| |  | | | | | WE'RE MAKING IMPROVEMENTS! Feed My Inbox will be undergoing maintenance on Saturday January 8th. No emails will be sent from 8am-11am CST. We appreciate your patience and are so sorry for any inconvenience this may cause. View related blog post for further details. | | | | | | | | | | | | |  | |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Stem cell therapy: a future treatment of stress urinary incontinence. Semin Reprod Med. 2011 Jan;29(1):61-70 Authors: Nikolavasky D, Stangel-Wójcikiewicz K, Stec M, Chancellor MB The main urinary continence mechanism in human is the striated muscle rhabdosphincter that forms a ring around the mid-urethra. Cellular therapy and the use of stem cells transplanted into the site of the rhabdosphincter in a setting of stress urinary incontinence (SUI) may augment sphincter regeneration. Implanted cells may also release trophic factors promoting muscle and nerve integration into this muscle. We review the use of cellular therapy for SUI and our experience with the development of muscle-derived stem cells. PMID: 21207335 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Leukemic T cells are specifically enriched in a unique CD3(dim) CD7(low) subpopulation of CD4(+) T cells in acute-type adult T cell leukemia. Cancer Sci. 2010 Dec 14; Authors: Tian Y, Kobayashi S, Ohno N, Isobe M, Tsuda M, Zaike Y, Watanabe N, Tani K, Tojo A, Uchimaru K The morphological discrimination of leukemic from non-leukemic T cells is often difficult in adult T cell leukemia (ATL) as ATL cells show morphological diversity, with the exception of typical "flower cells." As defects in expression of CD3 as well as CD7 are common in ATL cells, we applied multi-color flow cytometry to detect a putative leukemia-specific cell population in the peripheral blood from ATL patients. CD4(+) CD14(-) cells subjected to two-color analysis based on a CD3 vs. CD7 plot clearly demonstrated the presence of a CD3(dim) CD7(low) subpopulation in each of nine patients with acute-type ATL. The majority of sorted cells from this fraction showed a flower cell-like morphology, and carried a high proviral load for human T cell leukemia virus (HTLV-I). Genomic integration site analysis (inverse long-range PCR) and analysis of the T cell receptor Vβ repertoire by flow cytometry indicated that the majority of leukemia cells were included in the CD3(dim) CD7(low) subpopulation. These results suggest that leukemic T cells are specifically enriched in a unique CD3(dim) CD7(low) subpopulation of CD4(+) T cells in acute-type ATL. PMID: 21205081 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Angiogenesis and osteogenesis enhanced by bFGF ex vivo gene therapy for bone tissue engineering in reconstruction of calvarial defects. J Biomed Mater Res A. 2011 Jan 4; Authors: Qu D, Li J, Li Y, Gao Y, Zuo Y, Hsu Y, Hu J Reconstruction of bone defects by tissue engineered substitutes requires coordinated coupling between osteogenesis and angiogenesis. Basic fibroblast growth factor (bFGF or FGF-2) is a protein which acts actively in osteogenesis and angiogenesis during skeletal healing and development. It is hypothesized that BMSCs transfected with bFGF can directly stimulate regeneration of vascular tissue, and subsequently enhance osseous formation and remodeling after implantation of the tissue engineered bone. This study was designed to examine the impact of bFGF-BMSCs, seeded on nano-hydroxyapatite/polyamide66 (n-HA/PA66) composite scaffold, to enhance angiogenesis and osteogenesis in a calvarial critical-sized defect model in rats. To investigate the vascularization and bone formation of tissue engineered bone, the substrate was removed and processed for immunohistochemical, scanning electron microscopic examinations (SEM), reverse transcriptase-polymerase chain reaction (RT-PCR), dual energy X-ray absorptiometry (DEXA), microvessels counting, and new bone volume assay. The results demonstrate that bFGF mediated ex vivo gene transfer based on BMSCs can accelerate vascularization and bone regeneration on these composite scaffolds. The n-HA/PA66 scaffold combined with the bFGF-BMSCs may mimic the natural process of osteogenesis during repair of defect by tissue engineered bone. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2010. PMID: 21207465 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Influence of polysaccharide composition on the biocompatibility of pullulan/dextran-based hydrogels. J Biomed Mater Res A. 2011 Jan 4; Authors: Abed A, Assoul N, Ba M, Derkaoui SM, Portes P, Louedec L, Flaud P, Bataille I, Letourneur D, Meddahi-Pellé A The implantation of a biomaterial for tissue engineering requires the presence of a suitable scaffold on which the tissue repair and regeneration will take place. Polymers have been frequently used for that purpose because they show similar properties to that of the natural extracellular matrix. Scaffold properties and biocompatibility are modulated by the composition of the polymers used. In this work four polysaccharide-based hydrogels (PSH) made of dextran and pullulan were synthesized. Their in vitro properties were determined and then tested in vivo in a rat model. As pullulan concentration increased in dextran hydrogels, the glass transition temperature and the maximum modulus decreased. In vitro degradation studies for 30 days demonstrated no significant degradation of PSH except for 100% pullulan hydrogel. In vivo tissue response evaluated 30 days after PSH subcutaneous implantation in rats indicated that all PSH were surrounded by a fibrous capsule. Adding pullulan to dextran induced an increased inflammatory reaction compared to PSH-D (100% dextran) or PSH-D(75)P(25) (75% dextran)(.) This in vitro and in vivo data can be used in the design of hydrogels appropriate for tissue engineering applications © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2010. PMID: 21207464 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | PLGA-chitosan/PLGA-alginate nanoparticle blends as biodegradable colloidal gels for seeding human umbilical cord mesenchymal stem cells. J Biomed Mater Res A. 2011 Jan 4; Authors: Wang Q, Jamal S, Detamore MS, Berkland C The natural polymers chitosan and alginate represent an attractive material choice for biodegradable inplants. These were used as coating materials to make positively and negatively charged PLGA nanoparticles, respectively. After blending at total solids concentration >10% wt/vol, these oppositely charged nanoparticles yielded a cohesive colloidal gel. Electrostatic forces between oppositely charged nanoparticles produced a stable 3D porous network that may be extruded or molded to the desired shape. This high concentration colloidal system demonstrated shear-thinning behavior due to the disruption of interparticle interactions. Once the external force was removed, the cohesive property of the colloidal gel was recovered. Scanning electron micrographs of dried colloidal networks revealed an organized, 3D microporous structure. Rheological studies were employed to probe the differences in plasticity and shear sensitivity of colloidal gels. Viability tests of hUCMSCs seeded on the colloidal gels also demonstrated the negligible cytotoxicity of the materials. All the results indicated the potential application of the biodegradable colloidal gels as an injectable scaffold in tissue engineering and drug release. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2010. PMID: 21207461 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bioengineering a vaginal replacement using a small biopsy of autologous tissue. Semin Reprod Med. 2011 Jan;29(1):38-44 Authors: Dorin RP, Atala A, Defilippo RE Many congenital and acquired diseases result in the absence of a normal vagina. Patients with these conditions often require reconstructive surgery to achieve satisfactory cosmesis and physiological function, and a variety of materials have been used as tissue sources. Currently employed graft materials such as collagen scaffolds and small intestine are not ideal in that they fail to mimic the physiology of normal vaginal tissue. Engineering of true vaginal tissue from a small biopsy of autologous vagina should produce a superior graft material for vaginal reconstruction. This review describes our current experience with the engineering of such tissue and its use for vaginal reconstruction in animal models. Our successful construction and implantation of neovaginas through tissue engineering techniques demonstrates the feasibility of similar endeavors in human patients. Additionally, the use of pluripotent stem cells instead of autologous tissue could provide an "off-the-shelf" tissue source for vaginal reconstruction. PMID: 21207333 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Porous alginate/poly(ε-caprolactone) scaffolds: preparation, characterization and in vitro biological activity. Int J Mol Med. 2010 Dec 28; Authors: Grandi C, Di Liddo R, Paganin P, Lora S, Dalzoppo D, Feltrin G, Giraudo C, Tommasini M, Conconi MT, Parnigotto PP In bone tissue engineering, scaffolds with controlled porosity are required to allow cell ingrowth, nutrient diffusion and sufficient formation of vascular networks. The physical properties of synthetic scaffolds are known to be dependent on the biomaterial type and its processing technique. In this study, we demonstrate that the separation phase technique is a useful method to process poly(ε-caprolactone) (PCL) into a desired shape and size. Moreover, using poly(ethylene glycol), sucrose, fructose and Ca2+ alginate as porogen agents, we obtained PCL scaffolds with three-dimensional porous structures characterized by different pore size and geometry. Scanning electron microscopy and porosity analysis indicated that PCL scaffolds prepared with Ca2+ alginate threads resemble the porosity and the homogeneous pore size distribution of native bone. In parallel, MicroCT analysis confirmed the presence of interconnected void spaces suitable to guarantee a biological environment for cellular growth, as demonstrated by a biocompatibility test with MC3T3-E1 murine preosteoblastic cells. In particular, scaffolds prepared with Ca2+ alginate threads increased adhesion and proliferation of MC3T3-E1 cells under basal culture conditions, and upon stimulation with a specific differentiation culture medium they enhanced the early and later differentiated cell functions, including alkaline phosphatase activity and mineralized extracellular matrix production. These results suggest that PCL scaffolds, obtained by separation phase technique and prepared with alginate threads, could be considered as candidates for bone tissue engineering applications, possessing the required physical and biological properties. PMID: 21206967 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Microfabricated platforms for mechanically dynamic cell culture. J Vis Exp. 2010;(46): Authors: Moraes C, Sun Y, Simmons CA The ability to systematically probe in vitro cellular response to combinations of mechanobiological stimuli for tissue engineering, drug discovery or fundamental cell biology studies is limited by current bioreactor technologies, which cannot simultaneously apply a variety of mechanical stimuli to cultured cells. In order to address this issue, we have developed a series of microfabricated platforms designed to screen for the effects of mechanical stimuli in a high-throughput format. In this protocol, we demonstrate the fabrication of a microactuator array of vertically displaced posts on which the technology is based, and further demonstrate how this base technology can be modified to conduct high-throughput mechanically dynamic cell culture in both two-dimensional and three-dimensional culture paradigms. PMID: 21206477 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Dental follicle stem cells and tissue engineering. J Oral Sci. 2010;52(4):541-52 Authors: Honda MJ, Imaizumi M, Tsuchiya S, Morsczeck C Adult stem cells are multipotent and can be induced experimentally to differentiate into various cell lineages. Such cells are therefore a key part of achieving the promise of tissue regeneration. The most studied stem cells are those of the hematopoietic and mesenchymal lineages. Recently, mesenchymal stem cells were demonstrated in dental tissues, including dental pulp, periodontal ligament, and dental follicle. The dental follicle is a loose connective tissue that surrounds the developing tooth. Dental follicle stem cells could therefore be a cell source for mesenchymal stem cells. Indeed, dental follicle is present in impacted teeth, which are commonly extracted and disposed of as medical waste in dental practice. Dental follicle stem cells can be isolated and grown under defined tissue culture conditions, and recent characterization of these stem cells has increased their potential for use in tissue engineering applications, including periodontal and bone regeneration. This review describes current knowledge and recent developments in dental follicle stem cells and their application. (J Oral Sci 52, 541-552, 2010). PMID: 21206155 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Fabrication of a nanofibrous scaffold with improved bioactivity for culture of human dermal fibroblasts for skin regeneration. Biomed Mater. 2011 Jan 5;6(1):015001 Authors: Chandrasekaran AR, Venugopal J, Sundarrajan S, Ramakrishna S Engineering dermal substitutes with electrospun nanofibres have lately been of prime importance for skin tissue regeneration. Simple electrospinning technology served to produce nanofibrous scaffolds morphologically and structurally similar to the extracellular matrix of native tissues. The nanofibrous scaffolds of poly(l-lactic acid)-co-poly(ε-caprolactone) (PLACL) and PLACL/gelatin complexes were fabricated by the electrospinning process. These nanofibres were characterized for fibre morphology, membrane porosity, wettability and chemical properties by FTIR analysis to culture human foreskin fibroblasts for skin tissue engineering. The nanofibre diameter was obtained between 282 and 761 nm for PLACL and PLACL/gelatin scaffolds; expressions of amino and carboxyl groups and porosity up to 87% were obtained for these fibres, while they also exhibited improved hydrophilic properties after plasma treatment. The results showed that fibroblasts proliferation, morphology, CMFDA dye expression and secretion of collagen were significantly increased in plasma-treated PLACL/gelatin scaffolds compared to PLACL nanofibrous scaffolds. The obtained results prove that the plasma-treated PLACL/gelatin nanofibrous scaffold is a potential biocomposite material for skin tissue regeneration. PMID: 21205999 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Fabrication and optimization of alginate hydrogel constructs for use in 3D neural cell culture. Biomed Mater. 2011 Jan 5;6(1):015002 Authors: Frampton JP, Hynd MR, Shuler ML, Shain W Two-dimensional (2D) culture systems provide useful information about many biological processes. However, some applications including tissue engineering, drug transport studies, and analysis of cell growth and dynamics are better studied using three-dimensional (3D) culture systems. 3D culture systems can potentially offer higher degrees of organization and control of cell growth environments, more physiologically relevant diffusion characteristics, and permit the formation of more extensive 3D networks of cell-cell interactions. A 3D culture system has been developed using alginate as a cell scaffold, capable of maintaining the viability and function of a variety of neural cell types. Alginate was functionalized by the covalent attachment of a variety of whole proteins and peptide epitopes selected to provide sites for cell attachment. Alginate constructs were used to entrap a variety of neural cell types including astroglioma cells, astrocytes, microglia and neurons. Neural cells displayed process outgrowth over time in culture. Cell-seeded scaffolds were characterized in terms of their biochemical and biomechanical properties, effects on seeded neural cells, and suitability for use as 3D neural cell culture models. PMID: 21205998 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Biodegradable polycaprolactone-chitosan three-dimensional scaffolds fabricated by melt stretching and multilayer deposition for bone tissue engineering: assessment of the physical properties and cellular response. Biomed Mater. 2011 Jan 5;6(1):015009 Authors: Thuaksuban N, Nuntanaranont T, Pattanachot W, Suttapreyasri S, Cheung LK Fabrication of polycaprolactone (PCL)-chitosan (CS) three-dimensional (3D) scaffolds using the novel technique of melt stretching and multilayer deposition was introduced. In brief, firstly, the PCL-CS monofilaments containing 0% (pure PCL), 10%, 20% and 30% CS by weight were fabricated by melting and stretching processes. Secondly, the desired multilayer (3D) scaffolds were fabricated by arranging and depositing the filaments. Physical properties of the filaments and the scaffolds were evaluated. MC3T3-E1 cell lines were seeded on the scaffolds to assess their proliferation. A typical micro-groove pattern was found on the surfaces of pure PCL filaments due to stretching. The filaments of PCL-30%CS had the highest tendency of fracture during stretching and could not be used to form the scaffold. Increasing CS proportions tended to reduce the micro-groove pattern, surface roughness, tensile strength and elasticity of the filaments, whilst compressive strength of the PCL-CS scaffolds was not affected. The average pore size and porosity of the scaffolds were 536.90 ± 17.91 µm and 45.99 ± 2.8% respectively. Over 60 days, degradation of the scaffolds gradually increased (p > 0.05). The more CS containing scaffolds were found to increase in water uptake, but decrease in degradation rate. During the culture period, the growth of the cells in PCL-CS groups was significantly higher than in the pure PCL group (p < 0.05). On culture-day 21, the growth in the PCL-20%CS group was significantly higher than the other groups (p < 0.05). In conclusion, the PCL-20%CS scaffolds obtained the optimum results in terms of physical properties and cellular response. PMID: 21205996 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Proliferation and chondrogenic differentiation of CD105-positive enriched rat synovium-derived mesenchymal stem cells in three-dimensional porous scaffolds. Biomed Mater. 2011 Jan 5;6(1):015006 Authors: Qi J, Chen A, You H, Li K, Zhang D, Guo F Stem cell-based tissue engineering has provided an alternative strategy to treat cartilage lesions, and synovium-derived mesenchymal stem cells (SMSCs) are considered as a promising cell source for cartilage repair. In this study, the SMSCs were isolated from rat synovium, and CD105-positive (CD105(+)) cells were enriched using magnetic activated cell sorting. Sorted cells were subsequently seeded onto the chitosan-alginate composite three-dimensional (3D) porous scaffolds and cultured in chondrogenic culture medium in the presence of TGF-β(3) and BMP-2 for 2 weeks in vitro. After 2 weeks in culture, scanning electron microscopy results showed that cells attached and proliferated well on scaffolds, and secreted extracellular matrix were also observed. From day 7 to day 14, the total DNA and glucosaminoglycan content of the cells cultured in scaffolds were found to have increased significantly, and cell cycle analyses revealed that the percentage of cells in the S and G2/M phases increased and the percentage of cells in the G0/G1 phase decreased. Compared with non-sorted cells, the sorted cells cultured in scaffolds underwent more chondrogenic differentiation, as evidenced by higher expression of type II collagen and Sox9 at the protein and mRNA levels. The results suggest that CD105(+) enriched SMSCs may be a potential cell source for cartilage tissue engineering, and the chitosan-alginate composite 3D porous scaffold could provide a favorable microenvironment for supporting proliferation and chondrogenic differentiation of cells. PMID: 21205995 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of immunocompatibility of tissue-engineered periosteum. Biomed Mater. 2011 Jan 5;6(1):015005 Authors: Zhao L, Zhao J, Wang S, Xia Y, Liu J, He J, Wang X Tissue-engineered periosteum (TEP) and 'intramembranous ossification' may be an alternative approach to bone tissue engineering. In the previous study we attained successful bone defect reparation with homemade TEP in an allogenic rabbit model. But its allogenic immunocompatibility remained unknown. In this study TEP was constructed by seeding osteogenically induced mesenchymal stem cells of rabbit onto porcine small intestinal submucosa (SIS). A mixed lymphocyte reaction (MLR) was applied to evaluate the in vitro immunogenicity. The ratio of CD4(+)/CD8(+) T-lymphocytes was tested kinetically to evaluate the systematic reaction of the TEP allograft, and a histological examination was performed to investigate local inflammation and ectopic osteogenesis. MLR indicated that TEP had a higher in vitro immunostimulation than SIS (p < 0.05). The ratios of CD4(+)/CD8(+) lymphocytes increased in both TEP and SIS implanted groups in 2 weeks, followed by a decrease to a normal level from 2 to 4 weeks. Histological examination revealed modest lymphocyte infiltration for no more than 2 weeks. Moreover, subcutaneous ectopic ossification was observed in TEP allograft animals (8/12). Our findings imply that TEP has a certain immune reaction for the allograft, but it is not severe enough to impact osteogenesis in the allogenic rabbit model. PMID: 21205993 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cardiomyocyte clusters derived from human embryonic stem cells share similarities with human heart tissue. J Mol Cell Biol. 2010 Oct;2(5):276-83 Authors: Asp J, Steel D, Jonsson M, Améen C, Dahlenborg K, Jeppsson A, Lindahl A, Sartipy P Cardiotoxicity testing is a key activity in the pharmaceutical industry in order to detect detrimental effects of new drugs. A reliable human in vitro model would both be beneficial in selection of lead compounds and be important for reducing animal experimentation. However, the human heart is a complex organ composed of many distinct types of cardiomyocytes, but cardiomyocyte clusters (CMCs) derived from human embryonic stem cells could be an option for a cellular model. Data on functional properties of CMCs demonstrate similarities to their in vivo analogues in human. However, development of an in vitro model requires a more thorough comparison of CMCs to human heart tissue. Therefore, we directly compared individually isolated CMCs to human fetal, neonatal, adult atrial and ventricular heart tissues. Real-time qPCR analysis of mRNA levels and protein staining of ion channels and cardiac markers showed in general a similar expression pattern in CMCs and human heart. Moreover, a significant decrease in beat frequency was noted after addition of Zatebradine, a blocker to I(f) involved in regulation of spontaneous contraction in CMCs. The results underscore the similarities of CMCs to human cardiac tissue, and further support establishment of novel cardiotoxicity assays based on the CMCs in drug discovery. PMID: 20802012 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage. Osteoarthritis Cartilage. 2010 Jul;18(7):1001; author reply 1002 Authors: Longo UG, Forriol F, Maffulli N, Denaro V PMID: 20346405 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | The chairman of the California stem cell ageny, Robert Klein, recently wrote an op-ed piece for the San Jose Business Journal replete with superlatives about the significance of the state's $3 billion research effort.
It represented the type of publicity that the agency will need to convince California voters to approve the roughly $5 billion, new bond issue that Klein is touting.
Klein is a | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine meets gynecology. Semin Reprod Med. 2011 Jan;29(1):3-4 Authors: McGee EA PMID: 21207329 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine: Are calcium phosphate ceramics 'smart' biomaterials? Nat Rev Rheumatol. 2011 Jan;7(1):8-9 Authors: Boyan BD, Schwartz Z PMID: 21206482 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | The Wnt receptor Ryk controls specification of GABAergic neurons versus oligodendrocytes during telencephalon development. Development. 2011 Feb;138(3):409-19 Authors: Zhong J, Kim HT, Lyu J, Yoshikawa K, Nakafuku M, Lu W GABAergic neurons and oligodendrocytes originate from progenitors within the ventral telencephalon. However, the molecular mechanisms that control neuron-glial cell-fate segregation, especially how extrinsic factors regulate cell-fate changes, are poorly understood. We have discovered that the Wnt receptor Ryk promotes GABAergic neuron production while repressing oligodendrocyte formation in the ventral telencephalon. We demonstrate that Ryk controls the cell-fate switch by negatively regulating expression of the intrinsic oligodendrogenic factor Olig2 while inducing expression of the interneuron fate determinant Dlx2. In addition, we demonstrate that Ryk is required for GABAergic neuron induction and oligodendrogenesis inhibition caused by Wnt3a stimulation. Furthermore, we showed that the cleaved intracellular domain of Ryk is sufficient to regulate the cell-fate switch by regulating the expression of intrinsic cell-fate determinants. These results identify Ryk as a multi-functional receptor that is able to transduce extrinsic cues into progenitor cells, promote GABAergic neuron formation, and inhibit oligodendrogenesis during ventral embryonic brain development. PMID: 21205786 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Disrupted plasma membrane localization of equilibrative nucleoside transporter 2 in the chemoresistance to gemcitabine (dFdCyd) of human pancreatic cancer cells. Cancer Sci. 2010 Dec 17; Authors: Nishio R, Tsuchiya H, Yasui T, Matsuura S, Kanki K, Kurimasa A, Hisatome I, Shiota G Although the nucleoside pyrimidine analogue gemcitabine is the most effective single agent in the palliation of advanced pancreatic cancer, cellular resistance to gemcitabine treatment is a major problem in the clinical scene. To clarify the molecular mechanisms responsible for chemoresistance to gemcitabine, mRNA expression of the key enzymes including cytidine deaminase (CDA), deoxycytidine kinase (dCK), 5'-nucleotidase (NT5), equilibrative nucleoside transporter 1 and 2 (ENT1 and ENT2), dCMP deaminase (dCMPK), ribonucleotide reductase M1 and M2 (RRM1 and RRM2), thymidylate synthase (TS) and CTP synthase (CTPS) was examined. The interacellular uptake of gemcitabine was greatly impaired in the chemoresistant cell lines due to dysfunction of ENT1 and ENT2. Protein expression of ENT 1 and ENT2 and their protein coding sequences were not altered. Immunohistochemical and western blot analyses revealed that localization of ENT2 on the plasma membrane was disrupted. These data suggest that the disrupted localization of ENT2 is one of causes of the impaired uptake of gemcitabine, resulting in the gain of chemoresistance to gemcitabine. PMID: 21205085 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Immune maintenance of self in morphostasis of distinct tissues, tumor growth, and regenerative medicine. Scand J Immunol. 2010 Nov 20; Authors: Bukovsky A Morphostasis (tissue homeostasis) is a complex process consisting of three circumstances: (1) tissue renewal from stem cells, (2) preservation of tissue cells in a proper differentiated state, and (3) maintenance of tissue quantity. This can be executed by a tissue control system (TCS) consisting of vascular pericytes, immune system-related components - monocyte-derived cells (MDC), T cells, and immunoglobulins, and autonomic innervation. Morphostasis is established epigenetically, during the critical developmental period corresponding to the morphogenetic immune adaptation. Subsequently, the tissues are maintained in a state of differentiation reached during the adaptation by a "stop effect" of MDC influencing markers of differentiating tissue cells and presenting self antigens to T cells. Retardation or acceleration of certain tissue differentiation during adaptation results in its persistent functional immaturity or premature aging. The tissues being absent during adaptation, like ovarian corpus luteum, are handled as a "graft." Morphostasis is altered with age advancement, due to the degenerative changes of the immune system. That is why the aging of individuals and increased incidence of neoplasia and degenerative diseases occur. Hybridization of tumor stem cells with normal tissue cells causes an augmentation of neoplasia by host pericytes and MDC stimulating a "regeneration" of depleted functional cells. Degenerative diseases are associated with apoptosis. If we are able to change morphostasis in particular tissue, we may disrupt apoptotic process of the cell. An ability to manage the "stop effect" of MDC may provide treatment for early postnatal tissue disorders, improve regenerative medicine, and delay physical, mental, and hormonal aging. PMID: 21204896 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effects of donor age, gender and in vitro cellular aging on the phenotype, functional and molecular characteristics of mouse Bone Marrow-derived Mesenchymal Stem Cells. Stem Cells Dev. 2011 Jan 4; Authors: Katsara O, Mahaira LG, Iliopoulou EG, Moustaki A, Antsaklis A, Loutradis D, Stefanidis K, Baxevanis CN, Papamichail M, Perez SA Mesenchymal Stem Cells (MSCs) are a very important adult stem cell population with a multitude of potential applications in regenerative medicine. The thorough characterization of the bone marrow MSC (BM-MSC) population derived from the BALB/c species was essential considering the significance of the murine model amongst animal models. In the present study, we examined the effect of gender, age and in vitro culture on the basic properties (proliferation, differentiation and immunosuppressive potential) of BM-MSCs. We found a decline in the progenitor frequencies from the BM of adult mice, lower MSC frequencies in all female donors and an increase in the BM-MSC proliferation rate upon in vitro propagation. We also examined BM-MSCs for the expression of the three major ESC transcription factors: Oct3/4, Sox-2 and Nanog as well as two mRNA binding proteins: Crd-bp/Imp1 and Dazl which are expressed in primitive stem cells, UCB- HSC and amniotic fluid stem cells, respectively. Furthermore, it has been reported that these two genes are critical for embryonic development. In this study, therefore, we report, for the first time, the expression of Crd-bp/Imp1 and Dazl in BM-MSCs. Dazl, Oct3/4 and Sox2 were detected in relatively low levels in contrast to Crd-bp/Imp1, its major target, c-Myc, as well as Nanog that were expressed redundantly, irrespective of sex, donor age or in vitro passaging. These findings could further support the extrinsic theory of aging of the MSC population and the potential implication of embryonic genes in adult stem cell physiology. PMID: 21204633 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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