|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | CONNEXIN43 CONNEXON TO GAP JUNCTION TRANSITION IS REGULATED BY ZONULA OCCLUDENS-1. Mol Biol Cell. 2011 Mar 16; Authors: Rhett JM, Jourdan J, Gourdie RG Connexin43 (Cx43) is a gap junction (GJ) protein widely expressed in mammalian tissues that mediates cell-to-cell coupling. Intercellular-channels comprising GJ aggregates form from docking of paired connexons; one each contributed by apposing cells. ZO-1 binds the carboxyl-terminus of Cx43 and we have previously shown that inhibition of Cx43/ZO-1 interaction increases GJ size over 48hrs. Here, we demonstrated that increases in GJ aggregation occur within 2hrs (∼Cx43 half-life) following disruption of Cx43/ZO-1. Immunoprecipitation and Duolink protein-protein interaction assays indicated that inhibition targets ZO-1 binding with Cx43 in GJs, as well as connexons in an adjacent domain that we term the "Perinexus". Consistent with GJ size increases being matched by decreases in connexons, inhibition of Cx43/ZO-1: reduced the extent of perinexal interaction, increased the proportion of connexons docked in GJs relative to undocked connexons in the plasma membrane, and increased GJ intercellular communication while concomitantly decreasing connexon-mediated membrane-permeance in contacting, but not non-contacting cells. ZO-1 siRNA and overexpression experiments verified that loss- and gain-of-ZO-1-function governs the transition of connexons into GJs. It is concluded that ZO-1 regulates the rate of undocked connexon aggregation into GJs, enabling dynamic partitioning of Cx43 channel function between junctional and proximal non-junctional domains of plasma membrane. PMID: 21411628 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | C*07:185, a novel HLA-C*07 allele identified by sequence-based typing. Tissue Antigens. 2011 Mar 17; Authors: Jakubauskas A, Juskevicius D, Griskevicius L A novel allele HLA-C*07:185 differs from HLA-C*07:02 by a single nucleotide substitution that results in a missense mutation Ala 140 Pro (GCT to CCT) encoded in exon 3. PMID: 21410657 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of senescence in mesenchymal stem cells isolated from equine bone marrow, adipose tissue and umbilical cord tissue. Stem Cells Dev. 2011 Mar 16; Authors: Vidal M, Walker NJ, Napoli E, Borjesson DL Mesenchymal stem cells (MSCs) from adult and neonatal tissues are intensively investigated for their use in regenerative medicine. The purpose of this study was to compare the onset of replicative senescence in MSCs isolated from equine bone marrow (BMSC), adipose tissue (ASC) and umbilical cord tissue (UCMSC). MSC proliferation (cell doubling), senescence associated β-galactosidase staining, telomere length, Sox-2 and lineage-specific marker expression were assessed for MSCs harvested from tissues of 4 different donors. The results show that before senescence ensued, all cell types proliferated at approximately 1 day/cell doubling. BMSCs significantly increased population doubling rate by passage 10 and ceased proliferation after a little more than 30 total population doublings while UCMSCs and ASCs achieved about 60 to 80 total population doublings. UCMSC and ASCs showed marked β- galactosidase staining after approximately 70 population doublings while BMSCs stained positive by approximately 30 population doublings. The onset of senescence was associated with significant reduction in telomere length averaging 10.2 kbp at passage 3 and 4.5 kbp in senescent cultures. MSCs stained intensively for osteonectin at senescence compared to earlier passages, while vimentin and low levels of smooth muscle actin were consistently expressed. Sox-2 gene expression was consistently noted in all three MSC types. In conclusion, equine BMSCs appear to senesce much earlier than ASCs and UCMSCs. These results demonstrate the limited passage numbers of subcultured BMSCs available for use in research and tissue engineering and suggest that adipose tissue and umbilical cord tissue may be preferable for tissue banking purposes. PMID: 21410356 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Contagious Itch in Humans. A Study of Visual "Transmission" of Itch in Atopic Dermatitis and Healthy Subjects. Br J Dermatol. 2011 Mar 17; Authors: Papoiu AD, Wang H, Coghill RC, Chan YH, Yosipovitch G Anecdotal evidence suggests "contagious" itch occurs in daily life when we see other people itch and scratch. This phenomenon has not been systematically studied previously, and factors which can amplify itch perception were unknown. We investigated whether exposure to visual cues of itch can induce or intensify itch in healthy and atopic dermatitis subjects. Participants received histamine or a saline control delivered to the forearm and were asked to watch short video clips of people scratching. Spontaneous scratching induced by visual cues was monitored and analyzed. Atopic dermatitis patients reported a higher itch intensity and scratched more frequently while watching itch videos, even in the presence of mock itch stimuli. Human susceptibility to develop itch when exposed to visual cues is confirmed and it appears amplified in atopic dermatitis sufferers. These findings suggest that interpersonal social cues can dramatically alter the subjective sensory experience of itch. PMID: 21410682 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | In Situ Gelable Interpenetrating Double Network Hydrogel Formulated from Binary Components: Thiolated Chitosan and Oxidized Dextran. Biomacromolecules. 2011 Mar 16; Authors: Zhang H, Qadeer A, Chen W In situ gelable interpenetrating double-network hydrogels composed of thiolated chitosan (Chitosan-NAC) and oxidized dextran (Odex), completely devoid of potentially cytotoxic small molecule cross-linkers and that do not require complex maneuvers or catalysis, have been formulated. The interpenetrating network structure is created by Schiff base formations and disulfide bond inter-cross-linkings through exploiting the disparity of their reaction times. Compared with the autogelable thiolated chitosan hydrogels that typically require a relatively long time span for gelation to occur, the Odex/Chitosan-NAC composition solidifies rapidly and forms a well-developed 3D network in a short time span. Compared with typical hydrogels derived from natural materials, the Odex/Chitosan-NAC hydrogels are mechanically strong and resist degradation. The cytotoxicity potential of the hydrogels was determined by an in vitro viability assay using fibroblast as a model cell, and the results reveal that the hydrogels are noncytotoxic. In parallel, in vivo results from subdermal implantation in mice models demonstrate that this hydrogel is not only highly resistant to degradation but also induces very mild tissue response. PMID: 21410248 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Non-coding RNA networks underlying cognitive disorders across the lifespan. Trends Mol Med. 2011 Mar 14; Authors: Qureshi IA, Mehler MF Non-coding RNAs (ncRNAs) and their associated regulatory networks are increasingly being implicated in mediating a complex repertoire of neurobiological functions. Cognitive and behavioral processes are proving to be no exception. In this review, we discuss the emergence of many novel, diverse and rapidly expanding classes and subclasses of short and long ncRNAs. We briefly review the life cycles and molecular functions of these ncRNAs. We also examine how ncRNA circuitry mediates brain development, plasticity, stress responses and aging, and highlight its potential roles in the pathophysiology of cognitive disorders, including neural developmental and age-associated neurodegenerative diseases, as well as those that manifest throughout the lifespan. PMID: 21411369 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | State of the art and future perspectives of articular cartilage regeneration: a focus on adipose-derived stem cells and platelet-derived products. J Tissue Eng Regen Med. 2011 Apr;5(4):e36-51 Authors: Hildner F, Albrecht C, Gabriel C, Redl H, van Griensven M Trauma, malposition and age-related degeneration of articular cartilage often result in severe lesions that do not heal spontaneously. Many efforts over the last centuries have been undertaken to support cartilage healing, with approaches ranging from symptomatic treatment to structural cartilage regeneration. Microfracture and matrix-associated autologous chondrocyte transplantation (MACT) can be regarded as one of the most effective techniques available today to treat traumatic cartilage defects. Research is focused on the development of new biomaterials, which are intended to provide optimized physical and biochemical conditions for cell proliferation and cartilage synthesis. New attempts have also been undertaken to replace chondrocytes with cells that are more easily available and cause less donor site morbidity, e.g. adipose derived stem cells (ASC). The number of in vitro studies on adult stem cells has rapidly increased during the last decade, indicating that many variables have yet to be optimized to direct stem cells towards the desired lineage. The present review gives an overview of the difficulties of cartilage repair and current cartilage repair techniques. Moreover, it reviews new fields of cartilage tissue engineering, including stem cells, co-cultures and platelet-rich plasma (PRP). Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21413156 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Diffusion of dimethyl sulfoxide in tissue engineered collagen scaffolds visualized by computer tomography. Cryo Letters. 2010 Nov-Dec;31(6):493-503 Authors: Bernemann I, Manuchehrabadi N, Spindler R, Choi J, Wolkers WF, Bischof JC, Glasmacher B Cryopreservation is a convenient method for long-term preservation of natural and engineered tissues in regenerative medicine. Homogeneous loading of tissues with CPAs, however, forms one of the major hurdles in tissue cryopreservation. In this study, computer tomography (CT) as a non-invasive imaging method was used to determine the effective diffusion of Me2SO in tissue-engineered collagen scaffolds. The dimensions of the scaffolds were 30 x 30 x 10 mm3 with a homogeneous pore size of 100 microm and a porosity of 98%. CT images were acquired after equilibrating the scaffolds in phosphate buffered saline (PBS) and transferring them directly in 10% (v/v)Me2SO. The Me2SO loading process of the scaffold could thus be measured and visualized in real time. The experimental data were fitted using a diffusion equation. The calculated effective diffusion constant for Me2SO in the PBS loaded scaffold was determined from experimental diffusion studies to be 2.4 x 10(-6) cm2/s at 20 degrees C. PMID: 21410018 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Mechanisms controlling hematopoietic stem cell functions during normal hematopoiesis and hematological malignancies. Wiley Interdiscip Rev Syst Biol Med. 2011 Mar 15; Authors: Warr MR, Pietras EM, Passegué E Hematopoiesis, the process by which all mature blood cells are generated from multipotent hematopoietic stem cells (HSCs), is a finely tuned balancing act in which HSCs must constantly decide between different cell fates: to proliferate, to self-renew or differentiate, to stay quiescent in the bone marrow niche or migrate to the periphery, to live or die. These fates are regulated by a complex interplay between cell-extrinsic cues and cell-intrinsic regulatory pathways whose function is to maintain a homeostatic balance between HSC self-renewal and life-long replenishment of lost blood cells. Improper regulation of these competing cellular programs can transform HSCs and progenitor cells into disease-initiating leukemic stem cells (LSCs). Strikingly, many of the mechanisms required for maintenance of normal HSC fate decisions are equally critical for the aberrant functions of LSCs. Because of the inherent complexities of these molecular mechanisms, a systematic approach to understanding the regulatory networks underlying HSC self-renewal is critical for uncovering the similarities and differences between HSCs and LSCs. In this review, we focus on recent developments in elucidating the regulatory networks governing normal HSC self-renewal programs and their implications for leukemic transformation. We describe the current technical and methodological limitations in isolating and characterizing HSCs and LSCs, and the emerging approaches that may afford a better understanding of the regulation of normal and leukemic hematopoiesis. Finally, we discuss how such basic mechanistic information may be of use for the design of novel therapies that will selectively reprogram and/or eliminate LSCs. WIREs Syst Biol Med 2011 DOI: 10.1002/wsbm.145 For further resources related to this article, please visit the WIREs website. PMID: 21412991 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Endothelial cell behaviour on gas-plasma-treated PLA surfaces: the roles of surface chemistry and roughness. J Tissue Eng Regen Med. 2011 Apr;5(4):301-12 Authors: Shah A, Shah S, Mani G, Wenke J, Agrawal M Glow-discharge gas-plasma (GP) treatment has been shown to induce surface modifications such that cell adhesion and growth are enhanced. However, it is not known which gas used in GP treatment is optimal for endothelial cell function. Polylactic acid (PLA) films treated oxygen, argon, or nitrogen GP were characterized using contact angles, scanning electron microscopy, atomic force microscopy, optical profilometry, and x-ray photoelectron spectroscopy. All three GP treatments decreased the carbon atomic concentration and surface roughness and increased the oxygen atomic concentration. Human umbilical vein endothelial cells were cultured on the PLA films for up to 7 days. Based on proliferation and live/dead assays, surface chemistry was shown to have the greatest effect on the attachment, proliferation, and viability of these cells, while roughness did not have a significant influence. Of the different gases, endothelial cell viability, attachment and proliferation were most significantly increased on PLA surfaces treated with oxygen and argon gas plasma. Copyright © 2010 John Wiley & Sons, Ltd. PMID: 21413158 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Use of cytokine immunotherapy to block CNS demyelination induced by a recombinant HSV-1 expressing IL-2. Gene Ther. 2011 Mar 17; Authors: Zandian M, Mott KR, Allen SJ, Dumitrascu O, Kuo JZ, Ghiasi H We previously have described a model of multiple sclerosis (MS) in which constitutive expression of murine interleukin (IL)-2 by herpes simplex virus type 1 (HSV-1) (HSV-IL-2) causes central nervous system (CNS) demyelination in different strains of mice. In the current study, we investigated whether this HSV-IL-2-induced demyelination can be blocked using recombinant viruses expressing different cytokines or by injection of plasmid DNA. We have found that coinfection of HSV-IL-2-infected mice with recombinant viruses expressing IL-12p35, IL-12p40 or IL-12p35+IL-12p40 did not block the CNS demyelination, and that coinfection with a recombinant virus expressing interferon (IFN)-γ exacerbated it. In contrast, coinfection with a recombinant virus expressing IL-4 reduced demyelination, whereas coinfection of HSV-IL-2-infected mice with a recombinant HSV-1 expressing the IL-12 heterodimer (HSV-IL-12p70) blocked the CNS demyelination in a dose-dependent manner. Similarly, injection of IL-12p70 DNA blocked HSV-IL-2-induced CNS demyelination in a dose-dependent manner and injection of IL-35 DNA significantly reduced CNS demyelination. Injection of mice with IL-12p35 DNA, IL-12p40 DNA, IL-12p35+IL-12p40 DNA or IL-23 DNA did not have any effect on HSV-IL-2-induced demyelination, whereas injection of IL-27 DNA increased the severity of the CNS demyelination in the HSV-IL-2-infected mice. This study demonstrates for the first time that IL-12p70 can block HSV-IL-2-induced CNS demyelination and that IL-35 can also reduce this demyelination, whereas IFN-γ and IL-27 exacerbated the demyelination in the CNS of the HSV-IL-2-infected mice. Our results suggest a potential role for IL-12p70 and IL-35 signaling in the inhibition of HSV-IL-2-induced immunopathology by preventing development of autoaggressive T cells.Gene Therapy advance online publication, 17 March 2011; doi:10.1038/gt.2011.32. PMID: 21412284 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | NOS inhibition synchronizes calcium oscillations in human adipose tissue-derived mesenchymal stem cells by increasing gap-junctional coupling. J Cell Physiol. 2011 Jun;226(6):1642-50 Authors: Sauer H, Sharifpanah F, Hatry M, Steffen P, Bartsch C, Heller R, Padmasekar M, Howaldt HP, Bein G, Wartenberg M Adipose tissue-derived mesenchymal stem cells (ASCs) are a promising stem cell source for cell transplantation. We demonstrate that undifferentiated ASCs display robust oscillations of intracellular calcium [Ca(2+) ](i) which may be associated with stem cell maintenance since oscillations were absent in endothelial cell differentiation medium supplemented with FGF-2. [Ca(2+) ](i) oscillations were dependent on extracellular Ca(2+) and Ca(2+) release from intracellular stores since they were abolished in Ca(2+) -free medium and in the presence of the store-depleting agent thapsigargin. They were inhibited by the phospholipase C antagonist U73,122, the inositol 1,4,5-trisphosphate (InsP(3) ) receptor antagonist 2-aminoethoxydiphenyl borate (2-APB) as well as by the gap-junction uncouplers 1-heptanol and carbenoxolone, indicating regulation by the InsP(3) pathway and dependence on gap-junctional coupling. Cells endogenously generated nitric oxide (NO), expressed NO synthase 1 (NOS 1) and connexin 43 (Cx 43). The nitric oxide NOS inhibitors NG-monomethyl-L-arginine (L-NMMA), N(G)-nitro-L-arginine methyl ester (L-NAME), 2-ethyl-2-thiopseudourea, and diphenylene iodonium as well as si-RNA-mediated down-regulation of NOS 1 synchronized [Ca(2+) ](i) oscillations between individual cells, whereas the NO-donors S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP) as well as the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) were without effects. The synchronization of [Ca(2+) ](i) oscillations was due to an improvement of intracellular coupling since fluorescence recovery after photobleaching (FRAP) revealed increased reflow of fluorescent calcein into the bleached area in the presence of the NOS inhibitors DPI and L-NAME. In summary our data demonstrate that intracellular NO levels regulate synchronization of [Ca(2+) ](i) oscillations in undifferentiated ASCs by controlling gap-junctional coupling. J. Cell. Physiol. 226: 1642-1650, 2011. © 2010 Wiley-Liss, Inc. PMID: 21413022 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | The state of California's modest foray into scientific publishing is drawing attention in a couple of science publications.
Both "The Scientist" and "Nature Medicine" recently carried items dealing with the $600,000 venture by the California stem cell agency in partnership with a North Carolina business, AlphaMed Press of Durham.
Nature published the more fulsome piece that predated action by | | | | | | | | | | | | | | | | | | | | | | | | | Biological approaches toward dental pulp regeneration by tissue engineering. J Tissue Eng Regen Med. 2011 Apr;5(4):e1-e16 Authors: Sun HH, Jin T, Yu Q, Chen FM Root canal therapy has been the predominant approach in endodontic treatment, wherein the entire pulp is cleaned out and replaced with a gutta-percha filling. However, living pulp is critical for the maintenance of tooth homeostasis and essential for tooth longevity. An ideal form of therapy, therefore, might consist of regenerative approaches in which diseased/necrotic pulp tissues are removed and replaced with regenerated pulp tissues to revitalize the teeth. Dental pulp regeneration presents one of the most challenging issues in regenerative dentistry due to the poor intrinsic ability of pulp tissues for self-healing and regrowth. With the advent of modern tissue engineering and the discovery of dental stem cells, biological therapies have paved the way to utilize stem cells, delivered or internally recruited, to generate dental pulp tissues, where growth factors and a series of dentine extracellular matrix molecules are key mediators that regulate the complex cascade of regeneration events to be faithfully fulfilled. Copyright © 2010 John Wiley & Sons, Ltd. PMID: 21413154 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Novel Strategies in Immunosuppression: Issues in Perspective. Transplantation. 2011 Mar 15; Authors: Webber A, Hirose R, Vincenti F Recent findings suggest that a chronic alloimmune response is playing the dominant role in late allograft loss, challenging the notion that most grafts are lost due to the inexorable progression of calcineurin inhibitor (CNI) nephrotoxicity. CNIs have failed to improve long-term outcomes and are associated with multiple metabolic derangements. Thus, improvement in long-term allograft outcomes may depend on new agents with novel mechanisms of action, devoid of the toxicities associated with CNIs. To meet this need, inhibitors of novel pathways in B cell and plasma cell activation have emerged to combat the humoral immune response including belimumab and atacicept, both promising targets of B-cell survival factors and bortezomib and eculizumab, agents currently in trials for desensitization protocols and treatment of antibody-mediated rejection. Promising agents for maintenance immunosuppression, used as monotherapy or synergistically, include monoclonal antibodies and fusion receptor proteins targeting the CD40-CD154 pathway (multiple anti-CD40 antibodies), the CD28-CD80/86 pathway (i.e., belatacept), the LFA3-CD2 pathway (i.e., alefacept), and small molecules such as tofacitinib, a janus kinase 1/3 inhibitor. The induction of allograft tolerance has been attempted with some success with simultaneous bone marrow/kidney transplantation from the same donor, albeit, limited by its associated toxicites. Finally, the exciting fields of tissue engineering and stem cell biology with the repopulation of decellularized organs is ushering in a new paradigm for transplantation. The era of simplified immunosuppression regimens devoid of toxicities is upon us with the promise of dramatic improvement in long term survival. PMID: 21412186 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Type I collagen, fibrin and PuraMatrix matrices provide permissive environments for human endothelial and mesenchymal progenitor cells to form neovascular networks. J Tissue Eng Regen Med. 2011 Apr;5(4):e74-86 Authors: Allen P, Melero-Martin J, Bischoff J The field of tissue engineering seeks to create metabolically demanding, functional tissues, which will require blood vessel networks capable of forming rapidly in a variety of extracellular matrix (ECM) environments. We tested whether human endothelial progenitor cells (EPCs) and mesenchymal progenitor cells (MPCs) could form microvascular networks in type I collagen, fibrin and an engineered peptide hydrogel, PuraMatrix, in 7 days in vivo in immune-deficient mice. These results are compared to those previously published, based on the Matrigel ECM. Perfused blood vessels formed in all three types of ECM within 7 days. Collagen at 5 and 6 mg/ml and 10 mg/ml fibrin supported vessel formation at 30-60 vessels/mm(2) , and PuraMatrix enabled vessel formation to 160 vessels/mm(2) , significantly greater than collagen or fibrin. Vessels were composed of EPCs with perivascular cells on their abluminal surfaces. EPCs injected alone formed a low density of blood vessels in collagen and PuraMatrix, while MPCs injected alone resulted in sparse vessel networks in all ECMs tested. A rheometer was used to determine whether the ECMs which supported vascularization had bulk physical properties similar to or distinct from Matrigel. Collagen and fibrin were the stiffest matrices to support extensive vascularization, with storage moduli in the range 385-510 Pa, while Matrigel, at 80 Pa, and PuraMatrix, at 5 Pa, were far more compliant. Thus, EPCs and MPCs were capable of vasculogenesis in environments having disparate physical properties, although vascular density was greater in more compliant ECMs. We propose that EPC/MPC-mediated vascularization is a versatile technology which may enable the development of engineered organs. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21413157 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of senescence in mesenchymal stem cells isolated from equine bone marrow, adipose tissue and umbilical cord tissue. Stem Cells Dev. 2011 Mar 16; Authors: Vidal M, Walker NJ, Napoli E, Borjesson DL Mesenchymal stem cells (MSCs) from adult and neonatal tissues are intensively investigated for their use in regenerative medicine. The purpose of this study was to compare the onset of replicative senescence in MSCs isolated from equine bone marrow (BMSC), adipose tissue (ASC) and umbilical cord tissue (UCMSC). MSC proliferation (cell doubling), senescence associated β-galactosidase staining, telomere length, Sox-2 and lineage-specific marker expression were assessed for MSCs harvested from tissues of 4 different donors. The results show that before senescence ensued, all cell types proliferated at approximately 1 day/cell doubling. BMSCs significantly increased population doubling rate by passage 10 and ceased proliferation after a little more than 30 total population doublings while UCMSCs and ASCs achieved about 60 to 80 total population doublings. UCMSC and ASCs showed marked β- galactosidase staining after approximately 70 population doublings while BMSCs stained positive by approximately 30 population doublings. The onset of senescence was associated with significant reduction in telomere length averaging 10.2 kbp at passage 3 and 4.5 kbp in senescent cultures. MSCs stained intensively for osteonectin at senescence compared to earlier passages, while vimentin and low levels of smooth muscle actin were consistently expressed. Sox-2 gene expression was consistently noted in all three MSC types. In conclusion, equine BMSCs appear to senesce much earlier than ASCs and UCMSCs. These results demonstrate the limited passage numbers of subcultured BMSCs available for use in research and tissue engineering and suggest that adipose tissue and umbilical cord tissue may be preferable for tissue banking purposes. PMID: 21410356 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Enhanced differentiation of embryonic and neural stem cells to neuronal fates on laminin peptides doped polypyrrole. Macromol Biosci. 2010 Dec 8;10(12):1456-64 Authors: Zhang L, Stauffer WR, Jane EP, Sammak PJ, Cui XT PPy is a conducting polymer material that has been widely investigated for biomedical applications. hESCs and adult rNSCs were grown on four PPy surfaces doped with PSS or peptide from laminin (p20, p31, and a mixture of p20 and p31) respectively. After 7 d, both PPy/p20 and PPy/p31 promoted neuroectoderm formation from hESCs. After 14 d of culture, surfaces containing p20 showed the highest percentage of neuronal differentiation from hESC, while the PPy/p31 surface showed better cell attachment and spreading. In rNSCs cultures, a higher percentage of neurons were found on the PPy/p20 surface than other surfaces at 7 and 14 d. For differentiated neurons, p20 promoted both the primary and total neurite outgrowth. Longer primary neurites were found on p20-containing surfaces and a longer total neurite length was found on PPy/p20 surface. These results demonstrated that, by doping PPy with different bioactive peptides, differentiation of stem cells seeded at different stages of development is affected. PMID: 20954199 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | BMP-12 Treatment of Adult Mesenchymal Stem Cells In Vitro Augments Tendon-Like Tissue Formation and Defect Repair In Vivo. PLoS One. 2011;6(3):e17531 Authors: Lee JY, Zhou Z, Taub PJ, Ramcharan M, Li Y, Akinbiyi T, Maharam ER, Leong DJ, Laudier DM, Ruike T, Torina PJ, Zaidi M, Majeska RJ, Schaffler MB, Flatow EL, Sun HB We characterized the differentiation of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) into tenocyte-like cells in response to bone morphogenetic protein-12 (BMP-12). BM-MSCs were prepared from Sprague-Dawley rats and cultured as monolayers. Recombinant BMP-12 treatment (10 ng/ml) of BM-MSCs for 12 hours in vitro markedly increased expression of the tenocyte lineage markers scleraxis (Scx) and tenomodulin (Tnmd) over 14 days. Treatment with BMP-12 for a further 12-hour period had no additional effect. Colony formation assays revealed that ∼80% of treated cells and their progeny were Scx- and Tnmd-positive. BM-MSCs seeded in collagen scaffolds and similarly treated with a single dose of BMP-12 also expressed high levels of Scx and Tnmd, as well as type I collagen and tenascin-c. Furthermore, when the treated BM-MSC-seeded scaffolds were implanted into surgically created tendon defects in vivo, robust formation of tendon-like tissue was observed after 21 days as evidenced by increased cell number, elongation and alignment along the tensile axis, greater matrix deposition and the elevated expression of tendon markers. These results indicate that brief stimulation with BMP-12 in vitro is sufficient to induce BM-MSC differentiation into tenocytes, and that this phenotype is sustained in vivo. This strategy of pretreating BM-MSCs with BMP-12 prior to in vivo transplantation may be useful in MSC-based tendon reconstruction or tissue engineering. PMID: 21412429 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Application of conductive polymers, scaffolds and electrical stimulation for nerve tissue engineering. J Tissue Eng Regen Med. 2011 Apr;5(4):e17-35 Authors: Ghasemi-Mobarakeh L, Prabhakaran MP, Morshed M, Nasr-Esfahani MH, Baharvand H, Kiani S, Al-Deyab SS, Ramakrishna S Among the numerous attempts to integrate tissue engineering concepts into strategies to repair nearly all parts of the body, neuronal repair stands out. This is partially due to the complexity of the nervous anatomical system, its functioning and the inefficiency of conventional repair approaches, which are based on single components of either biomaterials or cells alone. Electrical stimulation has been shown to enhance the nerve regeneration process and this consequently makes the use of electrically conductive polymers very attractive for the construction of scaffolds for nerve tissue engineering. In this review, by taking into consideration the electrical properties of nerve cells and the effect of electrical stimulation on nerve cells, we discuss the most commonly utilized conductive polymers, polypyrrole (PPy) and polyaniline (PANI), along with their design and modifications, thus making them suitable scaffolds for nerve tissue engineering. Other electrospun, composite, conductive scaffolds, such as PANI/gelatin and PPy/poly(ε-caprolactone), with or without electrical stimulation, are also discussed. Different procedures of electrical stimulation which have been used in tissue engineering, with examples on their specific applications in tissue engineering, are also discussed. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21413155 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | State of the art and future perspectives of articular cartilage regeneration: a focus on adipose-derived stem cells and platelet-derived products. J Tissue Eng Regen Med. 2011 Apr;5(4):e36-51 Authors: Hildner F, Albrecht C, Gabriel C, Redl H, van Griensven M Trauma, malposition and age-related degeneration of articular cartilage often result in severe lesions that do not heal spontaneously. Many efforts over the last centuries have been undertaken to support cartilage healing, with approaches ranging from symptomatic treatment to structural cartilage regeneration. Microfracture and matrix-associated autologous chondrocyte transplantation (MACT) can be regarded as one of the most effective techniques available today to treat traumatic cartilage defects. Research is focused on the development of new biomaterials, which are intended to provide optimized physical and biochemical conditions for cell proliferation and cartilage synthesis. New attempts have also been undertaken to replace chondrocytes with cells that are more easily available and cause less donor site morbidity, e.g. adipose derived stem cells (ASC). The number of in vitro studies on adult stem cells has rapidly increased during the last decade, indicating that many variables have yet to be optimized to direct stem cells towards the desired lineage. The present review gives an overview of the difficulties of cartilage repair and current cartilage repair techniques. Moreover, it reviews new fields of cartilage tissue engineering, including stem cells, co-cultures and platelet-rich plasma (PRP). Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21413156 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Recent progress in the therapeutic applications of nanotechnology. Curr Opin Pediatr. 2011 Apr;23(2):215-20 Authors: Solomon M, D'souza GG The field of pharmaceutical and medical nanotechnology has grown rapidly in recent decades and offers much promise for therapeutic advances. This review is intended to serve as a quick summary of the major areas in the therapeutic application of nanotechnology. PMID: 21412081 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Study on the biological characteristics of adipose stem cells derived from renal adipose capsule cultured in vitro]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2010 Nov;26(11):1078-81 Authors: Wu W, Zheng HG, Zhang DW, Mei YM To investigate the culture conditions and biological characteristics of the adipose-derived stem cells (ADSCs) isolated from renal adipose capsule so as to find a better source of stem cells for the treatment of kidney disease. PMID: 21055345 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Future therapeutical strategies dictated by pre-clinical evidence in ALS. Arch Ital Biol. 2011 Mar;149(1):169-74 Authors: Fornai F, Meininger V, Silani V Classic concepts on amyotrophic lateral sclerosis led to definethe disease as a selective degeneration of upper and lower motor neurons. At present such selectivity is questioned by novel findings. For instance, the occurrence offrontotemporal dementia is now increasingly recognized in the course of ALS. Again, areas outside the central nervous system are targeted in ALS. In keeping with motor areas other cell types surrounding motor neurons such asglia and interneurons are key in the pathogenesis of ALS. This multiple cell involvement may be due to a prion-like diffusion of specific misfolded proteins which are altered in ALS. This is the case of FUS and TDP-43 which harbor a prion domain prone to pathological misfolding. These misfolded proteins are metabolized by the autophagy, but in ALS there is evidence for a specific deficit of autophagy which impedes the clearance of these proteins. These concepts lead to re-analyze the potential therapeutics of ALS. In fact, mere cell substitution (stem cell) therapy appears insufficient to contrast all the alterations in the various pathways affected by ALS. Although preclinical data speed the application of stem cells in human clinical trials, several hurdles limit their translation into new therapies. Future treatments are expected to consider the need to target both motor neurons and neighboring cells which may contribute to the diffusion and persistence of the disease. On this basis the present manuscript describes which future strategies need to be pursued in order to design optimal therapeutic trial in ALS. PMID: 21412723 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Vörner type palmoplantar keratoderma: novel KRT9 mutation associated with knuckle pad-like lesion and recurrent mutation causing digital mutilation. Br J Dermatol. 2011 Mar 17; Authors: Umegaki N, Nakano H, Tamai K, Mitsuhashi Y, Akasaka E, Sawamura D, Katayama I PMID: 21410681 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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