|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | Inclusion of basic adipose tissue engineering research in a lipofilling procedure. Plast Reconstr Surg. 2011 Mar;127(3):80e-2e Authors: Doornaert MA, Blondeel PN, Stillaert FB PMID: 21364400 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Do stem cell-derived islets represent a commercially viable treatment for Type 1 and 2 diabetes? Regen Med. 2010 Nov;5(6):839-42 Authors: Wong AL, Nierras CR PMID: 21082882 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal stem cells for the treatment of neurodegenerative disease. Regen Med. 2010 Nov;5(6):933-46 Authors: Joyce N, Annett G, Wirthlin L, Olson S, Bauer G, Nolta JA Mesenchymal stem cells/marrow stromal cells (MSCs) present a promising tool for cell therapy, and are currently being tested in US FDA-approved clinical trials for myocardial infarction, stroke, meniscus injury, limb ischemia, graft-versus-host disease and autoimmune disorders. They have been extensively tested and proven effective in preclinical studies for these and many other disorders. There is currently a great deal of interest in the use of MSCs to treat neurodegenerative diseases, in particular for those that are fatal and difficult to treat, such as Huntington's disease and amyotrophic lateral sclerosis. Proposed regenerative approaches to neurological diseases using MSCs include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation into the brain, MSCs promote endogenous neuronal growth, decrease apoptosis, reduce levels of free radicals, encourage synaptic connection from damaged neurons and regulate inflammation, primarily through paracrine actions. MSCs transplanted into the brain have been demonstrated to promote functional recovery by producing trophic factors that induce survival and regeneration of host neurons. Therapies will capitalize on the innate trophic support from MSCs or on augmented growth factor support, such as delivering brain-derived neurotrophic factor or glial-derived neurotrophic factor into the brain to support injured neurons, using genetically engineered MSCs as the delivery vehicles. Clinical trials for MSC injection into the CNS to treat traumatic brain injury and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of neurodegenerative disorders are discussed. PMID: 21082892 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | p53: guardian of reprogramming. Cell Cycle. 2010 Oct 1;9(19):3887-91 Authors: Menendez S, Camus S, Izpisua Belmonte JC The reprogramming of somatic cells to induced pluripotent stem (iPS) cells is one of the major discoveries of recent years. The development and application of patient specific iPS lines could potentially revolutionise cell-based therapy, facilitating the treatment of a wide range of diseases. Despite the numerous technological advancements in the field, an in-depth mechanistical understanding of the pathways involved in reprogramming is still lacking. Several groups have recently provided a mechanistical insight into the role of the p53 tumour suppressor pathway in reprogramming. The repercussions of these findings are profound and reveal an unexpected role of p53 as a "guardian of reprogramming", ensuring genomic integrity during reprogramming at the cost of a reduced efficiency of the process. Here we analyse the latest findings in the field and discuss their relevance for future applications of iPS cell technology. PMID: 20948296 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Carbon nanotubes as a scaffold for spermatogonial cell maintenance. J Biomed Nanotechnol. 2010 Dec;6(6):710-7 Authors: Rafeeqi T, Kaul G Carbon nanotubes (CNTs) are viewed as a class of nanomaterials with high potential for many biomedical applications due to their unique properties. One of the prospective bio-application of CNTs is in the area of tissue engineering as a scaffold for cell culture. Supporting the use of CNTs as scaffold in tissue engineering a few cell types have been successfully grown on it but no report for any germline cell. In the present study, the in vitro maintenance of spermatogonial cells on carbon nanotube scaffold has been evaluated for the first time. Protein adsorption on the CNT scaffolds along with other substrates has also been evaluated because it is very likely that adsorbed proteins in serum influence the properties for the cell growth. Microscopic analysis (Light and SEM) showed that cells maintain their proper shape and adhered on all CNT scaffolds during in vitro culture. It was observed that the cells were maintained for at least 21 days on all CNT scaffolds compared to the positive control (Sertoli feeder layer). The results express a degree of biocompatibility between spermatogonial cells and CNTs and the possibility for CNTs to be used as substratum for in vitro growth of these cells. PMID: 21361137 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal stem cells from murine amniotic fluid as a model for preclinical investigation. Arch Iran Med. 2011 Mar;14(2):96-103 Authors: Baghaban Eslaminejad M, Jahangir S, Aghdami N Despite the suitability of a mouse model for preclinical investigations; little is known regarding mesenchymal stem cells derived from murine amniotic fluid. This is the subject of the present study. PMID: 21361715 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Sustained-release adrenomedullin ointment accelerates wound healing of pressure ulcers. Regul Pept. 2011 Feb 25; Authors: Harada K, Yamahara K, Ohnishi S, Otani K, Kanoh H, Ishibashi-Ueda H, Minamino N, Kangawa K, Nagaya N, Ikeda T Pressure ulcers are one of the most common complications in elderly, incontinent or paralyzed patients. For the healing of pressure ulcers, the development of granulation tissue and reepithelialization are required. Adrenomedullin (AM), an endogenous vasodilator peptide, is reported to stimulate the proliferation and migration of various cells including endothelial cells, fibroblasts and keratinocytes. Therefore, we hypothesized that AM might accelerate the healing process of pressure ulcers in which these cells were involved. We developed a sustained-release ointment containing human recombinant AM, and applied it in a mouse model of pressure ulcer twice a day for 14days. Human AM was efficiently absorbed in wound area, but its blood concentration was negligible. AM ointment significantly reduced the wound area on day 5 to 7 after injury. In addition, AM ointment accelerated the formation of granulation tissue and angiogenesis as well as lymphangiogenesis after 7days of treatment. Immunological analysis revealed that Ki-67-positive proliferating cells in granulation tissue expressed AM receptors. In summary, sustained-released AM significantly improved wound healing of pressure ulcers through acceleration of granulation and induction of angiogenesis and lymphangiogenesis. Therefore, sustained-release AM ointment may be a novel therapeutic agent for pressure ulcers. PMID: 21362442 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Acute skeletal injury is necessary for human adipose-derived stromal cell-mediated calvarial regeneration. Plast Reconstr Surg. 2011 Mar;127(3):1118-29 Authors: Levi B, James AW, Nelson ER, Peng M, Wan DC, Commons GW, Lee M, Wu B, Longaker MT : Studies have demonstrated that human adipose-derived stromal cells (ASCs) are able to repair acute calvarial injuries. The more clinically relevant repair of an established skeletal defect, however, has not been addressed. The authors sought to determine whether human ASCs could heal chronic (established) calvarial defects. PMID: 21364415 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Myc transcription factors: key regulators behind establishment and maintenance of pluripotency. Regen Med. 2010 Nov;5(6):947-59 Authors: Smith K, Dalton S The interplay between transcription factors, epigenetic modifiers, chromatin remodelers and miRNAs form the foundation of a complex regulatory network required for establishment and maintenance of the pluripotent state. Recent work indicates that Myc transcription factors are essential elements of this regulatory system. However, despite numerous studies, aspects of how Myc controls self-renewal and pluripotency remain obscure. This article reviews evidence supporting the placement of Myc as a central regulator of the pluripotent state and discusses possible mechanisms of action. PMID: 21082893 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Safely modulating the immune system in regenerative medicine. Cell Stem Cell. 2011 Mar 4;8(3):246-7 Authors: Pera MF The destruction of pluripotent stem cell-derived grafts by the host immune system presents a significant barrier to clinical translation of cell therapies. Pearl et al. (2011) report in this issue of Cell Stem Cell that a brief, nontoxic immunosuppressive regimen, achieved by blockade of leucocyte costimulatory pathways, may overcome this problem. PMID: 21362563 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | HA/CD44 interactions as potential targets for cancer therapy. FEBS J. 2011 Mar 1; Authors: Misra S, Heldin P, Hascall VC, Karamanos NK, Skandalis SS, Markwald RR, Ghatak S It is becoming increasingly clear that signals generated in tumor microenvironments are crucial to tumor cell behavior, such as, survival progression, and metastasis. The establishment of these malignant behaviors requires that tumor cells acquire novel adhesion and migration properties to detach from their original sites for localizing into distant organs. CD44, an adhesion/homing molecule is a major receptor for the glycosaminoglycan hyaluronan, which is one of the major components of the tumor extracellular matrix (ECM). CD44, a multi structural and multifunctional molecule, detects changes in ECM components, and thus is well positioned to provide appropriate responses to changes in the microenvironment, i.e. engagement in cell-cell and cell-ECM interactions, cell traffic, lymph node homing, and presentation of growth factors/cytokines/chemokines to co-ordinate signaling events that enable the cell responses that change in the tissue environment. The potential involvement of CD44variants (CD44v), especially CD44v4-v7 and CD44v6-v9 in tumor progression was confirmed for many tumor types in numerous clinical studies. Down regulation of the standard CD44 isoform (CD44s) in colon cancer is postulated to result in increased tumorigenicity. CD44v-specific functions could be due to their higher binding affinity for hyaluronan than CD44s. Alternatively, CD44v-specific functions could be due to differences in associating molecules, which may bind selectively to the CD44v exon. This review summarizes how the interaction between hyaluronan and CD44v can serve as a potential target for cancer therapy, in particular how silencing the CD44v can target multiple metastatic tumors. PMID: 21362138 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Graft and host interactions following transplantation of neural stem cells to organotypic striatal cultures. Regen Med. 2010 Nov;5(6):901-17 Authors: Jäderstad LM, Jäderstad J, Herlenius E To investigate neural stem cell (NSC) interactions with striatal tissue following engraftment and the effects of growth factors. PMID: 21082890 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | An efficient method for generation of neural-like cells from adult human bone marrow-derived mesenchymal stem cells. Regen Med. 2010 Nov;5(6):891-900 Authors: Alexanian AR Stem cell-based therapies to repair and replace lost neural cells are a highly promising treatment for CNS diseases. Bone marrow (BM)-derived mesenchymal stem cells (MSCs) have great potential as therapeutic agents against neurological maladies, since they have the ability to differentiate into neural phenotypes and can be readily isolated and expanded for autotransplantation with no risk of rejection. In our previous studies, we demonstrated that neural cells could be efficiently generated from mouse BM-derived MSCs by exposing cells to epigenetic modifiers and a neural environment. The main idea of this approach was the reactivation of pluripotency-associated genes in MSCs before exposing them to neural-inducing factors. PMID: 21082889 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Partial dysferlin reconstitution by adult murine mesoangioblasts is sufficient for full functional recovery in a murine model of dysferlinopathy. Cell Death Dis. 2010 Aug;1(8):e61 Authors: Díaz-Manera J, Touvier T, Dellavalle A, Tonlorenzi R, Tedesco FS, Messina G, Meregalli M, Navarro C, Perani L, Bonfanti C, Illa I, Torrente Y, Cossu G Dysferlin deficiency leads to a peculiar form of muscular dystrophy due to a defect in sarcolemma repair and currently lacks a therapy. We developed a cell therapy protocol with wild-type adult murine mesoangioblasts. These cells differentiate with high efficiency into skeletal muscle in vitro but differ from satellite cells because they do not express Pax7. After intramuscular or intra-arterial administration to SCID/BlAJ mice, a novel model of dysferlinopathy, wild-type mesoangioblasts efficiently colonized dystrophic muscles and partially restored dysferlin expression. Nevertheless, functional assays performed on isolated single fibers from transplanted muscles showed a normal repairing ability of the membrane after laser-induced lesions; this result, which reflects gene correction of an enzymatic rather than a structural deficit, suggests that this myopathy may be easier to treat with cell or gene therapy than other forms of muscular dystrophies. PMID: 21364666 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Carbon monoxide pollution and lung function in urban compared with rural Mongolian children. Respirology. 2011 Mar 1; Authors: Dashdendev B, Fukushima LK, Woo MS, Ganbaatar E, Warburton D SUMMARY AT A GLANCE: FEV(1) was 140% of predicted in rural Mongolian children compared with 100% of predicted in urban children, suggesting that FEV(1) in apparently healthy urban children may not in fact be normal, but may instead reflect the deleterious effects of ambient air pollution, as indicated by three-fold greater ambient CO levels. ABSTRACT: Background and objective: Mongolia is experiencing rapid urbanization, and this presents a unique opportunity to assess the effects of this process on the lung health of children. Methods: Two cross-sectional cohorts of school-age children (5-15 years of age) from the capital (Ulaanbaatar) (n= 116) and a rural district (Tuv Aimag) (n= 108) were studied. Demographic information, exposure to tobacco smoke, and ambient and exhaled CO, as well as FEV(1) and FEF(25-75%) were recorded for each child. Results: Ambient CO levels were three-fold higher in the capital city than in the rural Aimag [0.63 versus 0.21 parts per million (ppm), P < 0.00005], while exhaled CO was two-fold higher (0.94 versus 0.47 ppm, P < 0.00001). Rural Mongolian children were 6 cm shorter on average than urban children. However, when adjusted for age and height, FEV(1) was 140% of predicted in rural children compared with 106% of predicted in urban children (P < 0.00001). There was no significant difference in small airway expiratory flow (FEF(25-75%) ; 104 in urban children, 100 in rural children, P= 0.63). Conclusions: "Normal" FEV(1) was actually 40% higher in rural Mongolian children than in urban children, suggesting that the FEV(1) of apparently healthy children living in urbanized societies may in fact not be normal, but may instead reflect the deleterious effects of air pollution in cities, as indicated by increased levels of both environmental and exhaled CO. PMID: 21362106 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Simulation of an in vitro niche environment that preserves conjunctival progenitor cells. Regen Med. 2010 Nov;5(6):877-89 Authors: Schrader S, Notara M, Tuft SJ, Beaconsfield M, Geerling G, Daniels JT To evaluate a serum-free system where mitotically active subconjunctival fibroblasts were co-cultured with conjunctival epithelial cells to mimic a niche environment for conjunctival progenitor cells. PMID: 21082888 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Optimization of human tendon tissue engineering: peracetic Acid oxidation for enhanced reseeding of acellularized intrasynovial tendon. Plast Reconstr Surg. 2011 Mar;127(3):1107-17 Authors: Woon CY, Pridgen BC, Kraus A, Bari S, Pham H, Chang J : Tissue engineering of human flexor tendons combines tendon scaffolds with recipient cells to create complete cell-tendon constructs. Allogenic acellularized human flexor tendon has been shown to be a useful natural scaffold. However, there is difficulty repopulating acellularized tendon with recipient cells, as cell penetration is restricted by a tightly woven tendon matrix. The authors evaluated peracetic acid treatment in optimizing intratendinous cell penetration. PMID: 21364414 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Eighth IQUAM Consensus Conference Position Statement: Transatlantic Innovations, April 2009. Plast Reconstr Surg. 2011 Mar;127(3):1368-75 Authors: Neuhann-Lorenz C, Fedeles J, Eisenman-Klein M, Kinney B, Cunningham BL : On April 7, 2009, the International Committee for Quality Assurance, Medical Technologies and Devices in Plastic Surgery (IQUAM) issued its 8th Position Statement. IQUAM is a professional medical and scientific organization committed to the surveillance of existing and new technologies and devices in plastic surgery. IQUAM periodically reviews and evaluates updated international literature and studies and scientific data, and recommends standards of treatment for plastic surgery devices and technologies. IQUAM proscribes potentially deleterious use of products, devices, and technologies, or their unintended application or application for unsuitable indications. PMID: 21364439 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Isolation of epiblast stem cells from preimplantation mouse embryos. Cell Stem Cell. 2011 Mar 4;8(3):318-25 Authors: Najm FJ, Chenoweth JG, Anderson PD, Nadeau JH, Redline RW, McKay RD, Tesar PJ Pluripotent stem cells provide a platform to interrogate control elements that function to generate all cell types of the body. Despite their utility for modeling development and disease, the relationship of mouse and human pluripotent stem cell states to one another remains largely undefined. We have shown that mouse embryonic stem (ES) cells and epiblast stem cells (EpiSCs) are distinct, pluripotent states isolated from pre- and post-implantation embryos respectively. Human ES cells are different than mouse ES cells and share defining features with EpiSCs, yet are derived from pre-implantation human embryos. Here we show that EpiSCs can be routinely derived from pre-implantation mouse embryos. The preimplantation-derived EpiSCs exhibit molecular features and functional properties consistent with bona fide EpiSCs. These results provide a simple method for isolating EpiSCs and offer direct insight into the intrinsic and extrinsic mechanisms that regulate the acquisition of distinct pluripotent states. PMID: 21362571 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Electrospun chitosan nanofibers for hepatocyte culture. J Biomed Nanotechnol. 2010 Dec;6(6):658-66 Authors: Feng ZQ, Leach MK, Chu XH, Wang YC, Tian T, Shi XL, Ding YT, Gu ZZ In this study, we developed a method to obtain high surface area nanofiber meshes composed of chitosan of a number of molecular weights. This method required decreasing the viscosity and surface tension of the chitosan solution as well as optimization of the electrospinning parameters such as applied voltage and environmental humidity. These chitosan nanofiber meshes were developed as a culture substrate for hepatocytes. The fibers exhibited a uniform diameter distribution (average diameter: 112 nm) and FTIR results indicate that the chemical structure of chitosan is stable during the electrospinning process. The attachment, morphology and activity of hepatocytes cultured on the chitosan nanofiber meshes were tested. The results showed that the chitosan nanofibers are biocompatible with hepatocytes and that these chitosan nanofiber meshes could be useful tissue culture substrates for various applications, including bioartificial liver-assist devices and tissue engineering for liver regeneration. PMID: 21361130 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Dermal substitute-assisted healing: enhancing stem cell therapy with novel biomaterial design. Arch Dermatol Res. 2011 Mar 2; Authors: Hodgkinson T, Bayat A The use of dermal substitutes is increasingly widespread but the outcomes of substitute-assisted healing remain functionally deficient. Presently, the most successful scaffolds are acellular polymer matrices, prepared through lyophilization and phase separation techniques, designed to mimic the dermal extracellular matrix. The application of scaffolds containing viable cells has proven to be problematic due to short shelf-life, high cost and death of transplanted cells as a result of immune rejection and apoptosis. Recent advances in biomaterial science have made new techniques available capable of increasing scaffold complexity, allowing the creation of 3D microenvironments that actively control cell behaviour. Importantly, it may be possible through these sophisticated novel techniques, including bio-printing and electrospinning, to accurately direct stem cell behaviour. This complex proposal involves the incorporation of cell-matrix, cell-cell, mechanical cues and soluble factors delivered in a spatially and temporally pertinent manner. This requires accurate modelling of three-dimensional stem cell interactions within niche environments to identify key signalling molecules and mechanisms. The application of stem cells within substitutes containing such environments may result in greatly improved transplanted cell viability. Ultimately this may increase cellular organization and complexity of skin substitutes. This review discusses progress made in improving the efficacy of cellular dermal substitutes for the treatment of cutaneous defects and the potential of evolving new technology to improve current results. PMID: 21365208 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Primed for pluripotency. Cell Stem Cell. 2011 Mar 4;8(3):241-2 Authors: Kunath T To date, pluripotent epiblast stem cells (EpiSCs) had only been derived from postimplantation mouse embryos. In this issue of Cell Stem Cell, Najm et al. (2011) demonstrate that EpiSCs can be routinely derived from preimplantation embryos, showing that both human and mouse blastocysts can produce the same class of primed pluripotent cells. PMID: 21362560 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state. Nat Commun. 2011 Mar;2:214 Authors: Patani R, Hollins AJ, Wishart TM, Puddifoot CA, Alvarez S, de Lera AR, Wyllie DJ, Compston DA, Pedersen RA, Gillingwater TH, Hardingham GE, Allen ND, Chandran S A major challenge in neurobiology is to understand mechanisms underlying human neuronal diversification. Motor neurons (MNs) represent a diverse collection of neuronal subtypes, displaying differential vulnerability in different human neurodegenerative diseases. The ability to manipulate cell subtype diversification is critical to establish accurate, clinically relevant in vitro disease models. Retinoid signalling contributes to caudal precursor specification and subsequent MN subtype diversification. Here we investigate the necessity for retinoic acid in motor neurogenesis from human embryonic stem cells. We show that activin/nodal signalling inhibition, followed by sonic hedgehog agonist treatment, is sufficient for MN precursor specification, which occurs even in the presence of retinoid pathway antagonists. Importantly, precursors mature into HB9/ChAT-expressing functional MNs. Furthermore, retinoid-independent motor neurogenesis results in a ground state biased to caudal, medial motor columnar identities from which a greater retinoid-dependent diversity of MNs, including those of lateral motor columns, can be selectively derived in vitro. PMID: 21364553 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Transforming growth factor-β1 phage model peptides isolated from a phage display 7-mer peptide library can inhibit. Chin Med J (Engl). 2011 Feb;124(3):429-35 Authors: Zong XL, Jiang DY, Wang JC, Liu JL, Liu ZZ, Cai JL Transforming growth factor-β1 (TGF-β1) is known to have a role in keloid formation through the activation of fibroblasts and the acceleration of collagen deposition. The objective of this current study was to isolate TGF-β1 phage model peptides from a phage display 7-mer peptide library to evaluate their therapeutic effect on inhibiting the activity of keloid fibroblasts. PMID: 21362346 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Stem and progenitor cell-based therapy in ischaemic heart disease: promise, uncertainties, and challenges. Eur Heart J. 2011 Feb 28; Authors: Tongers J, Losordo DW, Landmesser U In the absence of effective endogenous repair mechanisms after cardiac injury, cell-based therapies have rapidly emerged as a potential novel therapeutic approach in ischaemic heart disease. After the initial characterization of putative endothelial progenitor cells and their potential to promote cardiac neovascularization and to attenuate ischaemic injury, a decade of intense research has examined several novel approaches to promote cardiac repair in adult life. A variety of adult stem and progenitor cells from different sources have been examined for their potential to promote cardiac repair and regeneration. Although early, small-scale clinical studies underscored the potential effects of cell-based therapy largely by using bone marrow (BM)-derived cells, subsequent randomized-controlled trials have revealed mixed results that might relate, at least in part, to differences in study design and techniques, e.g. differences in patient population, cell sources and preparation, and endpoint selection. Recent meta-analyses have supported the notion that administration of BM-derived cells may improve cardiac function on top of standard therapy. At this stage, further optimization of cell-based therapy is urgently needed, and finally, large-scale clinical trials are required to eventually proof its clinical efficacy with respect to outcomes, i.e. morbidity and mortality. Despite all promises, pending uncertainties and practical limitations attenuate the therapeutic use of stem/progenitor cells for ischaemic heart disease. To advance the field forward, several important aspects need to be addressed in carefully designed studies: comparative studies may allow to discriminate superior cell populations, timing, dosing, priming of cells, and delivery mode for different applications. In order to predict benefit, influencing factors need to be identified with the aim to focus resources and efforts. Local retention and fate of cells in the therapeutic target zone must be improved. Further understanding of regenerative mechanisms will enable optimization at all levels. In this context, cell priming, bionanotechnology, and tissue engineering are emerging tools and may merge into a combined biological approach of ischaemic tissue repair. PMID: 21362705 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | LRRK2 Mutant iPSC-Derived DA Neurons Demonstrate Increased Susceptibility to Oxidative Stress. Cell Stem Cell. 2011 Mar 4;8(3):267-80 Authors: Nguyen HN, Byers B, Cord B, Shcheglovitov A, Byrne J, Gujar P, Kee K, Schüle B, Dolmetsch RE, Langston W, Palmer TD, Pera RR Studies of Parkinson's disease (PD) have been hindered by lack of access to affected human dopaminergic (DA) neurons. Here, we report generation of induced pluripotent stem cells that carry the p.G2019S mutation (G2019S-iPSCs) in the Leucine-Rich Repeat Kinase-2 (LRRK2) gene, the most common PD-related mutation, and their differentiation into DA neurons. The high penetrance of the LRRK2 mutation and its clinical resemblance to sporadic PD suggest that these cells could provide a valuable platform for disease analysis and drug development. We found that DA neurons derived from G2019S-iPSCs showed increased expression of key oxidative stress-response genes and α-synuclein protein. The mutant neurons were also more sensitive to caspase-3 activation and cell death caused by exposure to stress agents, such as hydrogen peroxide, MG-132, and 6-hydroxydopamine, than control DA neurons. This enhanced stress sensitivity is consistent with existing understanding of early PD phenotypes and represents a potential therapeutic target. PMID: 21362567 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Short-term immunosuppression promotes engraftment of embryonic and induced pluripotent stem cells. Cell Stem Cell. 2011 Mar 4;8(3):309-17 Authors: Pearl JI, Lee AS, Leveson-Gower DB, Sun N, Ghosh Z, Lan F, Ransohoff J, Negrin RS, Davis MM, Wu JC Embryonic stem cells (ESCs) are an attractive source for tissue regeneration and repair therapies because they can be differentiated into virtually any cell type in the adult body. However, for this approach to succeed, the transplanted ESCs must survive long enough to generate a therapeutic benefit. A major obstacle facing the engraftment of ESCs is transplant rejection by the immune system. Here we show that blocking leukocyte costimulatory molecules permits ESC engraftment. We demonstrate the success of this immunosuppressive therapy for mouse ESCs, human ESCs, mouse induced pluripotent stem cells (iPSCs), human induced pluripotent stem cells, and more differentiated ESC/(iPSCs) derivatives. Additionally, we provide evidence describing the mechanism by which inhibition of costimulatory molecules suppresses T cell activation. This report describes a short-term immunosuppressive approach capable of inducing engraftment of transplanted ESCs and iPSCs, providing a significant improvement in our mechanistic understanding of the critical role costimulatory molecules play in leukocyte activation. PMID: 21362570 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A rabbit model of peripheral compartment syndrome with associated rhabdomyolysis and a regenerative medicine approach for treatment. Tissue Eng Part C Methods. 2011 Mar 1; Authors: Daly K, Wolf MT, Johnson S, Badylak SF Peripheral compartment syndrome (PCS) has a complex etiology, with limited treatment options and high patient morbidity. Animal models of PCS have been hampered by differences in cross-species anatomy, physiology and the relative rarity of the naturally occurring syndrome in animals. In the present study, the combination of saline infusion with intermittent crushing of skeletal muscle consistently caused increased intracompartmental pressure, hypocalemia and hypercreatinine-phophokinasemia, signs diagnostic of PCS. This method was used to evaluate both the standard PCS treatment, specifically a fasciotomy, and a regenerative medicine approach for treatment - consisting of a fasciotomy with local administration of a biologic scaffold material composed of porcine small intestinal submucosa extracellular matrix (SIS-ECM). The use of this SIS-ECM scaffold in conjunction with a fasciotomy was associated with myogenesis and constructive tissue remodeling in the SIS-ECM treated animals. At 1 month and 3 months after treatment innervated muscle tissue was present at the site of injury. No myogenesis was present in the fasciotomy only treated animals. RAM11+ macrophages, which are associated with constructive tissue remodeling, were present within the injury site in the SIS-ECM treated animals at 1 month. The present study provides a reproducible animal model with which to study PCS, and shows the potential of a regenerative medicine approach to PCS treatment. PMID: 21361746 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mining the extracellular matrix for tissue engineering applications. Regen Med. 2010 Nov;5(6):961-70 Authors: Pradhan S, Farach-Carson MC Tissue engineering is a rapidly evolving interdisciplinary field that aims to regenerate new tissue to replace damaged tissues or organs. The extracellular matrix (ECM) of animal tissues is a complex mixture of macromolecules that play an essential instructional role in the development of tissues and organs. Therefore, tissue engineering approaches rely on the need to present the correct cues to cells, to guide them to maintain tissue-specific functions. Recent research efforts have allowed us to mine various sequences and motifs, which play key roles in these guidance functions, from the ECM. Small conserved peptide sequences mined from ECM molecules can mimic some of the biological functions of their large parent molecules. In addition, these peptide sequences can be linked to various biomaterial scaffolds that can provide the cells with mechanical support to ensure appropriate cell growth and aid the formation of the correct tissue structure. The tissue engineering field will continue to benefit from the advent of these mined ECM sequences which have two major advantages over recombinant ECM molecules: material consistency and scalability. PMID: 21082894 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Lineage restriction of human hepatic stem cells to mature fates is made efficient by tissue-specific biomatrix scaffolds. Hepatology. 2011 Jan;53(1):293-305 Authors: Wang Y, Cui CB, Yamauchi M, Miguez P, Roach M, Malavarca R, Costello MJ, Cardinale V, Wauthier E, Barbier C, Gerber DA, Alvaro D, Reid LM Current protocols for differentiation of stem cells make use of multiple treatments of soluble signals and/or matrix factors and result typically in partial differentiation to mature cells with under- or overexpression of adult tissue-specific genes. We developed a strategy for rapid and efficient differentiation of stem cells using substrata of biomatrix scaffolds, tissue-specific extracts enriched in extracellular matrix, and associated growth factors and cytokines, in combination with a serum-free, hormonally defined medium (HDM) tailored for the adult cell type of interest. Biomatrix scaffolds were prepared by a novel, four-step perfusion decellularization protocol using conditions designed to keep all collagen types insoluble. The scaffolds maintained native histology, patent vasculatures, and ≈1% of the tissue's proteins but >95% of its collagens, most of the tissue's collagen-associated matrix components, and physiological levels of matrix-bound growth factors and cytokines. Collagens increased from almost undetectable levels to >15% of the scaffold's proteins with the remainder including laminins, fibronectins, elastin, nidogen/entactin, proteoglycans, and matrix-bound cytokines and growth factors in patterns that correlate with histology. Human hepatic stem cells (hHpSCs), seeded onto liver biomatrix scaffolds and in an HDM tailored for adult liver cells, lost stem cell markers and differentiated to mature, functional parenchymal cells in ≈1 week, remaining viable and with stable mature cell phenotypes for more than 8 weeks. CONCLUSION: Biomatrix scaffolds can be used for biological and pharmaceutical studies of lineage-restricted stem cells, for maintenance of mature cells, and, in the future, for implantable, vascularized engineered tissues or organs. PMID: 21254177 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Graft Materials and Bone Marrow Stromal Cells in Bone Tissue Engineering. J Biomater Appl. 2011 Mar 1; Authors: Foschi F, Conserva E, Pera P, Canciani B, Cancedda R, Mastrogiacomo M Bone augmentation procedures rely on osteogenic/osteoconductive properties of bone graft material (BGM). A further improvement is represented by use of autologous bone marrow stromal cells (BMSC), expanded in vitro and seeded on BGM before implantation in the bone defect. The effect of different BGMs on BMSC osteogenic differentiation was evaluated. BMSC were cultured in vitro in the presence of different BGM (natural, synthetic, and mixed origins). Cellular morphology was analyzed with scanning electron microscopy. The capability of BMSC to differentiate was determined in vitro by alkaline phosphatase gene expression and enzyme activity at different time points (7, 14, and 28 days) and in vivo by ectopic bone formation of implanted tissue constructs in an immunodeficient murine model. BGM supports the cell adhesion and osteogenic differentiation of BMSC developing a useful tool in the bone tissue engineering. PMID: 21363873 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A novel bioreactor to simulate urinary bladder mechanical properties and compliance for bladder functional tissue engineering. Chin Med J (Engl). 2011 Feb;124(4):568-73 Authors: Wei X, Li DB, Xu F, Wang Y, Zhu YC, Li H, Wang KJ Bioreactors are pivotal tools for generating mechanical stimulation in functional tissue engineering study. This study aimed to create a bioreactor that can simulate urinary bladder mechanical properties, and to investigate the effects of a mechanically stimulated culture on urothelial cells and bladder smooth muscle cells. PMID: 21362283 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Role of Indian hedgehog signaling in palatal osteogenesis. Plast Reconstr Surg. 2011 Mar;127(3):1182-90 Authors: Levi B, James AW, Nelson ER, Brugmann SA, Sorkin M, Manu A, Longaker MT : Cleft lip-cleft palate is a common congenital disability and represents a large biomedical burden. Through the use of animal models, the molecular underpinnings of cleft palate are becoming increasingly clear. Indian hedgehog (Ihh) has been shown to be associated with craniofacial development and to be active in the palatine bone. The authors hypothesize that Indian hedgehog activity plays a role in osteogenesis within the secondary palate and that defects in this pathway may inhibit osteogenesis of the secondary palate. PMID: 21364421 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Coherent anti-Stokes Raman scattering microscopy of human smooth muscle cells in bioengineered tissue scaffolds. J Biomed Opt. 2011 January/February;16(2):021115 Authors: Brackmann C, Esguerra M, Olausson D, Delbro D, Krettek A, Gatenholm P, Enejder A The integration of living, human smooth muscle cells in biosynthesized cellulose scaffolds was monitored by nonlinear microscopy toward contractile artificial blood vessels. Combined coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy was applied for studies of the cell interaction with the biopolymer network. CARS microscopy probing CH(2)-groups at 2845 cm(-1) permitted three-dimensional imaging of the cells with high contrast for lipid-rich intracellular structures. SHG microscopy visualized the fibers of the cellulose scaffold, together with a small signal obtained from the cytoplasmic myosin of the muscle cells. From the overlay images we conclude a close interaction between cells and cellulose fibers. We followed the cell migration into the three-dimensional structure, illustrating that while the cells submerge into the scaffold they extrude filopodia on top of the surface. A comparison between compact and porous scaffolds reveals a migration depth of <10 μm for the former, whereas the porous type shows cells further submerged into the cellulose. Thus, the scaffold architecture determines the degree of cell integration. We conclude that the unique ability of nonlinear microscopy to visualize the three-dimensional composition of living, soft matter makes it an ideal instrument within tissue engineering. PMID: 21361678 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Establishment of a continuous untransfected human corneal endothelial cell line and its biocompatibility to denuded amniotic membrane. Mol Vis. 2011;17:469-80 Authors: Fan T, Zhao J, Ma X, Xu X, Zhao W, Xu B To establish an untransfected human corneal endothelial (HCE) cell line and characterize its biocompatibility to denuded amniotic membrane (dAM). PMID: 21365020 [PubMed - in process] | | | | | | | | | |  | |  | |  |
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