|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | The California Stem Cell Report has been named one of the 25 best stem cell blogs by a web site targeting readers interested in nursing education.
In preparing the list, nursingschools.net said,
"Whether you're pursuing a career in medicine or science, if you'd like to keep up with these advances, then blogs on the issue are one of the best tools out there. Here, you'll find a collection of | | | | | | | | | | | | | | | | | | | | | | | | | Simultaneous regeneration of articular cartilage and subchondral bone in vivo using MSCs induced by a spatially controlled gene delivery system in bilayered integrated scaffolds. Biomaterials. 2011 Apr 11; Authors: Chen J, Chen H, Li P, Diao H, Zhu S, Dong L, Wang R, Guo T, Zhao J, Zhang J Engineering complex tissues is important but difficult to achieve in tissue regeneration. Osteochondral tissue engineering for the repair of osteochondral defect, involving simultaneous regeneration of bone and cartilage, has attracted considerable attention and also serves as an optimal model system for developing effective strategies aimed at regenerating complex tissues. In the present study, we formulated a bilayered gene-activated osteochondral scaffold consisting of plasmid TGF-β1-activated chitosan-gelatin scaffold for chondrogenic layer and plasmid BMP-2-activated hydroxyapatite/chitosan-gelatin scaffold for osteogenic layer. Mesenchymal stem cells seeded in each layer of the bilayered gene- activated osteochondral scaffold showed significant cell proliferation, high expression of TGF-β1 protein and BMP-2 protein respectively. The results showed that spatially controlled and localized gene delivery system in the bilayered integrated scaffolds could induce the mesenchymal stem cells in different layers to differentiate into chondrocytes and osteoblasts in vitro, respectively, and simultaneously support the articular cartilage and subchondral bone regeneration in the rabbit knee ostochondral defect model. This study gives the evidence that multi-tissue regeneration through the combination of biomimetic and multi-phasic scaffold design, spatially controlled and localized gene delivery system and multi-lineage differentiation of a single stem cell population represents a promising strategy for facilitating the development of complex tissue or organ systems. PMID: 21489619 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The Challenge of Integrating Devices into the Central Nervous System. Crit Rev Biomed Eng. 2011;39(1):29-44 Authors: Tresco PA, Winslow BD Implanted biomedical devices are playing an increasingly important role in the treatment of central nervous system disorders. While devices such as deep brain stimulation electrodes and drug delivery systems have shown clinical success in chronic applications, other devices such as nerve guidance substrates and recording electrodes that operate over a very short length scale have not had the same kind of clinical impact. By reviewing what is currently known about the brain tissue response to implanted electrodes, the authors propose that the foreign-body response, which changes the tissue structure immediately surrounding implanted devices, may be the reason near-function devices are stalled in preclinical development. The article concludes by reviewing recent efforts to reduce the foreign body response, which shows promise to accelerate the clinical development of this new generation of biomedical devices. PMID: 21488813 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | How Matrix Properties Control the Self-Assembly and Maintenance of Tissues. Ann Biomed Eng. 2011 Apr 14; Authors: Reinhart-King CA The mechanism by which cells organize into tissues is fundamental to developmental biology and tissue engineering. Likewise, the disruption of cellular order within tissues is a hallmark of many diseases including cancer and atherosclerosis. Tissue formation is regulated, in part, by a balance between cell-cell cohesion and cell-extracellular matrix (ECM) adhesion. Here, experiments and approaches to alter this balance are discussed, and the nature of this balance in the formation of microvasculature is explored. Using matrices of tailored stiffness and matrix presentation, the role of the mechanical properties and ligand density in angiogenesis has been investigated. Decreasing cell-matrix adhesion by either reducing matrix stiffness or matrix ligand density induces the self-assembly of endothelial cells into network-like structures. These structures are stabilized by the polymerization of the extracellular matrix protein fibronectin. When fibronectin polymerization is inhibited, network formation does not occur. Interestingly, this interplay between substrate mechanics, ECM assembly, and tissue self-assembly is not limited to endothelial cells and has been observed in other cell types as well. These results suggest novel approaches to foster stable cell-cell adhesion and engineer tissues. PMID: 21491153 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal stem cells and bone regeneration: Current status. Injury. 2011 Apr 11; Authors: Jones E, Yang X The enhancement of bone regeneration with biological agents including osteogenic growth factors and mesenchymal stem cells (MSCs) is becoming a clinical reality. Many exciting findings have been obtained following MSC implantation in animal models, and the data demonstrating their clinical efficacy in humans are promising. The overwhelming majority of experimental work has been performed with MSCs "amplified"in vitro. The nature of native MSCs in skeletal tissues however, remains poorly understood. This review summarizes recent findings pertaining to the definition and characterisation of MSCs in skeletal tissues and discusses the mechanisms of their actions in regenerating of bone in vivo. In respect to traditional tissue engineering paradigm, we bring together literature showing that the ways MSCs are extracted, expanded and implanted can considerably affect bone formation outcomes. Additionally, we discuss current animal models used in MSC research and highlight recent experiments showing important contribution of the host, and not only donor MSCs, in bone tissue formation. This knowledge provides a platform for novel therapy development for bone regeneration based on pharmacologically manipulated endogenous MSCs. PMID: 21489533 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue engineering approaches for bone repair: Concepts and evidence. Injury. 2011 Apr 11; Authors: Schroeder JE, Mosheiff R Over the last decades, the medical world has advanced dramatically in the understanding of fracture repair. The three components needed for fracture healing are osteoconduction, osteoinduction and osteogenesis. With newly designed scaffolds, ex vivo produced growth factors and isolated stem cells, most of the challenges of critical size bone defects have been resolved in vitro, and in some cases in animal models as well. However, there are still challenges needed to be overcome before these technologies can be fully converted from the bench to the bedside. These technological and biological advancements need to be converted to mass production of affordable products that can be used in every part of the world. Vascularity, full substation of scaffolds by native bone, and bio-safety are the three most critical steps to be challenged before reaching the clinical setting. PMID: 21489529 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Ultra-minimally invasive local immune cell therapy and regenerative therapy by multi-piercing surgery for abdominal solid tumor: therapeutic simulation by natural orifice translumenal endoscopic surgery-assisted needlescopic surgery using 3-mm diameter robots. J Hepatobiliary Pancreat Sci. 2011 Apr 13; Authors: Ohdaira T, Tsutsumi N, Xu H, Mori M, Uemura M, Ieiri S, Hashizume M BACKGROUND/PURPOSE: We have invented multi-piercing surgery (MPS) which could potentially solve the triangular formation loss and device clashing which occur in single-port surgery (SPS), as well as restricted visual field, organ damage by needle-type instruments, and impaired removal of a resected organ from the body which occur in needlescopic surgery (NS). MPS is natural orifice translumenal endoscopic surgery (NOTES)-assisted NS. We used 3-mm diameter robots as needle-type instruments for MPS to examine the possibility of local immune cell therapy and regenerative therapy using stem cells for pancreatic cancer. METHODS: In MPS using two robots, the therapeutic cell suspension was injected into a target region of pancreas in two pigs. Both retention of a capsule of liquid cell suspension and invasive level were evaluated. RESULTS: Triangular formation could be ensured. The use of small-diameter robots allowed (1) the surgical separation of the pancreas and the retroperitoneum, and (2) the formation of the capsule containing the immune cell and stem cell suspension. The endoscope for NOTES provided a clear visual field and also assisted the removal of a resected organ from the body. The visual field of the endoscope could be oriented well by using an electromagnetic navigation system. CONCLUSIONS: MPS using small-diameter robots could potentially solve the issues inherent in SPS and NS and could allow minimally invasive local immune cell and stem cell therapy. PMID: 21487759 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Normothermic Ex Vivo Lung Perfusion in Clinical Lung Transplantation. N Engl J Med. 2011 Apr 14;364(15):1431-1440 Authors: Cypel M, Yeung JC, Liu M, Anraku M, Chen F, Karolak W, Sato M, Laratta J, Azad S, Madonik M, Chow CW, Chaparro C, Hutcheon M, Singer LG, Slutsky AS, Yasufuku K, de Perrot M, Pierre AF, Waddell TK, Keshavjee S Background More than 80% of donor lungs are potentially injured and therefore not considered suitable for transplantation. With the use of normothermic ex vivo lung perfusion (EVLP), the retrieved donor lung can be perfused in an ex vivo circuit, providing an opportunity to reassess its function before transplantation. In this study, we examined the feasibility of transplanting high-risk donor lungs that have undergone EVLP. Methods In this prospective, nonrandomized clinical trial, we subjected lungs considered to be high risk for transplantation to 4 hours of EVLP. High-risk donor lungs were defined by specific criteria, including pulmonary edema and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PO(2):FIO(2)) less than 300 mm Hg. Lungs with acceptable function were subsequently transplanted. Lungs that were transplanted without EVLP during the same period were used as controls. The primary end point was primary graft dysfunction 72 hours after transplantation. Secondary end points were 30-day mortality, bronchial complications, duration of mechanical ventilation, and length of stay in the intensive care unit and hospital. Results During the study period, 136 lungs were transplanted. Lungs from 23 donors met the inclusion criteria for EVLP; in 20 of these lungs, physiological function remained stable during EVLP and the median PO(2):FIO(2) ratio increased from 335 mm Hg in the donor lung to 414 and 443 mm Hg at 1 hour and 4 hours of perfusion, respectively (P<0.001). These 20 lungs were transplanted; the other 116 lungs constituted the control group. The incidence of primary graft dysfunction 72 hours after transplantation was 15% in the EVLP group and 30% in the control group (P=0.11). No significant differences were observed for any secondary end points, and no severe adverse events were directly attributable to EVLP. Conclusions Transplantation of high-risk donor lungs that were physiologically stable during 4 hours of ex vivo perfusion led to results similar to those obtained with conventionally selected lungs. (Funded by Vitrolife; ClinicalTrials.gov number, NCT01190059 .). PMID: 21488765 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | CDK4 and cyclin D1 allow human myogenic cells to recapture growth property without compromising differentiation potential. Gene Ther. 2011 Apr 14; Authors: Shiomi K, Kiyono T, Okamura K, Uezumi M, Goto Y, Yasumoto S, Shimizu S, Hashimoto N In vitro culture systems of human myogenic cells contribute greatly to elucidation of the molecular mechanisms underlying terminal myogenic differentiation and symptoms of neuromuscular diseases. However, human myogenic cells have limited ability to proliferate in culture. We have established an improved immortalization protocol for human myogenic cells derived from healthy and diseased muscles; constitutive expression of mutated cyclin-dependent kinase 4, cyclin D1 and telomerase immortalized human myogenic cells. Normal diploid chromosomes were preserved after immortalization. The immortalized human myogenic cells divided as rapidly as primary human myogenic cells during the early passages, and underwent myogenic, osteogenic and adipogenic differentiation under appropriate culture conditions. The immortalized cells contributed to muscle differentiation upon xenotransplantation to immunodeficient mice under conditions of regeneration following muscle injury. We also succeeded in immortalizing cryopreserved human myogenic cells derived from Leigh disease patients following primary culture. Forced expression of the three genes shortened their cell cycle to <30 h, which is similar to the doubling time of primary cultured human myogenic cells during early passages. The immortalization protocol described here allowed human myogenic cells to recapture high proliferation activity without compromising their differentiation potential and normal diploidy.Gene Therapy advance online publication, 14 April 2011; doi:10.1038/gt.2011.44. PMID: 21490680 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Menopausal status affects the susceptibility of stored RBCs to mechanical stress. Vox Sang. 2011 May;100(4):418-421 Authors: Raval JS, Waters JH, Seltsam A, Scharberg EA, Richter E, Kameneva MV, Yazer MH The mechanical fragility index (MFI) is an in vitro measure of sublethal injury to RBCs. In our previous experiments, we demonstrated that an increase in sublethal injury (increasing MFI) was a component of the RBC storage lesion, and that the MFI was significantly higher amongst the RBC units from male donors compared to pre-menopausal female donors during storage. It was hypothesized that hormonal or menstrual factors contributed to this difference. In this study, we found that RBC units donated by post-menopausal women demonstrated an MFI that was significantly higher than those donated by pre-menopausal women throughout storage. PMID: 21488881 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Clinical tolerance in allogeneic hematopoietic stem cell transplantation. Immunol Rev. 2011 May;241(1):145-163 Authors: Roncarolo MG, Gregori S, Lucarelli B, Ciceri F, Bacchetta R Summary: Allogeneic hematopoietic stem cell transplantation (HSCT) has been a curative therapeutic option for a wide range of immune hematologic malignant and non-malignant disorders including genetic diseases and inborn errors. Once in the host, allogeneic transplanted cells have not only to ensure myeloid repopulation and immunological reconstitution but also to acquire tolerance to host human leukocyte antigens via central or peripheral mechanisms. Peripheral tolerance after allogeneic HSCT depends on several regulatory mechanisms aimed at blocking alloimmune reactivity while preserving immune responses to pathogens and tumor antigens. Patients transplanted with HSCT represent an ideal model system in humans to identify and characterize the key cellular and molecular players underlying these mechanisms. The knowledge gained from these studies has allowed the development of novel therapeutic strategies aimed at inducing long-term peripheral tolerance, which can be applicable not only in allogeneic HSCT but also in autoimmune diseases and solid-organ transplantation. In the present review, we describe Type 1 regulatory T cells, initially discovered and characterized in chimeric patients transplanted with human leukocyte antigen-mismatched HSCT, and how their presence correlates to tolerance induction and maintenance. Furthermore, we summarize different cell therapy approaches with regulatory T cells, designed to facilitate tolerance induction, minimizing pharmaceutical interventions. PMID: 21488896 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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