|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Single-walled carbon nanotubes alter Schwann cell behavior differentially within 2D and 3D environments. J Biomed Mater Res A. 2010 Oct 14; Authors: Behan BL, Dewitt DG, Bogdanowicz DR, Koppes AN, Bale SS, Thompson DM Both spinal cord injury (SCI) and large-gap peripheral nerve defects can be debilitating affecting a patient's long-term quality of life and presently, there is no suitable treatment for functional regeneration of these injured tissues. A number of works have suggested the benefits of electrical stimulation to promote both glial migration and neuronal extension. In this work, an electrically conductive hydrogel containing single-walled carbon nanotubes (SWCNT) for neural engineering applications is presented and the Schwann cell (SC) response to SWCNT is examined in both 2D and 3D microenvironments. Results from clonogenic and alamarBlue(®) assays in 2D indicate that SWCNT (10-50 μg mL(-1)) inhibit SC proliferation but do not affect cell viability. Following SWCNT exposure in 2D, changes in SC morphology can be observed with the nanomaterial attached to the cell membrane at concentrations as low as 10 μg mL(-1). In contrast to the results gathered in 2D, SC embedded within the 3D hydrogel loaded with 10-50 μg mL(-1) of SWCNT exhibited little or no measurable change in cell proliferation, viability, or morphology as assessed using a digestion assay, alamarBlue, and confocal microscopy. Collectively, this highlights that an electrically-conductive SWCNT collagen I-Matrigel™ biomaterial may be suitable for neural tissue engineering and is able to sustain populations of SC. Findings suggest that 2D nanoparticle toxicity assays may not be accurate predictors of the 3D response, further motivating the examination of these materials in a more physiologically relevant environment. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2010. PMID: 20949573 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Paramagnetic nanofibrous composite films enhance the osteogenic responses of pre-osteoblast cells. Nanoscale. 2010 Oct 15; Authors: Meng J, Zhang Y, Qi X, Kong H, Wang C, Xu Z, Xie S, Gu N, Xu H In this work, a paramagnetic nanofibrous composite film was fabricated with poly lactide, hydroxyapatite and γ-Fe(2)0(3) nanoparticles using the electrospinning technique. The composite film significantly enhanced the proliferation, differentiation and ECM secretion of the osteoblast cells under a static magnetic field, which offers promising application potentials in bone tissue engineering and bone regeneration therapy. PMID: 20949222 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Chitosan composites for bone tissue engineering-an overview. Mar Drugs. 2010;8(8):2252-66 Authors: Venkatesan J, Kim SK Bone contains considerable amounts of minerals and proteins. Hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2)] is one of the most stable forms of calcium phosphate and it occurs in bones as major component (60 to 65%), along with other materials including collagen, chondroitin sulfate, keratin sulfate and lipids. In recent years, significant progress has been made in organ transplantation, surgical reconstruction and the use of artificial protheses to treat the loss or failure of an organ or bone tissue. Chitosan has played a major role in bone tissue engineering over the last two decades, being a natural polymer obtained from chitin, which forms a major component of crustacean exoskeleton. In recent years, considerable attention has been given to chitosan composite materials and their applications in the field of bone tissue engineering due to its minimal foreign body reactions, an intrinsic antibacterial nature, biocompatibility, biodegradability, and the ability to be molded into various geometries and forms such as porous structures, suitable for cell ingrowth and osteoconduction. The composite of chitosan including hydroxyapatite is very popular because of the biodegradability and biocompatibility in nature. Recently, grafted chitosan natural polymer with carbon nanotubes has been incorporated to increase the mechanical strength of these composites. Chitosan composites are thus emerging as potential materials for artificial bone and bone regeneration in tissue engineering. Herein, the preparation, mechanical properties, chemical interactions and in vitro activity of chitosan composites for bone tissue engineering will be discussed. PMID: 20948907 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Advances in cord blood transplants in adults. F1000 Med Rep. 2010;2: Authors: Doan PL, Chao NJ Umbilical cord blood is an acceptable source of hematopoietic stem cells for patients with malignant diseases but has limitations in its use. In this review, we will discuss these limitations and the recent advances in cord blood transplants that may enable cord blood to become more widely available as an alternative stem cell source for adults for the treatment of malignant diseases and for use in regenerative medicine. PMID: 20948874 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Reconstructing blood from induced pluripotent stem cells. F1000 Med Rep. 2010;2: Authors: Papapetrou EP, Sadelain M The direct reprogramming of human somatic cells to induced pluripotent stem cells (iPSCs) offers exciting prospects for disease modelling and regenerative medicine. Several recent reports support the feasibility of generating various blood cell types from iPSCs through in vitro-directed differentiation. However, the derivation of hematopoietic stem cells (HSCs) capable of long-term reconstitution of all hematopoietic lineages appears to be more challenging. These hurdles notwithstanding, cell engineering strategies aiming to correct genetic defects at the stem cell level are already emerging. Robust methodologies for the generation of definitive human HSCs conferring high-level, multilineage, long-term, hematopoietic reconstitution thus are direly needed before the therapeutic potential and safety of iPSC-derived cell products can be thoroughly investigated. PMID: 20948840 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | p53: Guardian of reprogramming. Cell Cycle. 2010 Oct 9;9(19) Authors: Menendez S, Camus S, 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 indepth 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 - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Delivery of rosiglitazone from an injectable triple interpenetrating network hydrogel composed of naturally derived materials. Biomaterials. 2010 Oct 12; Authors: Zhang H, Qadeer A, Mynarcik D, Chen W An in situ gelable and biodegradable triple-interpenetrating network (3XN) hydrogel, completely devoid of potentially cytotoxic extraneous small molecule crosslinkers, is formulated from partially oxidized dextran (Odex), teleostean and N-carboxyethyl chitosan (CEC). Both the rheological profile and mechanical strength of the 3XN hydrogel approximate the combined characteristics of the three individual hydrogels composed of the binary partial formulations (i.e., Odex/CEC, Odex/teleostean, and CEC/teleostean). The 3XN hydrogel is considerably more resistant to fibroblast-mediated degradation compared to each partial formulation in cell culture models; this is attributable to the interpenetrating triple-network structure. The presence of teleostean in the 3XN hydrogel imparts cell affinity, constituting an environment amenable to fibroblast growth. in vivo subdermal injection into mouse model shows that the 3XN hydrogel does not induce extensive inflammatory response nor is there any evidence of tissue necrosis, further confirming the non-cytotoxicity of the hydrogel and its degradation byproducts. Importantly, the capability of the 3XN hydrogel to serve as a sustained drug delivery vehicle is confirmed using rosiglitazone as a model drug. The presence of rosiglitazone profoundly changes the cell/tissue interactions with the subdermally injected 3XN hydrogel. Rosiglitazone suppresses both the inflammatory response and tissue repair in a dose-dependent manner and considerably moderated the hydrogel degradation. PMID: 20947157 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Association between prostaglandin E receptor 3 polymorphisms and Stevens-Johnson syndrome identified by means of a genome-wide association study. J Allergy Clin Immunol. 2010 Oct 12; Authors: Ueta M, Sotozono C, Nakano M, Taniguchi T, Yagi T, Tokuda Y, Fuwa M, Inatomi T, Yokoi N, Tashiro K, Kinoshita S BACKGROUND: Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucosa. They often affect the ocular surface and can result in permanent visual dysfunction. OBJECTIVES: We sought to discover genetic markers for SJS/TEN susceptibility. METHODS: We performed a genome-wide association study with 60 patients and 300 control subjects. We applied stringent filter and visual assessments for selecting single nucleotide polymorphisms (SNPs) and a high false discovery rate threshold. We fine-mapped the region where a candidate SNP was found and confirmed the results by means of sequencing. We evaluated the function of agonist-activated prostaglandin E receptor 3 (EP3), the gene for which contained several SNPs, in regulating cytokine production in human conjunctival epithelial (CE) cells. The expression levels of EP3 in the CE cells from patients and control subjects were also compared. RESULTS: We identified 3 SNPs that passed the false discovery rate threshold. One (rs17131450) was close to the EP3 gene. Therefore we analyzed the EP3 region in detail and identified 5 other SNPs. We confirmed the association between SJS/TEN and all 6 SNPs. Activated EP3 was expressed in control CE cells, and it suppressed polyI:C-stimulated cytokine production, suggesting that EP3 might help prevent ocular surface inflammation. Concordantly, the EP3 levels were much lower in the CE cells of the patients than in those of the control subjects. CONCLUSION: We demonstrated, using both genetic and functional analyses, that EP3 could be a key player in the pathogenesis of SJS/TEN accompanied by ocular complications. PMID: 20947153 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The Myc Connection: ES Cells and Cancer. Cell. 2010 Oct 15;143(2):184-6 Authors: Rothenberg ME, Clarke MF, Diehn M Gene profiling experiments have revealed similarities between cancer and embryonic stem (ES) cells. Kim et al. (2010) dissect the gene expression signature of ES cells into three functional modules and find that the Myc module, including genes targeted by Myc-interacting proteins, accounts for most of the similarity between ES and cancer cells. PMID: 20946977 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Neural stem cells differentiation ability of human umbilical cord mesenchymal stromal cells is not altered by cryopreservation. Neurosci Lett. 2010 Oct 11; Authors: Zhang HT, Chen H, Zhao H, Dai YW, Xu RX Human umbilical mesenchymal stem cells (HUMSCs) have potential therapeutic use in the recovery of central nervous system injury for their ability to differentiate into neural stem cells. However, for transformed HUMSCs to be constantly available for use during surgery a reliable method of cell storage is necessary. The present study aimed to determine whether a simple method of cryopreservation by slow cooling with Me(2)SO had an effect on the proliferation, secretion and differentiation capacities of HUMSCs. These results demonstrate that cryopreservation has no effect on the phenotype, cell cycle, cell proliferation and the ability to secret neurotrophins. Non-cropreserved and cryopreserved HUMSCs showed the similar ability to differentiate into neural stem-like cells. There results shows that cryopreservation by slow cooling with Me(2)SO is effective to retain the proliferation and neural differentiation ability of HUMSCs, cryopreserved HUMSCs maybe very useful for future clinical applications in neural regenerative medicine. PMID: 20946937 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effect of collagen I and fibronectin on the adhesion, elasticity and cytoskeletal organization of prostate cancer cells. Biochem Biophys Res Commun. 2010 Oct 11; Authors: Docheva D, Padula D, Schieker M, Clausen-Schaumann H Despite of intensive research efforts, the precise mechanism of prostate cancer metastasis in bone is still not fully understood. Several studies have suggested that specific matrix production by the bone cells, such as collagen I, supports cancer cell invasion. The aim of this study was to investigate the effect of collagen I (COL1) and fibronectin (FN) on cell adhesion, cell elasticity and cytoskeletal organization of prostate cancer cells. Two cell lines, bone marrow- (PC3) and lymph node-derived (LNCaP) were cultivated on COL1 and FN (control protein). By using a quantitative adhesion assay and time-lapse analysis, it was found that PC3, but not LNCaP, adhered strongly and were more spread on COL1. Next, PC3 and LNCaP were evaluated by atomic force microscopy (AFM) and flatness shape factor and cellular Young's modulus were calculated. The shape analysis revealed that PC3 were significantly flatter when grown on COL1 in comparison to LNCaP. In general, PC3 were also significantly stiffer than LNCaP and furthermore, their stiffness increased upon interaction with COL1. Since cell stiffness is strongly dependent on actin organization, phalloidin-based actin staining was performed and revealed that, of the two cell types as well as the two different matrix proteins, only PC3 grown on COL1 formed robust actin cytoskeleton. In conclusion, our study showed that PC3 cells have a strong affinity towards COL1. On this matrix protein, the cells adhered strongly and underwent a specific cell flattening. Moreover, with the establishment of PC3 contact to COL1 a significant increase of PC3 stiffness was observed due to a profound cytoskelatal rearrangement. PMID: 20946884 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Three-dimensional in vitro follicle growth: overview of culture models, biomaterials, design parameters and future directions. Reprod Biol Endocrinol. 2010 Oct 14;8(1):119 Authors: Desai N, Alex A, Abdelhafez F, Calabro A, Goldfarb J, Fleischman A, Falcone T ABSTRACT: In vitro ovarian follicle culture is a new frontier in assisted reproductive technology with tremendous potential, especially for fertility preservation. Folliculogenesis within the ovary is a complex process requiring interaction between somatic cell components and the oocyte. Conventional two-dimensional culture on tissue culture substrata impedes spherical growth and preservation of the spatial arrangements between oocyte and surrounding granulosa cells. Granulosa cell attachment and migration can leave the oocyte naked and unable to complete the maturation process. Recognition of the importance of spatial arrangements between cells has spurred research in to three-dimensional culture system. Such systems may be vital when dealing with human primordial follicles that may require as long as three months in culture. In the present work we review pertinent aspects of in vitro follicle maturation, with an emphasis on tissue-engineering solutions for maintaining the follicular unit during the culture interval. We focus primarily on presenting the various 3-dimensional culture systems that have been applied for in vitro maturation of follicle:oocyte complexes. We also try to present an overview of outcomes with various biomaterials and animal models and also the limitations of the existing systems. PMID: 20946661 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cardiac Cell Therapies: The Next Generation. Cardiovasc Ther. 2010 Oct 14; Authors: Choi YH, Saric T, Nasseri B, Hühn S, Van Linthout S, Hetzer R, Tschöpe C, Stamm C Although significant advances have been made in terms of pharmacological, catheter-based, and surgical palliation, heart failure remains a fatal disease. As a curative concept, regenerative medicine aims at the restoration of the physiologic cellular composition of diseased organs. So far, clinical cardiac regeneration attempts have only been moderately successful, but a better understanding of myocardial cell homeostasis and somatic as well as embryonic stem cell biology has opened the door for the development of more potent therapeutic cardiac regeneration strategies. Accumulating evidence indicates that the postnatal mammalian heart retains a pool of tissue-specific progenitor cells and is also repopulated by cells from extracardiac sources. However, this intrinsic myocardial regeneration potential clearly needs to be augmented by either manipulation of the cell cycle of differentiated cells, activation of resident cardiac progenitor cells, and/or the transplantation of exogenous cells. This review summarizes the recent developments in cardiac regenerative medicine, many of which may find their way into the clinical setting in the foreseeable future. PMID: 20946322 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Possibility of Skin Epithelial Cell Transdifferentiation in Tracheal Reconstruction. Artif Organs. 2010 Oct 14; Authors: Kim JH, Kong WH, Kim JG, Kim HJ, Seo SW In tissue engineering, injured tissue is normally reconstructed with cells obtained from that tissue itself. However, it is difficult to obtain cells for reconstruction of the trachea because of its shape and limited accessibility. Therefore, other cell sources having similar form and function or stem cells are used for tracheal reconstruction. In a previous study, we used autologous skin epithelial cells and successfully reconstructed canine tracheas. We found that the tracheal epithelial layer was completely covered with ciliated cells, which is a remarkable finding because skin and tracheal epithelial cells originate from different germinal layers and have very different forms. In this study, to elucidate the origin of the ciliated cells, we identified the stem cell contents of skin epithelial cells on primary culture, marked the skin epithelial cells with PKH26 dye, and transplanted them onto canine tracheas. After 5 months, we identified PKH26 fluorescence on the tracheal epithelial layers, especially over the tracheal cartilages. Consequently, we demonstrated that transplanted autologous skin epithelial stem cells can remain viable on the trachea for a few months and can transdifferentiate into tracheal epithelial cells and chondrocytes. PMID: 20946312 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Explant Culture: An Efficient Method to Isolate Adipose-Derived Stromal Cells for Tissue Engineering. Artif Organs. 2010 Oct 14; Authors: Jing W, Xiao J, Xiong Z, Yang X, Huang Y, Zhou M, Chen S, Lin Y, Tian W Enzymatic digestion, the commonly used method of adipose-derived stromal cells isolation, is time consuming and expensive, especially when applied to large volumes of tissue. In the present study, the characteristics of the cells obtained by adipose tissue explant culture were studied. We found that adipose tissue fragments could adhere onto the growth surface of flasks in a very short time after plating and that fibroblast-like cells migrated from the explants and reached confluence. Morphologic analysis and surface markers expression suggested the mesenchymal origin of the cells derived from adipose tissue explants. After in vitro expansion these cells were successfully induced into adipogenic, osteogenic, and chondrogenic lineages, which demonstrated their multipotency. The high growth rate and colony-forming efficiency of explant-derived cells were similar to those of cells obtained by digestion. Furthermore, explant culture gave higher yield of cells than digestion method after primary culture. The experiment of ectopic adipogenesis in nude mice suggested the prospects for tissue engineering of these cells. In conclusion, we obtained multipotent stromal cells from adipose tissue by explant culture, and this method was simple, time saving, and gave a high yield of cells. Therefore, explant culture can be used as an effective way to isolate adipose-derived stromal cells for tissue engineering. PMID: 20946305 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Molecular weight fibrinogen variants alter gene expression and functional characteristics of human endothelial cells. J Thromb Haemost. 2010 Oct 5; Authors: Weijers EM, Van Wijhe MH, Joosten L, Horrevoets AJ, De Maat MP, Van Hinsbergh VW, Koolwijk P Background: Fibrin is a temporary matrix, which not only seals a wound, but also provides a temporary matrix structure for invading cells during wound healing. Two naturally occurring fibrinogen variants, high molecular weight (HMW) and low molecular weight (LMW) fibrinogen, display different properties in supporting angiogenesis in vivo and in vitro. Objectives: This study aims to investigate the functional characteristics and molecular mechanisms of human microvascular endothelial cells (HMVEC) cultured on HMW- and LMW-fibrin matrices. Methods and Results: HMVEC on HMW-fibrin matrices showed increased proliferation and tube formation as compared to their counterparts on unfractionated- and LMW-fibrin. Degradation of HMW-fibrin was markedly enhanced by the presence of HMVEC, that of LMW-fibrin only slightly. However, the expression of fibrinolysis regulating proteins and integrins were similar. Subsequent micro-array analysis revealed that the expression of 377 genes differed significantly between HMVEC cultured on HMW- and LMW-fibrin. Among these genes UNC5B, DLL4 and DLL4-Notch downstream targets Hey1, Hey2 and Hes1 were increased in HMVEC on LMW-fibrin. However, pharmacological and genetic (DLL4 siRNA) inhibition DLL4-Notch signaling blunted rather than enhanced proliferation and tube formation by HMVEC on both fibrin variants. Conclusions: Heterogeneity in natural occurring fibrinogen strongly influences endothelial cell proliferation and tube formation and causes alterations in gene expressions, including that of DLL4-Notch. The higher fibrinolytic sensitivity of HMW-fibrin in the presence of HMVEC contributes to increased tube formation. While DLL4-Notch was altered, it did not explain the enhanced tube formation in HMW-fibrin. This study provides new perspectives for biological and tissue engineering applications. PMID: 20946180 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Generation of mesenchymal stem cell from human umbilical cord tissue using combination of enzymatic and mechanical disassociation method. Cell Biol Int. 2010 Oct 15; Authors: Tong CK, Vellasamy S, Tan BC, Abdullah M, Vidyadaran S, Seow HF, Ramasamy R Mesenchymal Stem Cells (MSC) promise a great potential for regenerative medicine due to their unique properties of self-renewal, high plasticity, modulation of immune response and the flexibility for genetic modification. Therefore, the increasing demand for cellular therapy necessitates a larger scale production of MSC however; the technical and ethical issues had put a halt on it. To date, studies have shown that MSC could be derived from human umbilical cord (UC) which is once considered as clinical waste. In this study, we have compared the two conventional methods which are classic enzymatic digestion and explant method with our newly tailored enzymatic-mechanical disassociation method to generate UC-MSC. The generated UC-MSC from the methods above were characterised based on their immunophenotyping, early embryonic transcription factors expression and mesodermal differentiation ability. Our results show that enzymatic-mechanical disassociation method increase the initial nucleated cell yield greatly (approximately 160-fold) and maximised the successful rate of UC-MSC generation. Enzymatic-mechanical disassociation derived UC-MSC exhibited fibroblastic morphology and surface markers expression of CD105, CD73, CD29, CD90 and MHC Class I. Furthermore, these cells constitutively express early embryonic transcription factors (Nanog, Oct-4, Sox-2, and Rex-1), as confirmed by RT-PCR, indicating their multi potency and high self-renewal capacity. They are also capable of differentiate into osteoblasts and adipocytes when given an appropriate induction. The present study demonstrates a new and efficient approach in generating MSC from UC, hence serve as ideal alternative source of mesenchymal stem cell for clinical and research use. PMID: 20946106 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Myogenic differentiation of mesenchymal stem cells co-cultured with primary myoblasts. Cell Biol Int. 2010 Oct 15; Authors: Beier JP, Bitto FF, Lange C, Klumpp D, Arkudas A, Bleiziffer O, Boos A, Horch RE, Kneser U Background Tissue Engineering of skeletal muscle is a promising method to reconstruct loss of muscle tissue. The aim of this study was to evaluate mesenchymal stem cells as new cell source for this application. Results As a new approach to differentiate the mesenchymal stem cells (MSC) towards the myogenic lineage, co-cultivation with primary myoblasts was developed in this study and myogenic potential of green fluorescenting protein (GFP)-transduced rat MSC co-cultured with primary rat myoblasts was assessed. Myogenic potential of MSC was analysed by immunocytochemistry, fluorescence activated cell sorting and quantitative polymerase chain reaction. MSC - myoblast fusion phenomena leading to hybrid myotubes were evaluated using a novel method to evaluate myotube fusion ratios based on phase contrast and fluorescence microscopy. Furthermore, MSC constitutively expressed the myogenic markers myogenic enhancer factor 2 (MEF2) and a-sarcomeric actin and MEF2 expression was upregulated upon co-cultivation with primary myoblasts and the addition of myogenic medium supplements. Significantly higher numbers of MSC nuclei were involved in myotube formations when basic fibroblast growth factor (bFGF) and dexamethasone were added to co-cultures. Conclusion In summary we developed and determined optimal co-culture conditions for MSC myogenic differentiation up to myotube formations as a promising step towards applicability of MSC as a cell source for skeletal muscle Tissue Engineering as well as other muscle-cell based therapies. PMID: 20946104 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Integrative emphases on intimate, intrinsic propensity/pathological processes--causes of self recovery limits and also, subtle related targets for neuroprotectionl pleiotropicity/multimodal actions, by accessible therapeutic approaches--in spinal cord injuries. J Med Life. 2010 Jul-Sep;3(3):262-74 Authors: Onose G, Haras M, Anghelescu A, Mureşanu D, Giuglea C, Daia Chendreanu C BACKGROUND: The last two decades have come up with some important progresses in the genetic, immune, histochemical and bio (nano)-technological domains, that have provided new insight into cellular/molecular mechanisms, occurring in the central nervous system (CNS)--including in spinal cord-injuries. METHODS: In previous works, emerging from our theoretical and practical endeavors in the field, we have thoroughly described the principal intimate propensity and the pathophysiological processes--representing intrinsic limitations for self-recovery after SCI, and, at the same time, subtle targets for neuroprotection/recovery--and reviewed the main related worldwide-published reports. The aim of this paper is to emphasize the connections between such main aspects and some feasible integrative solutions, including the ones for clinical practice. RESULTS: Consequently, we stress upon some therapeutic suggestions regarding this subject matter by systematizing the most up to date and efficient ones--obviously, within major limits, according to the very low capacities of CNS/ spinal cord (SC) to post-injury self preserve and recover. Moreover, we also talk about accessible drugs, respectively those being already in clinical use (but at present, mainly used to treat other conditions, including the neurological ones) and hence, with relatively well known, determined effects and/or respectively, restrictions. DISCUSSIONS: The recent advances in the knowledge on the basic components of the afore mentioned CNS/ SC propensity for self destroying and inefficient endogenous repair mechanisms in the actual new context, will hopefully be, from now on, more effectively correlated with revolutionary--mostly still experimental--treatments, especially by using stem cells within tissue engineering, including, if needed, more advanced/courageous approaches, based on somatic cell nuclear transfer (SCNT). CONCLUSIONS: This paper contains the scientific motivated highlighting of some already available drugs, "neuroprotective" (and not only) properties too, which enable practitioners with (although not yet capable to cure--but anyway) more efficient therapeutic means, to approach the extremely difficult and still painfully disappointing domain, of spinal cord injury (SCI). PMID: 20945817 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Bone marrow stromal cells as an inducer for cardiomyocyte differentiation from mouse embryonic stem cells. Ann Anat. 2010 Sep 20;192(5):314-21 Authors: Yue F, Johkura K, Tomotsune D, Shirasawa S, Yokoyama T, Nagai M, Sasaki K Bone marrow stromal cells (BMSCs) secrete soluble factors and display varied cell-biological functions. To confirm the ability and efficiency of BMSCs to induce embryonic stem cells (ESCs) into cardiomyocytes, mouse embryoid bodies (EBs) were co-cultured with rat BMSCs. After about 10 days, areas of rhythmically contracting cells in more solid aggregates became evident with bundle-like structures formed along borders between EB outgrowth and BMSC layer. ESC-derived cardiomyocytes exhibited sarcomeric striations when stained with troponin I (Trop I), organized in separated bundles. Besides, the staining for connexin 43 was detected in cell-cell junctions, which demonstrated that ESC-derived cardiomyocytes were coupled by gap junction in culture. The related genes of cardiomyocytes were found in these beating and no-beating EBs co-cultured with BMSCs. In addition, an improved efficiency of cardiomyocyte differentiation from ESC-BMSC co-culture was found in the serum-free medium: 5-fold up-regulation in the number of beating area compared with the serum medium. Effective cardiac differentiation was also recognized in transfer filter assay and in condition medium obtained from BMSC culture. A clear increase in the expression of cardiac genes and TropI protein confirmed further cardiac differentiation by BMP4 and Retinoic Acid (RA) treatment. These results demonstrate that BMSCs can induce cardiomyocyte differentiation from ESCs through soluble factors and enhance it with BMP4 or RA treatment. Serum-free ESC-BMSC co-culture represents a defined in vitro model for identifying the cardiomyocyte-inducing activity from BMSCs and, in addition, a straightforward experimental system for assessing clinical applications. PMID: 20801009 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Rapid repair and regeneration of damaged rabbit sciatic nerves by tissue-engineered scaffold made from nano-silver and collagen type I. Injury. 2010 May;41(5):522-7 Authors: Ding T, Luo ZJ, Zheng Y, Hu XY, Ye ZX A tissue-engineered scaffold with nano-silver and collagen type I was constructed and investigated for its ability to adsorb laminin and the usefulness in the repair and regeneration of damaged peripheral nerves in animals. The nano-silver scaffold displayed ideal microtubule structure under electronic microscope; even distribution of the nano-silver particles was also seen with energy spectrometry. After immersion in a laminin solution, the laminin-attached scaffolds were implanted into rabbits to repair a 10-mm injury of the sciatic nerve. At 30 days post-implantation, regeneration of the damaged nerve was evaluated by transmission electron microscopy, electrophysiological examination and fluoro-gold (FG) retrograde labelling. Compared with the control collagen-scaffold without nano-silver, the nano-silver-containing scaffold showed a higher rate of laminin adsorption, regenerated a nerve with a thicker myelin sheath and improved the nerve conduction velocity and nerve potential amplitude. FG retrograde labelled the newly grown axons in the spinal cord cortex anterior horn and the dorsal root ganglion. These results demonstrate the superior functionality of the nano-silver-collagen scaffold in the adsorption to laminin and subsequent regeneration of damaged peripheral nerves. PMID: 19524233 [PubMed - indexed for MEDLINE] | | | | | | | | | |  | |  | |  |
No comments:
Post a Comment