRI). Human bone marrow MSCs were cultured and labeled with SPIO. Fresh degenerated human osteochondral fragments were obtained during total knee arthroplasty and a cartilage defect was created at the center. Then, the osteochondral fragments were attached to the sidewalls of culture flasks filled with phosphate-buffered saline (PBS) to mimic the human joint cavity. The SPIO-labeled MSCs were injected into the culture flasks in the presence of a 0.57 Tesla (T) magnetic force. Before and 90 min after cell targeting, the specimens underwent T2-weighted turbo spin-echo (SET2WI) sequence of 3.0 T MRI. MRI results were compared with histological findings. Macroscopic observation showed that SPIO-labeled MSCs were steered to the target region of cartilage defect. MRI revealed significant changes in signal intensity (P<0.01). HE staining exibited that a great number of MSCs formed a three-dimensional (3D) cell "sheet" structure at the chondral defect site. It was concluded that 0.57 T magnetic force permits spatial delivery of magnetically labeled MSCs to the target region in vitro. High-field MRI can serve as an very sensitive non-invasive technique for the visualization of SPIO-labeled MSCs. PMID: 21505986 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Elastomeric PGS Scaffolds in Arterial Tissue Engineering. J Vis Exp. 2011;(50) Authors: Lee KW, Wang Y Cardiovascular disease is one of the leading cause of mortality in the US and especially, coronary artery disease increases with an aging population and increasing obesity(1). Currently, bypass surgery using autologous vessels, allografts, and synthetic grafts are known as a commonly used for arterial substitutes(2). However, these grafts have limited applications when an inner diameter of arteries is less than 6 mm due to low availability, thrombotic complications, compliance mismatch, and late intimal hyperplasia(3,4). To overcome these limitations, tissue engineering has been successfully applied as a promising alternative to develop small-diameter arterial constructs that are nonthrombogenic, robust, and compliant. Several previous studies have developed small-diameter arterial constructs with tri-lamellar structure, excellent mechanical properties and burst pressure comparable to native arteries(5,6). While high tensile strength and burst pressure by increasing collagen production from a rigid material or cell sheet scaffold, these constructs still had low elastin production and compliance, which is a major problem to cause graft failure after implantation. Considering these issues, we hypothesized that an elastometric biomaterial combined with mechanical conditioning would provide elasticity and conduct mechanical signals more efficiently to vascular cells, which increase extracellular matrix production and support cellular orientation. The objective of this report is to introduce a fabrication technique of porous tubular scaffolds and a dynamic mechanical conditioning for applying them to arterial tissue engineering. We used a biodegradable elastomer, poly (glycerol sebacate) (PGS)(7) for fabricating porous tubular scaffolds from the salt fusion method. Adult primary baboon smooth muscle cells (SMCs) were seeded on the lumen of scaffolds, which cultured in our designed pulsatile flow bioreactor for 3 weeks. PGS scaffolds had consistent thickness and randomly distributed macro- and micro-pores. Mechanical conditioning from pulsatile flow bioreactor supported SMC orientation and enhanced ECM production in scaffolds. These results suggest that elastomeric scaffolds and mechanical conditioning of bioreactor culture may be a promising method for arterial tissue engineering. PMID: 21505410 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Neurogenesis of adipose-derived stem cells in hydrogel. J Huazhong Univ Sci Technolog Med Sci. 2011 Apr;31(2):174-177 Authors: Xie X, Tang Z, Chen J, Yang J, Zeng W, Liu N, Liu Y Adipose tissue is a readily available source of adult stem cells with multipotent properties suitable for tissue engineering and regenerative medical applications. Peptide hydrogel is a novel biomaterial which provides three-dimensional microenvironments for a variety of cells for tissue grafting. In this study, adipose-derived stem cells (ADSCs) were isolated from rats, seeded into the peptide hydrogel polymer scaffolds and cultured in Neurobasal (NB) media supplemented with B27, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Ten days after the culture, some cells were expanded into clonal populations in which the expression of both Nestin and Brdu was detected but only Brdu expression was detected in the cells that were not expanded into clonal populations. Our results suggested that ADSCs in peptide hydrogel polymer scaffolds can be induced to differentiate into cells capable of expressing the neuron-associated markers, self-renewal and self-propagation. PMID: 21505979 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Differentiation of mesenchymal stem cells towards a nucleus pulposus-like phenotype utilizing simulated microgravity In vitro. J Huazhong Univ Sci Technolog Med Sci. 2011 Apr;31(2):199-203 Authors: Luo W, Xiong W, Qiu M, Lv Y, Li Y, Li F Mesenchymal stem cells (MSCs) were induced into a nucleus pulposus-like phenotype utilizing simulated microgravity in vitro in order to establish a new cell-based tissue engineering treatment for intervertebral disc degeneration. For induction of a nucleus pulposus-like phenotype, MSCs were cultured in simulated microgravity in a chemically defined medium supplemented with 0 (experimental group) and 10 ng/mL (positive control group) of transforming growth factor β1 (TGF-β1). MSCs cultured under conventional condition without TGF-β1 served as blank control group. On the day 3 of culture, cellular proliferation was determined by WST-8 assay. Differentiation markers were evaluated by histology and reverse transcriptase-polymerase chain reaction (RT-PCR). TGF-β1 slightly promoted the proliferation of MSCs. The collagen and proteoglycans were detected in both groups after culture for 7 days. The accumulation of proteoglycans was markedly increased. The RT-PCR revealed that the gene expression of Sox-9, aggrecan and type II collagen, which were chondrocyte specific, was increased in MSCs cultured under simulated microgravity for 3 days. The ratio of proteoglycans/collagen in blank control group was 3.4-fold higher than positive control group, which denoted a nucleus pulposus-like phenotype differentiation. Independent, spontaneous differentiation of MSCs towards a nucleus pulposus-like phenotype in simulated microgravity occurred without addition of any external bioactive stimulators, namely factors from TGF-β family, which were previously considered necessary. PMID: 21505985 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Isolation and characterization of mesenchymal stem cells from the fat layer on the density gradient separated bone marrow. Stem Cells Dev. 2011 Apr 19; Authors: Insausti CL, Blanquer M, Meseguer L, López-Martínez MC, Ferez X, Rodriguez FJ, Cabañas V, Funes C, Nicolás FJ, Majado MJ, Moraleda JM The density gradient centrifugation method was originally designed for the isolation of mononuclear peripheral blood cells and rapidly adapted to fractionate bone marrow (BM) cells. This method involves the use of gradient density solutions with low viscosity and low osmotic pressure that allows erythrocytes and more mature cells gravitate to the bottom at a density fraction superior to 1.080 g/dl; mononuclear cells (MNCs) held in the plasma-solution inter-phase at a density between 1.053 and 1.073 g/dl; plasma, dilution medium and anticoagulant occupy a density less than 1.050 g/dl and the fat cells float due their very low density. Bone marrow (BM) MSCs are usually obtained after the separation and cultures of BM- mononuclear cells (MNCs) from the plasma-solution inter-phase, which is traditionally considered the only source of progenitor cells (hematopoietic and non-hematopoietic). In the present study we presented evidences that MSCs could be isolated from the very low-density cells of the fat layer. In addition we demonstrated that the MSCs obtained from these cells have similar immunophenotypic characteristics, and similar proliferative and differentiation potential to those obtained from the MNCs at plasma-solution inter-phase. The method represents a simple and cost effective way to increase the MSCs yield from each BM donor, without the need to look for other sources, additional manipulation of cells, risks of contamination or disturbances of the potential of differentiation. These cells might serve as a complementary source of MSCs to facilitate preclinical and clinical application in tissue engineering and cell therapy. PMID: 21504358 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A smart bilayer scaffold of elastin-like recombinamer and collagen for soft tissue engineering. J Mater Sci Mater Med. 2011 Apr 20; Authors: Kinikoglu B, Rodríguez-Cabello JC, Damour O, Hasirci V Elastin-like recombinamers (ELRs) are smart, protein-based polymers designed with desired peptide sequences using recombinant DNA technology. The aim of the present study was to produce improved tissue engineering scaffolds from collagen and an elastin-like protein tailored to contain the cell adhesion peptide RGD, and to investigate the structural and mechanical capacities of the resulting scaffolds (foams, fibers and foam-fiber bilayer scaffolds). The results of the scanning electron microscopy, mercury porosimetry and mechanical testing indicated that incorporation of ELR into the scaffolds improved the uniformity and continuity of the pore network, decreased the pore size (from 200 to 20 μm) and the fiber diameter (from 1.179 μm to 306 nm), broadened the pore size distribution (from 70-200 to 4-200 μm) and increased their flexibility (from 0.007 to 0.011 kPa(-1)). Culture of human fibroblasts and epithelial cells in ELR-collagen scaffolds showed the positive contribution of ELR on proliferation of both types of cells. PMID: 21505829 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative Medicine and Organ Transplantation: Past, Present, and Future. Transplantation. 2011 Apr 18; Authors: Orlando G, Wood KJ, Stratta RJ, Yoo JJ, Atala A, Soker S This overview traces the history of regenerative medicine pertinent to organ transplantation, illustrates potential clinical applications reported to date, and highlights progress achieved in the field of complex modular organ engineering. Regenerative medicine can now produce relatively simple tissues such as skin, bladders, vessels, urethras, and upper airways, whereas engineering or generation of complex modular organs remains a major challenge. Ex vivo organ engineering may benefit from complementary investigations in the fields of developmental biology and stem cells and transplantation before its full potential can be realized. PMID: 21505379 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Contamination of Mesenchymal Stem-Cells with Fibroblasts Accelerates Neurodegeneration in an Experimental Model of Parkinson's Disease. Stem Cell Rev. 2011 Apr 19; Authors: Pereira MC, Secco M, Suzuki DE, Janjoppi L, Rodini CO, Torres LB, Araújo BH, Cavalheiro EA, Zatz M, Okamoto OK Pre-clinical studies have supported the use of mesenchymal stem cells (MSC) to treat highly prevalent neurodegenerative diseases such as Parkinson's disease (PD) but preliminary trials have reported controversial results. In a rat model of PD induced by MPTP neurotoxin, we first observed a significant bilateral preservation of dopaminergic neurons in the substantia nigra and prevention of motor deficits typically observed in PD such as hypokinesia, catalepsy, and bradykinesia, following intracerebral administration of human umbilical cord-derived MSC (UC-MSC) early after MPTP injury. However, surprisingly, administration of fibroblasts, mesenchymal cells without stem cell properties, as a xenotransplantation control was highly detrimental, causing significant neurodegeneration and motor dysfunction independently of MPTP. This observation prompted us to further investigate the consequences of transplanting a MSC preparation contaminated with fibroblasts, a plausible circumstance in cell therapy since both cell types display similar immunophenotype and can be manipulated in vitro under the same conditions. Here we show for the first time, using the same experimental model and protocol, that transplantation of UC-MSC induced potent neuroprotection in the brain resulting in clinical benefit. However, co-transplantation of UC-MSC with fibroblasts reverted therapeutic efficacy and caused opposite damaging effects, significantly exacerbating neurodegeneration and motor deficits in MPTP-exposed rats. Besides providing a rationale for testing UC-MSC transplantation in early phases of PD aiming at delaying disease progression, our pre-clinical study suggests that fibroblasts may be common cell contaminants affecting purity of MSC preparations and clinical outcome in stem cell therapy protocols, which might also explain discrepant clinical results. PMID: 21503590 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Cardiac regenerative therapy: Which type of cell will breast the tape?/Autologous stem cell therapy with surgical myocardial revascularization-The Rostock University experience.] Anadolu Kardiyol Derg. 2011 Apr 18; Authors: Yiğiner O, Kardeşoğlu E, Uz O, Ozmen N, Cebeci BS PMID: 21501989 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Rosuvastatin Treatment Activates JAK-STAT Pathway and Increases Efficacy of Allogeneic Mesenchymal Stem Cell Transplantation in Infarcted Hearts. Circ J. 2011 Apr 19; Authors: Xu H, Yang YJ, Qian HY, Tang YD, Wang H, Zhang Q Background: Widespread death of implanted cells hampers the development of stem cell therapy for acute myocardial infarction (AMI). Our previous studies indicated that statins can protect implanted mesenchymal stem cells (MSCs) against the post-infarct microenvironment, thus increasing the therapeutic effect. However, the underlying mechanisms are unclear. The JAK-STAT pathway participates in regulation of stress responses of the myocardium to various insults. This study aimed to detect whether rosuvastatin (ROSU) facilitates the survival, engraftment, and differentiation of allogeneic bone marrow-derived MSCs in the post-infarct heart via the JAK-STAT signaling pathway. Methods and Results: Female Sprague-Dawley rats were randomized into 5 groups: AMI (control), ROSU gavage (group R), MSCs transplantation (group M), MSCs and ROSU (group M+R), or MSCs, ROSU and a JAK2 inhibitor AG-490 (group M+R+AG). MSCs from male rats were injected into the myocardium 1 week after AMI. Cardiac function and histology, as well as the expression of Y-chromosomal genes and JAK-STAT signaling proteins, were examined at 4 weeks after transplantation. Better functional recovery, increased survival and differentiation of MSCs occurred in group M+R. Furthermore, phosphorylation of JAK2 and STAT3 was higher in group M+R. The effects of ROSU, as well as of activated JAK-STAT proteins, could be attenuated by AG-490. Conclusions: ROSU treatment improves the efficacy of stem cell transplantation in infarcted hearts by activation of the JAK2-STAT3 signaling pathway. PMID: 21502705 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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