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