|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Long term in vivo MRI tracking of endothelial progenitor cells transplanted in rat ischemic limbs and their angiogenic potential. Tissue Eng Part A. 2011 Apr 6; Authors: Agudelo CA, Tachibana Y, Noboru T, Iida H, Yamaoka T Stem cell therapy has been used to repair ischemic tissues in the limbs, in myocardial infarctions and in the brain. To understand the mechanisms of healing, a contrast agent capable of inducing sufficient magnetic resonance contrast would be useful in providing fundamental information about the cell migration and incorporation into the ischemic tissue. An MRI contrast agent composed of dextran and gadolinium chelate was synthesized. Hydroxyl groups of dextran were activated with 1,1'-carbonylbis-1H-imidazole and reacted with propanediamine to obtain aminated dextran. This modified polymer was then reacted with mono-N-succinimidyl 1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetate and then with FITC, and finally reacted with gadolinium chloride solution (Dex-DOTA-Gd3+). Endothelial progenitor cells (EPCs) were selected as a stem cell model for MRI tracking. Cells were isolated from the bone marrow harvested from the femurs and tibias of rats. Dex-DOTA-Gd3+ was then introduced into the EPCs by electroporation. The intracellular stability and cytotoxicity of Dex-DOTA-Gd3+ were evaluated in vitro. Dex-DOTA-Gd3+-labeled EPCs were transplanted into a rat model of ischemic limb, and MR images were acquired. Dex-DOTA-Gd3+ was found to efficiently label EPCs over a long duration without significant cytotoxicity. This provides an MR signal sufficient for tracking the EPCs intramuscularly injected into the limb. PMID: 21466415 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts. Biochem Biophys Res Commun. 2011 Apr 4; Authors: Eom YW, Lee JE, Yang MS, Jang IK, Kim HE, Lee DH, Kim YJ, Park WJ, Kong JH, Shim KY, Lee JI, Kim HS Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear. We investigated the myogenic phases of human adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells. In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1 day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6 days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step. Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation. Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin. PMID: 21473854 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Avascular Necrosis of the Hip - Diagnosis and Treatment.] Z Orthop Unfall. 2011 Mar;149(2):231-242 Authors: Drescher W, Pufe T, Smeets R, Eisenhart-Rothe RV, Jäger M, Tingart M Femoral head necrosis is an ischaemic bone necrosis of traumatic or nontraumatic pathogenesis which can lead to hip joint destruction in young age. It is today the indication for 10 % of all the total hip joint replacements. Known aetiologies of nontraumatic femoral head necrosis are alcoholism, steroids, sickle cell anaemia, caisson, and Gaucher's disease. Further risk factors are chemotherapy, chronic inflammatory bowel disease, systemic lupus erythematosus, and multiple sclerosis, in which also steroids are involved. Gravidity is another risk factor, but still idiopathic pathogenesis is found. In diagnosis, the ARCO-classification of the Association for the Research of Osseous Circulation is essential. While stage 0 can only be found histologically, the reversible early stage 1 shows MR signal changes. In the irreversible early stage 2, first native x-ray changes are seen as lower radiolucency reflects new bone apposition on dead trabeculae. In stage 3, subchondral fracture follows, and in stage 4 secondary arthritis of the hip. Established therapy in stage 1 is core decompression, physiotherapy, and more and more also bisphosphonates. Sufficient data to support extracorporeal shock wave therapy are still lacking. Stem cell therapy seems to be a promising new therapy method in stage 2. In stage 2 and 3 mainly proximal femoral osteotomies and (non)vascularised bone transplantation are performed. In stage 4, depending on size and location of the necrotic zone and pathology of the adjacent bone, resurfacing or short stem hip arthroplasty can be performed. However, conventional THA is still golden standard. The problem and challenge, however, is the often young patient age in femoral head necrosis. Especially chemotherapy-associated osteonecrosis in leukaemia is found in patients in their second decade of life. Therefore, the hip should be preserved as long as possible. PMID: 21469042 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts. Biochem Biophys Res Commun. 2011 Apr 4; Authors: Eom YW, Lee JE, Yang MS, Jang IK, Kim HE, Lee DH, Kim YJ, Park WJ, Kong JH, Shim KY, Lee JI, Kim HS Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear. We investigated the myogenic phases of human adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells. In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1 day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6 days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step. Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation. Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin. PMID: 21473854 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Blocking HIF1α Activity Eliminates Hematological Cancer Stem Cells. Cell Stem Cell. 2011 Apr 8;8(4):354-6 Authors: Lam BS, Adams GB Selective targeting of cancer stem cells (CSCs) has the potential to prevent cancer relapse. Wang et al. (2011) report that hypoxia-inducible factor 1α (HIF1α) represses Notch signaling to maintain CSC subsets from lymphoma, and that blocking HIF1α activity eliminates lymphoma and human acute myeloid leukemia (AML) CSCs. PMID: 21474097 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A repair "kit" for the infarcted heart. Cell Stem Cell. 2011 Apr 8;8(4):350-2 Authors: Mignone JL, Murry CE Transplanted, c-kit expressing marrow-derived progenitors can enhance the function of an infarcted heart, but the mechanism remains unclear. In this issue of Cell Stem Cell, Loffredo et al. (2011) provide evidence that hematopoietic precursors do not differentiate into new cardiomyocytes but, rather, stimulate production of new cardiomyocytes from endogenous progenitors. PMID: 21474095 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Dopamine Controls Neurogenesis in the Adult Salamander Midbrain in Homeostasis and during Regeneration of Dopamine Neurons. Cell Stem Cell. 2011 Apr 8;8(4):426-33 Authors: Berg DA, Kirkham M, Wang H, Frisén J, Simon A Appropriate termination of regenerative processes is critical for producing the correct number of cells in tissues. Here we provide evidence for an end-product inhibition of dopamine neuron regeneration that is mediated by dopamine. Ablation of midbrain dopamine neurons leads to complete regeneration in salamanders. Regeneration involves extensive neurogenesis and requires activation of quiescent ependymoglia cells, which express dopamine receptors. Pharmacological compensation for dopamine loss by L-dopa inhibits ependymoglia proliferation and regeneration in a dopamine receptor-signaling-dependent manner, specifically after ablation of dopamine neurons. Systemic administration of the dopamine receptor antagonist haloperidol alone causes ependymoglia proliferation and the appearance of excessive number of neurons. Our data show that stem cell quiescence is under dopamine control and provide a model for termination once normal homeostasis is restored. The findings establish a role for dopamine in the reversible suppression of neurogenesis in the midbrain and have implications for regenerative strategies in Parkinson's disease. PMID: 21474106 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Donation of embryos for human development and stem cell research. Cell Stem Cell. 2011 Apr 8;8(4):360-2 Authors: Kalista T, Freeman HA, Behr B, Pera RR, Scott CT Using donated human embryos for scientific research raises ethical questions about the donation process. We describe a two-stage consent process designed to help couples make informed decisions about embryo disposition. This consent methodology minimizes conflict of interest, respects patient choice, and provides a much-needed resource to patients and the research community. PMID: 21474099 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Genetic influences on stress urinary incontinence. Curr Opin Urol. 2010 Jul;20(4):291-5 Authors: McKenzie P, Rohozinski J, Badlani G The purpose of this review is to summarize the current evidence for the genetic basis of stress urinary incontinence (SUI). PMID: 21475072 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine: DIY eye. Nature. 2011 Apr 7;472(7341):42-3 Authors: Ali RR, Sowden JC PMID: 21475187 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Bioengineering in the oral cavity: insights from articular cartilage tissue engineering. Int J Oral Maxillofac Implants. 2011;26 Suppl:11-9; discussion 20-4 Authors: Duraine G, Hu J, Athanasoiu K Cartilage failure in diarthrodial joints results in pain and a reduction in quality of life. The goal of cartilage tissue engineering is to replace or regenerate these mechanically loaded tissues to restore function to the joint. Recent advances in the authors' laboratory have resulted in the production of cartilage and fibrocartilage with clinically relevant properties. A review of salient results will constitute the bulk of this manuscript. After providing a brief background of the clinical problem, this review will highlight several specific tissue engineering tools. The approaches used to produce mechanically functional cartilage through tissue engineering have several parallels to the problems faced in osseointegration, eg, the need for mechanically appropriate tissues at the implantation site. The discussion that follows will focus on how approaches developed in identifying alternative cell sources and various exogenous stimuli for producing new cartilage may be applicable to osseointegration. PMID: 21464997 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue engineering with recombinant human platelet-derived growth factor BB for implant site development. Compend Contin Educ Dent. 2011 Mar;32(2):18, 20-7; quiz 28, 40 Authors: Nevins ML, Reynolds MA Currently, PDGF-BB is FDA-approved for periodontal regeneration as part of a dental bone-filling device only. Although this device uses beta-TCP as the scaffold carrier, there has been considerable clinical interest in combining this growth factor with other bone replacement grafts, particularly bone allografts. This article reports on clinical experiences using rhPDGF-BB with bone allografts for implant site development. After careful evaluation of clinical parameters and consideration of current and emerging evidence, the off-label use of rhPDGF-BB was determined in the following case reports to be consistent with good clinical practice and in the patient's best interest. Clinical, radiographic, and histologic observations from the following selected cases are presented to illustrate treatment outcomes achieved using this combination strategy: ridge preservation for extraction sockets with alveolar wall defects; ridge preservation for extraction sockets minimally invasive techniques; lateral ridge augmentation; and sinus augmentation. All of the cases presented and reviewed were surgically managed using 0.5 ml of 0.3 mg/ml of rhPDGF delivered using a particulate bone allograft (FDBA or DFDBA) as a scaffold. Controlled clinical trials are necessary to establish the relative effectiveness of rhPDGF-BB combined with different mammalian scaffolds for alveolar augmentation. PMID: 21473297 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts. Biochem Biophys Res Commun. 2011 Apr 4; Authors: Eom YW, Lee JE, Yang MS, Jang IK, Kim HE, Lee DH, Kim YJ, Park WJ, Kong JH, Shim KY, Lee JI, Kim HS Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear. We investigated the myogenic phases of human adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells. In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1 day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6 days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step. Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation. Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin. PMID: 21473854 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | An ex vivo continuous passive motion model in a porcine knee for assessing primary stability of cell-free collagen gel plugs. BMC Musculoskelet Disord. 2010;11:283 Authors: Efe T, Schofer MD, Füglein A, Timmesfeld N, Fuchs-Winkelmann S, Stein T, El-Zayat BF, Paletta JR, Heyse TJ Primary stability of cartilage repair constructs is of the utmost importance in the clinical setting but few continuous passive motion (CPM) models are available. Our study aimed to establish a novel ex vivo CPM animal model and to evaluate the required motion cycles for testing the mechanical properties of a new cell-free collagen type I gel plug (CaReS®-1S). PMID: 21159196 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Controlled delivery of glial cell line-derived neurotrophic factor enhances motor nerve regeneration. J Hand Surg Am. 2010 Dec;35(12):2008-17 Authors: Moore AM, Wood MD, Chenard K, Hunter DA, Mackinnon SE, Sakiyama-Elbert SE, Borschel GH To determine the effect of a motor-specific neurotrophic factor, glial-derived neurotrophic factor (GDNF) on motor nerve regeneration. PMID: 21035963 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Perspectives in regeneration and tissue engineering of peripheral nerves. Ann Anat. 2011 Mar 12; Authors: Raimondo S, Fornaro M, Tos P, Battiston B, Giacobini-Robecchi MG, Geuna S Peripheral nerve injury is a common casualty and although peripheral nerve fibers retain a considerable regeneration potential also in the adult, recovery is usually rather poor, especially in case of large nerve defects. The aim of this paper is to address the perspectives in regeneration and tissue engineering after peripheral nerve injury by reviewing the relevant experimental studies in animal models. After a brief overview of the morphological changes related to peripheral nerve injury and regeneration, the paper will address the evolution of peripheral nerve tissue engineering with special focus on transplantation strategies, from organs and tissues to cells and genes, that can be carried out, particularly in case of severe nerve lesions with substance loss. Finally, the need for integrated research which goes beyond therapeutic strategies based on single approaches is emphasized, and the importance of bringing together the various complimentary disciplines which can contribute to the definition of effective new strategies for regenerating the injured peripheral nerve is outlined. PMID: 21474294 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Several types of soft tissue sarcomas originate from the malignant transformation of adipose tissue-derived stem cells. Mol Med Report. 2010 May-Jun;3(3):441-8 Authors: Chen H, Zhang S, Wen JC, Zheng JK, Chen Q, Li WY, Wang PP, Ma L, Huang TH, Huang G, Yang LY The cellular origin of soft tissue sarcomas (STSs) is not fully understood. The cancer stem cell hypothesis presumes that tumors originate from the malignant transformation of stem cells. As a type of multipotent stem cell, adipose tissue-derived stromal/stem cells (ADSCs), which possess an unexpected degree of plasticity and often reside in other tissues, may represent a potential source of soft tissue sarcoma. To ascertain whether ADSCs are responsible for the formation of STSs, ADSCs from mice were cultured and treated with 3-methycholanthrene to derive transformed cells. These transformed ADSCs were then injected subcutaneously into immunodeficient mice to test their tumorigenic potential. We found that they generated several types of STSs, including synovial sarcoma, malignant fibrous histiocytoma and fibrosarcoma. This is the first study to report that ADSCs may be the potential initiating cells for synovial sarcoma. Our findings indicate that STSs might originate from malignantly transformed ADSCs. PMID: 21472259 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Optimised production of multifunctional microfibres by microfluidic chip technology for tissue engineering applications. Lab Chip. 2011 Apr 6; Authors: Mazzitelli S, Capretto L, Carugo D, Zhang X, Piva R, Nastruzzi C This paper describes a method for the production of alginate microfibres using glass-based microfluidic chips fabricated by a photolithography-wet etching procedure. The main focus of the work is the fabrication of a cell containing multifunctional microfibres which have great potential for applications in drug release formulations and tissue engineering scaffolds (to guide the regeneration of tissues in predefined sizes and shapes) providing cell structural support and immunoisolation. The key parameters, which critically influence the formation of microfibres and their geometries, were identified by a classical intuitive approach COST (Changing One Separate factor a Time). In particular, their effects on the microfibre diameter were investigated, which are directly associated with their functionalities relating to the implantation site, the nutrient availability and diffusion/transport of oxygen, essential nutrients, growth factors, metabolic waste and secretory products. The interplay between the alginate solution concentration, pumping rate and gelling bath concentration in controlling the diameter of the produced microfibres was investigated with a statistical approach by means of a "design of the experiments" (DoEs) optimization and screening. Finally, the processing impacts on cell viability, the cellular effect of wall thickness consistency and the spatial distribution of cells within the alginate microfibre were examined. We provide an approach for the production of alginate microfibres with controlled shape and content, which could be further developed for scaling up and working towards FDA approval. PMID: 21472178 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Nutrient diffusion and simple n(th)-order consumption in regenerative tissue and biocatalytic sensors. Biophys Chem. 2011 Feb 23; Authors: Belfiore LA, Floren ML, Volpato FZ, Paulino AT, Belfiore CJ This contribution addresses intra-tissue molar density profiles for nutrients, oxygen, growth factors, and other essential ingredients that anchorage-dependent cells require for successful proliferation on biocompatible surfaces. One-dimensional transient and steady state models of the reaction-diffusion equation are solved to correct a few deficiencies in the first illustrative example of diffusion and zeroth-order rates of consumption in tissues with rectangular geometry, as discussed in Ref. [(Griffith and Swartz, 2006) 1]. The functional form of the molar density profile for each species depends on geometry and the magnitude of the species-specific intra-tissue Damköhler number. The tissue's central core is reactant starved at high consumption rates and low rates of intra-tissue diffusion when the Damköhler number exceeds its geometry-sensitive critical value. Ideal tissue engineering designs avoid the diffusion-limited regime such that attached cells are exposed to all of the ingredients required for proliferation everywhere within a regenerative matrix. Analytical and numerical molar density profiles that satisfy the unsteady state modified diffusion equation with pseudo-homogeneous n(th)-order rates of intra-tissue consumption (i.e., n=0,1,2) allow one to (i) predict von Kármán-Pohlhausen mass transfer boundary layer thicknesses, measured inward from the external biomaterial surface toward its central core, and, most importantly, (ii) estimate the time required to achieve steady state conditions for regenerative tissue growth and biocatalytic sensing. PMID: 21470767 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Serum Calcium-decreasing Factor, Caldecrin, Ameliorates Muscular Dystrophy in dy/dy Mice. In Vivo. 2011 Mar-Apr;25(2):157-63 Authors: Tomomura M, Fujii T, Sakagami H, Tomomura A Calcium signaling is important in muscular cells and abnormal Ca(2+) handling results in muscle damage. Caldecrin is a serum calcium-decreasing factor purified from pancreas. It is a chymotrypsin-type secretory protease, whereas the serum calcium-decreasing activity does not depend on its protease activity. Here, we evaluated the effect of caldecrin on dystrophia muscularis (dy/dy) mice. PMID: 21471529 [PubMed - in process] | | | | | | | | | |  | |  | |  |
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