|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | |  | |  | |  |
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