|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | Prospective separation of normal and leukemic stem cells based on differential expression of TIM3, a human acute myeloid leukemia stem cell marker. Proc Natl Acad Sci U S A. 2011 Mar 7; Authors: Jan M, Chao MP, Cha AC, Alizadeh AA, Gentles AJ, Weissman IL, Majeti R Hematopoietic tissues in acute myeloid leukemia (AML) patients contain both leukemia stem cells (LSC) and residual normal hematopoietic stem cells (HSC). The ability to prospectively separate residual HSC from LSC would enable important scientific and clinical investigation including the possibility of purged autologous hematopoietic cell transplants. We report here the identification of TIM3 as an AML stem cell surface marker more highly expressed on multiple specimens of AML LSC than on normal bone marrow HSC. TIM3 expression was detected in all cytogenetic subgroups of AML, but was significantly higher in AML-associated with core binding factor translocations or mutations in CEBPA. By assessing engraftment in NOD/SCID/IL2Rγ-null mice, we determined that HSC function resides predominantly in the TIM3-negative fraction of normal bone marrow, whereas LSC function from multiple AML specimens resides predominantly in the TIM3-positive compartment. Significantly, differential TIM3 expression enabled the prospective separation of HSC from LSC in the majority of AML specimens with detectable residual HSC function. PMID: 21383193 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Placenta perfusion has hematopoietic and mesenchymal progenitor stem cell potential. Transfusion. 2011 Mar 7; Authors: Tsagias N, Koliakos I, Lappa M, Karagiannis V, Koliakos GG BACKGROUND: Placenta is a valuable source of stem cells for cell therapy and future application in the field of regenerative medicine. This is due to the plasticity and the immunomodulatory effects of the stem cells that it contains. In this study we present a totally closed method for hematopoietic and nonhematopoietic stem cell isolation from human term placenta. STUDY DESIGN AND METHODS: Sixty-eight placenta units were collected and manipulated for the residual fetal blood drainage. After delivery, placenta flushing with citrate-phosphate-dextrose-adenine was evaluated. RESULTS: Placenta flushing using a totally closed system led to a significant amount of hematopoietic progenitor cells and multipotent mesenchymal stem cells (MSCs) without additional microbial risk, free of maternal cell contamination. CONCLUSION: Traditionally discarded after childbirth, the term placenta now appears to be an easily accessible and abundant source of diverse origin stem cells suitable for banking strategies and for future clinical applications, including adult therapy. PMID: 21382046 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A 3D model of ovarian cancer cell lines on peptide nanofiber scaffold to explore the cell-scaffold interaction and chemotherapeutic resistance of anticancer drugs. Int J Nanomedicine. 2011;6:303-10 Authors: Yang Z, Zhao X RADA16-I peptide hydrogel, a type of nanofiber scaffold derived from self-assembling peptide RADA16-I, has been extensively applied to regenerative medicine and tissue repair in order to develop novel nanomedicine systems. In this study, using RADA16-I peptide hydrogel, a three-dimensional (3D) cell culture model was fabricated for in vitro culture of three ovarian cancer cell lines. Firstly, the peptide nanofiber scaffold was evaluated by transmission electron microscopy and atom force microscopy. Using phase contrast microscopy, the appearance of the representative ovarian cancer cells encapsulated in RADA16-I peptide hydrogel on days 1, 3, and 7 in 24-well Petri dishes was illustrated. The cancer cell-nanofiber scaffold construct was cultured for 5 days, and the ovarian cancer cells had actively proliferative potential. The precultured ovarian cancer cells exhibited nearly similar adhesion properties and invasion potentials in vitro between RADA16-I peptide nanofiber and type I collagen, which suggested that RADA16-I peptide hydrogel had some similar characteristics to type I collagen. The precultured ovarian cancer cells had two-fold to five-fold higher anticancer drug resistance than the conventional two-dimensional Petri dish culture. So the 3D cell model on peptide nanofiber scaffold is an optimal type of cell pattern for anticancer drug screening and tumor biology. PMID: 21383855 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Regeneration and repair of peripheral nerves with different biomaterials: review. Microsurgery. 2010 Oct;30(7):574-88 Authors: Siemionow M, Bozkurt M, Zor F Peripheral nerve injury may cause gaps between the nerve stumps. Axonal proliferation in nerve conduits is limited to 10-15 mm. Most of the supportive research has been done on rat or mouse models which are different from humans. Herein we review autografts and biomaterials which are commonly used for nerve gap repair and their respective outcomes. Nerve autografting has been the first choice for repairing peripheral nerve gaps. However, it has been demonstrated experimentally that tissue engineered tubes can also permit lead to effective nerve repair over gaps longer than 4 cm repair that was previously thought to be restorable by means of nerve graft only. All of the discoveries in the nerve armamentarium are making their way into the clinic, where they are, showing great potential for improving both the extent and rate of functional recovery compared with alternative nerve guides. PMID: 20878689 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Micro-RNA response to imatinib mesylate in patients with chronic myeloid leukemia. Haematologica. 2010 Aug;95(8):1325-33 Authors: Flamant S, Ritchie W, Guilhot J, Holst J, Bonnet ML, Chomel JC, Guilhot F, Turhan AG, Rasko JE Micro-RNAs (miRNAs) control gene expression by destabilizing targeted transcripts and inhibiting their translation. Aberrant expression of miRNAs has been described in many human cancers, including chronic myeloid leukemia. Current first-line therapy for newly diagnosed chronic myeloid leukemia is imatinib mesylate, which typically produces a rapid hematologic response. However the effect of imatinib on miRNA expression in vivo has not been thoroughly examined. PMID: 20460641 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | A novel model for diffusion based release kinetics using an inverse numerical method. Med Eng Phys. 2011 Mar 5; Authors: Mohammadi H, Herzog W We developed and analyzed an inverse numerical model based on Fick's second law on the dynamics of drug release. In contrast to previous models which required two state descriptions of diffusion for long- and short-term release processes, our model is valid for the entire release process. The proposed model may be used for identifying and reducing experimental errors associated with measurements of diffusion based release kinetics. Knowing the initial and boundary conditions, and assuming Fick's second law to be appropriate, we use the methods of Lagrange multiplier along with least-square algorithms to define a cost function which is discretized using finite difference methods and is optimized so as to minimize errors. Our model can describe diffusion based release kinetics for static and dynamic conditions as accurately as finite element methods, but results are obtained in a fraction of CPU time. Our method can be widely used for drug release procedures and for tissue engineering/repair applications where oxygenation of cells residing within a matrix is important. PMID: 21382735 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Designed hybrid scaffolds consisting of polycaprolactone microstrands and electrospun collagen-nanofibers for bone tissue regeneration. J Biomed Mater Res B Appl Biomater. 2011 Mar 7; Authors: Lee H, Yeo M, Ahn S, Kang DO, Jang CH, Lee H, Park GM, Kim GH Biomedical scaffolds used in bone tissue engineering should have various properties including appropriate bioactivity, mechanical strength, and morphologically optimized pore structures. Collagen has been well known as a good biomaterial for various types of tissue regeneration, but its usage has been limited due to its low mechanical property and rapid degradation. In this work, a new hybrid scaffold consisting of polycaprolactone (PCL) and collagen is proposed for bone tissue regeneration. The PCL enhances the mechanical properties of the hybrid scaffold and controls the pore structure. Layered collagen nanofibers were used to enhance the initial cell attachment and proliferation. The results showed that the hybrid scaffold yielded better mechanical properties of pure PCL scaffold as well as enhanced biological activity than the pure PCL scaffold did. The effect of pore size on bone regeneration was investigated using two hybrid scaffolds with pore sizes of 200 ± 20 and 300 ± 27 μm. After post-seeding for 7 days, the cell proliferation with pore size, 200 ± 20 μm, was greater than that with pore size, 300 ± 27 μm, due to the high surface area of the scaffold. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011. PMID: 21384546 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Loss of mitochondrial complex I activity potentiates dopamine neuron death induced by microtubule dysfunction in a Parkinson's disease model. J Cell Biol. 2011 Mar 7;192(5):873-82 Authors: Choi WS, Palmiter RD, Xia Z Mitochondrial complex I dysfunction is regarded as underlying dopamine neuron death in Parkinson's disease models. However, inactivation of the Ndufs4 gene, which compromises complex I activity, does not affect the survival of dopamine neurons in culture or in the substantia nigra pars compacta of 5-wk-old mice. Treatment with piericidin A, a complex I inhibitor, does not induce selective dopamine neuron death in either Ndufs4(+/+) or Ndufs4(-/-) mesencephalic cultures. In contrast, rotenone, another complex I inhibitor, causes selective toxicity to dopamine neurons, and Ndufs4 inactivation potentiates this toxicity. We identify microtubule depolymerization and the accumulation of cytosolic dopamine and reactive oxygen species as alternative mechanisms underlying rotenone-induced dopamine neuron death. Enhanced rotenone toxicity to dopamine neurons from Ndufs4 knockout mice may involve enhanced dopamine synthesis caused by the accumulation of nicotinamide adenine dinucleotide reduced. Our results suggest that the combination of disrupting microtubule dynamics and inhibiting complex I, either by mutations or exposure to toxicants, may be a risk factor for Parkinson's disease. PMID: 21383081 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Bottom-Up Signaling from HGF-Containing Surfaces Promotes Hepatic Differentiation of Mesenchymal Stem Cells. Biochem Biophys Res Commun. 2011 Mar 4; Authors: Ghaedi M, Tuleuova N, Zern MA, Wu J, Revzin A The capacity of stem cells to differentiate into specific cell types makes them very promising in tissue regeneration and repair.However, realizing this promise requires novel methods for guiding lineage-specific differentiation of stem cells.In this study, hepatocyte growth factor (HGF), an important morphogeninliver development, was co-printed with collagen I (Col) to create arrays of protein spots on glass. Human adipose stem cells (ASCs) were cultured on top of the HGF/Col spots for 2 weeks. The effects of surface-immobilized HGF on hepatic differentiation of ASCs were analyzed using RT-PCR, ELISA and immunocytochemistry. Stimulation of stem cells with HGF from the bottom-up caused an upregulation in synthesis of α-fetoprotein and albumin, as determined by immunocytochemistry and ELISA. RT-PCR results showed that the mRNA levels for albumin, α-fetoprotein and α1antitrypsin were 10 to 20 fold higher in stem cells cultured on the HGF/Col arrays compared to stem cells on Col only spots. Our results show that surfaces containing HGF co-printed with ECM proteinsmay be used to differentiate mesenchymal stem cells such as ASCs into hepatocyte-like cells. These results underscore the utility of growth factor-containing culture surfaces for stem cell differentiation. PMID: 21382341 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bioactive Plasma-Polymerized Bipolar Films for Enhanced Endothelial Cell Mobility. Macromol Biosci. 2011 Mar 7; Authors: Yang Z, Tu Q, Wang J, Lei X, He T, Sun H, Huang N A facile approach to a highly bio-active interface material is reported. XPS reveals that polar entities exist at the interface between PPAam and PPAac nanolayers. They induce strong dipolar orientation polarizability and cause the redistribution of charges, which results in a remarkable increase of polar surface energy and hydrophilicity of the multistack bipolar films. In particular bipolar films with amine groups on their outermost surface show strongly enhanced cellular mobility. The attachment, adhesion, proliferation, migration, and coverage of ECs are significantly enhanced on such films. They are therefore promising as vascular implant materials, and could have applications as coating materials for tissue engineering. PMID: 21384555 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The role of extracellular conditions during CaCo-2 cells growth: a preliminary study for numerical model validation. Eur Rev Med Pharmacol Sci. 2011 Jan;15(1):61-70 Authors: Ledda M, De Lazzari C, Lisi A, Fresiello L, Grimaldi S, Piccioni MG, Di Matteo A, Fusco L, Lanzi L, Caldarera CM, Alessandri N One important limitation in cell therapy protocols, and regenerative medicine (an innovative and promising strategy for different pathologies treatment), is the lack of knowledge about cells engraftment, proliferation and differentiation. In order to allow an efficient and successful cell transplant, it is necessary to predict the logistics, economic and timing issues during cellular injection. It has been reported that several parameters, such as cells number, temperature and extracellular pH (pH0) value can influence metabolic pathways and cellular growth. Numerical analysis and model can help to reduce and understand the effects of the above environmental conditions on cell survival. The aim of this paper is to develop the first step of cells transplantation in order to identify "in vitro", which parameters can be useful to develop and validate a numerical model, able to evaluate "in vivo" cells engraftment and proliferation. PMID: 21381500 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | All the Embryo's a Stage, and Olig2 in Its Time Plays Many Parts. Neuron. 2011 Mar 10;69(5):833-5 Authors: Gaber ZB, Novitch BG Olig2 is essential for the selection of motor neuron and oligodendrocyte fates and the choice of neural progenitors to either proliferate or differentiate. Three new studies demonstrate that these diverse actions of Olig2 are gated by phosphorylation at two distinct motifs and that Olig2's proliferative function acts in opposition to the p53 tumor suppressor pathway. PMID: 21382543 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Analysis of cell characterization using cell surface markers in the dermis. J Dermatol Sci. 2011 Feb 15; Authors: Hasebe Y, Hasegawa S, Hashimoto N, Toyoda M, Matsumoto K, Umezawa A, Yagami A, Matsunaga K, Mizutani H, Nakata S, Akamatsu H BACKGROUND: In recent years, it has been reported that stem cells exist in the mesenchymal tissues of the bone marrow and adipose. These stem cells are thought to express specific cell surface markers such as CD44, CD54, CD105, CD90, and CD271 and have been confirmed to be pluripotent. Furthermore, although it has been reported that stem cells are also present in the dermis, their cell surface markers and characteristics are not fully understood. OBJECTIVE: To confirm the presence of stem cells in the dermis and their ability, employing the mesenchymal stem cell markers which have previously been reported as an indication. METHODS: We analyzed the percentages of CD44 (+), CD54 (+), CD90 (+), CD105 (+), and CD271 (+) cells in the dermis of neonatal mice (HR-1 mouse) by performing immunostaining and FACS. Secondly, we isolated each type of marker-positive and -negative cells from dermal tissues and evaluated their proliferation potential and their ability to differentiate into adipocytes, osteoblasts, and chondrocytes. RESULTS: According to the immunostaining and FACS results, we confirmed that stem cells that express CD44, CD54, CD90, CD105, and CD271 are present in the dermal tissues of neonatal mice. In addition, when we measured the proliferation and differentiation potentials of each type of marker-positive cells, it was revealed that cells expressing CD54 or CD271 have a high proliferation potential and are able to differentiate into adipocytes, osteoblasts, and chondrocytes. CONCLUSIONS: These results indicated that dermal tissues contain stem cells that express CD44, CD54, CD90, CD105, and CD271 which are stem cell markers. More precisely, it was suggested that both CD54 (+) and CD271 (+) stem cells have high proliferation and differentiation potentials. PMID: 21382697 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Hippocampus development and function: role of epigenetic factors and implications for cognitive disease. Clin Genet. 2010 Oct;78(4):321-33 Authors: Lagali PS, Corcoran CP, Picketts DJ The hippocampus is a primary region of the brain controlling the formation of memories and learned behaviours. The ability to learn or form a memory requires a neuron to translate a transient signal into gene expression changes that have a long-lasting effect on synapse activity and connectivity. Numerous studies over the past decade have detailed changes in epigenetic modifications under various learning paradigms to support a role for chromatin remodelling in these processes. Moreover, the identification of mutations in epigenetic regulators as the cause of mental retardation or intellectual disability (MR/ID) disorders further strengthens their importance to learning and memory. Animal models for many of these disorders are emerging and advancing our understanding of the molecular mechanisms linking epigenetic regulation and cognitive function. Here, we review how chromatin remodelling proteins implicated in MR/ID contribute to the development of the hippocampus and memory formation. PMID: 20681996 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Comparative Cell Behavior on Carbon Coated TiO(2) Nanotube Surfaces for Osteoblasts vs. Osteo-progenitor Cells. Acta Biomater. 2011 Mar 4; Authors: Brammer KS, Choi C, Frandsen CJ, Oh S, Johnston G, Jin S Surface engineering approaches that alter the topological chemistry of a substrate could be used as an effective tool for directing cell interactions and their subsequent function. It is well known that the physical environment of nanotopography has positive effects on cell behavior, yet direct comparisons of nanotopographic surface chemistry has not been fully explored. Here within we compare TiO(2) nanotubes vs. carbon coated TiO(2) nanotubes for probing osteogenic cell behaviors, including osteoblast (bone cells) and mesenchymal stem cell (MSC) (osteo-progenitor cells) interaction with the different surface chemistries (TiO(2) vs. carbon). The roles played by the material surface chemistry of the nanotubes did not have an effect on the adhesion, growth or morphology, but had major influence on the alkaline phosphatase (ALP) activity of osteoblast cells, where the original TiO(2) chemistry had superior ALP levels. In addition, the chemistry effect caused different levels of the osteogenic differentiation in MSCs; however, it was the carbon coated TiO(2) nanotubes having the greater advantage with higher levels of osteo-differentiation. It was observed in this study that (a) chemistry plays a role in cell functionality, such as ALP activity and osteogenic protein gene expression (PCR), and (b) different cell types may have different chemical preferences for optimal function. The ability to optimize cell behavior, using surface chemistry factors, has a profound effect on both orthopedic and tissue engineering in general. This study aims to highlight the importance of the chemistry of the material carrier in osteogenic tissue engineering schemes. PMID: 21382531 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The usefulness of the collagen and elastin sponge derived from salmon as an artificial dermis and scaffold for tissue engineerin. Biomed Res. 2011;32(1):29-36 Authors: Matsumoto Y, Ikeda K, Yamaya Y, Yamashita K, Saito T, Hoshino Y, Koga T, Enari H, Suto S, Yotsuyanagi T Collagen sponge is one of the medical materials that are frequently used in clinical medicine. However, the problem of prion disease harmfully affected the usage of mammals-derived medical materials. Since there have been no reports about prion disease occurring in marine products, we produced the collagen and elastin sponge (CES) made from salmon, and investigated whether the CES could be a substitute for mammalian collagen sponge. Fibroblasts were seeded in the CES to examine whether the CES could be used as a scaffold for tissue engineering. The results of the WST-1 assay showed that the fibroblasts were viable and were well proliferated in the CES. To examine whether the CES could be used as an artificial dermis, the CES and TERUDERMIS (traditional collagen sponge) were grafted onto the skin defects on the dorsum of rats. The histological findings of these ulcers showed non-significant difference between the CES and TERUDERMIS. Because of the safety, the abundance of the resources, and the possessing same ability as TERUDERMIS, the biomedical materials derived from marine products may be a substitute for those derived from mammals. PMID: 21383508 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Strategies to manage permanent non-vital teeth with open apices: a clinical update. Int Dent J. 2011 Feb;61(1):25-30 Authors: Mohammadi Z If dental pulp injury occurs prior to complete root formation and apical closure, normal root development is halted. This condition produces several complications. Firstly, the apical diameter of the canal is often larger than the coronal diameter, so debridement is difficult. Secondly, the lack of an apical stop makes the obturation in all dimensions virtually impossible. And finally, the thin walls of the root canal are prone to fracture, so that surgical treatment is generally not a viable option. There are a number protocols to manage non-vital open-apex teeth such as apexification, apical barrier technique (one-visit apexification), orthograde root filling using MTA, triple antibiotic paste, and tissue engineering concept. The aim of this paper is to review these treatment protocols. PMID: 21382030 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |  | |  | |  |
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