|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | The Nicaraguan anchorage where the California Stem Cell
Report was based the last few weeks. Hopalong is the
name of our craft and home.
The California Stem Cell Report will be on a break for a week or two while we make a passage from Nicaragua past Costa Rica to Panama. We will resume postings when we again find an Internet connection. | | | | | | | | | | | | | | | | | | | | | | | | California Gov. Jerry Brown and three other top state officials are balking at making nominations as early as next month for the new chair of the $3 billion California stem cell agency.
In a letter to the CIRM board, Brown, Controller John Chiang, Treasurer Bill Lockyer and Lt. Gov. Gavin Newsom said they wanted to wait until possibly May 23.
The CIRM governing board on March 14 asked that | | | | | | | | | | | | | | | | | | | | | | | | California state Treasurer Bill Lockyer has confirmed that there is a reasonable possibility that the California stem cell agency will not be able to access new funds until sometime next year.
In a report in the Los Angeles Times yesterday, Lockyer said that sale of all state bonds could be delayed because of inaction on California's state budget woes. State bonds are the only real funding | | | | | | | | | | | | | | | | | | | | | | | | | An item on March 24, 2011, incorrectly said that Duane Roth, co-vice chair of the California stem cell agency, signed the letter proposing the use of private donor funds for the salary of the new chair. The item should have said the letter was signed by Ted Love, chair of the board's evaluation subcommittee. | | | | | | | | | | | | | | | | | | | | | | | | | [Transplantation of Corneal Endothelium - Chances and Challenges.] Klin Monbl Augenheilkd. 2011 Mar 23; Authors: Engelmann K, Valtink M, Lindemann D, Nitschke M BACKGROUND: Endothelial keratoplasty is a promising surgical procedure which may replace penetrating keratoplasty in cases of endothelial cell diseases of the cornea. This method may thereby help to prevent postoperative astigmatism and transplant rejection. METHODS AND RESULTS: A survey of publications reporting about results after endothelial keratoplasty shows that the main problem of this transplantation technique is a postoperative endothelial cell loss which is comparable to or even higher than that observed in penetrating keratoplasty. Improving surgical techniques led to a reduction of the endothelial cell loss, however, cell-based strategies to prevent postoperative cell loss or to enhance the cell densities of donor corneas or endothelial lamellae are rare. DISCUSSION: This review presents an overview of clinical results after endothelial keratoplasty. Current strategies in the field of cell biology and tissue cultivation of corneal endothelial cells, genetic manipulation of the corneal endothelium and tissue engineering strategies aiming at the production of transplantable endothelial cell sheets are described. CONCLUSION: The limited availability of donor corneas makes it mandatory to develop methods in the field of tissue engineering in order to improve corneal endothelial cell survival or to increase corneal endothelial cell density, using interdisciplinary approaches. PMID: 21432765 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Progress of tissue engineering research in vascularized tissue engineering chamber in vivo]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 Feb;25(2):193-7 Authors: Hao X, Yi C, Guo S To introduce a new method of tissue engineering research by transplanting vessels to tissue engineering chamber (vascularized tissue engineering chamber) in vivo, and to review the progress of research in vascularized tissue engineering chamber. PMID: 21427849 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Isolation and growth of adipose tissue-derived stem cells. Methods Mol Biol. 2011;698:37-49 Authors: Zachar V, Rasmussen JG, Fink T Fat tissue provides a rich and easily accessible supply of stem cells that feature the general differentiation potential and plasticity of mesenchymal stem cells. These stem cells, variably designated adipose-derived stem cells (ASCs), hold a great promise for regeneration in vivo and tissue engineering. In order to be able to obtain ASC preparations suitable for basic investigations as well as development of future therapeutic protocols, it is important that the critical isolation steps are properly carried out. Here, we describe in detail enzyme-based procedure for isolation and propagation of ASCs from the human subcutaneous fat tissue that is also adoptable to several animal species. The critical steps and impact of possible modifications on the final outcome are discussed, and useful hints are provided to streamline the troubleshooting. PMID: 21431509 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Preparation of recombinant human bone morphogenetic protein 2 decorated beta tricalcium phosphate/collagen and preliminary studies on its properties of inducing tooth formation]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 Feb;25(2):149-54 Authors: Zhang W, Liu J, Wang H, Li Z To explore a novel nanometer biomaterial which could induce the regeneration of tooth tissues intelligently, and to evaluate the feasibility of using this kind of biomaterial as the scaffold for tooth tissue engineering by investigating the role it plays in tooth tissue engineering. PMID: 21427841 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Standardized Isolation of Human Mesenchymal Stromal Cells with Red Blood Cell Lysis. Methods Mol Biol. 2011;698:23-35 Authors: Horn P, Bork S, Wagner W Human mesenchymal stromal cells (MSC) raise high hopes for tissue engineering and therapeutic -applications. So far, it is not possible to isolate pure fractions from bone marrow and therefore MSC cell preparations notoriously represent heterogeneous mixtures of different cell types. The composition of -subpopulations can already be affected by the initial steps of cell preparation. Usually, isolation of MSC involves density fractionation to separate the mononuclear cells (MNCs) from erythrocytes and -granulocytes. However, this method is difficult to standardize especially under GMP conditions. Here, we describe an alternative approach for isolation of human MSC based on red blood cell (RBC) lysis with ammonium chloride. This results in a slightly higher number of fibroblastic colony forming units (CFU-F), whereas morphological analysis of the CFU-F reveals the same heterogeneous composition of MSC cultures indicating that the proportion of subpopulations is not affected by RBC lysis. Immunophenotype (CD73(+), CD90(+), CD105(+), CD31(-), CD34(-), CD45(-)), adipogenic, and osteogenic differentiation potential of MSC were also similar with both methods. In conclusion, RBC lysis comprises an efficient method for the isolation of human MSC from bone marrow aspirate. This technique is faster and can be standardized more easily for clinical application of MSC. PMID: 21431508 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Experimental study of subcutaneous osteogenesis by bone marrow stromal cells with A-PCPC in Beagle dogs.] Shanghai Kou Qiang Yi Xue. 2010 Dec;19(6):641-646 Authors: Han XS, Tan LJ, Huang YL, Wang L, Liu TL, Zhang XL PURPOSE: To study the osteogenic capability of the construct combined dog's bone stromal cells with active porous calcium phosphate cement (A-PCPC) in nude mice in vivo. METHODS: Isolated bone marrow stromal cells (BMSCs) were expanded and osteogenically induced in vitro. Their osteogenic phenotype was evaluated by cytochemistry. The tissue engineering complex was constructed with BMSCs/A-PCPC in vitro. After SEM scanning, the complex of BMSCs/A-PCPC was implanted into the subcutaneous tissue of the nude mice as experimental group, and A-PCPC as control group. The engineered bone was harvested 2,4,8weeks post-implantation and processed for HE staining, then evaluated by histology and histomorphometry. RESULTS: Cytochemistry showed alkaline phosphate activity, Von Kossa staining proved the formation of mineralization nodules. Scanning electron microscopy showed the cells adhered to the inner surface of the A-PCPC. HE staining showed a small group of woven bone formation 2 weeks later in the experimental group, while the formation of bone less in the control group. Woven bone turned into trabecular bone gradually at 4 weeks in the experimental group, while the control group showed a large number of bone-like tissue. Histomorphometry showed more mature bone in the experimental group than the control group at 8 weeks. CONCLUSIONS: The A-PCPC/BMSCs composites show good osteogenetic activity and could promote mineralization of the immature bone. It can be used as the bone tissue engineering scaffolds. Supported by Innovation Fund for Science and Technology Development of Pudong New District(Grant No. PKJ2009-Y19). PMID: 21431267 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Development and characterization of reinforced poly(L: -lactide) scaffolds for bone tissue engineering. J Mater Sci Mater Med. 2011 Mar 24; Authors: Park JE, Todo M Novel reinforced poly(L: -lactic acid) (PLLA) scaffolds such as solid shell, porous shell, one beam and two beam reinforced scaffolds were developed to improve the mechanical properties of a standard PLLA scaffold. Experimental results clearly indicated that the compressive mechanical properties such as the strength and the modulus are effectively improved by introducing the reinforcement structures. A linear elastic model consisting of three phases, that is, the reinforcement, the porous matrix and the boundary layer was also introduced in order to predict the compressive moduli of the reinforced scaffolds. The comparative study clearly showed that the simple theoretical model can reasonably predict the moduli of the scaffolds with three phase structures. The failure mechanism of the solid shell and the porous shell reinforced scaffolds under compression were found to be buckling of the solid shell and localized buckling of the struts constructing the pores in the porous shell, respectively. For the beam reinforced scaffolds, on the contrary, the primary failure mechanism was understood to be micro-cracking within the beams and the subsequent formation of the main-crack due to the coalescence of the micro-racks. The biological study was exhibited that osteoblast-like cells, MC3T3-E1, were well adhered and proliferated on the surfaces of the scaffolds after 12 days culturing. PMID: 21431907 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose-derived mesenchymal stem cells in collagen-hyaluronic acid gel composite scaffolds for vocal fold regeneration. Ann Otol Rhinol Laryngol. 2011 Feb;120(2):123-30 Authors: Xu W, Hu R, Fan E, Han D We sought to characterize the changes in the extracellular matrix (ECM) of the lamina propria following the implantation of autologous adipose-derived mesenchymal stem cells (ADSCs) in composite scaffolds in a rabbit vocal fold wound model. PMID: 21391425 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Adhesive interactions between cells and biotinylated phospholipid vesicles in alginate: towards new responsive biomaterials. J Mater Sci Mater Med. 2011 Mar 23; Authors: de Cogan F, Gough JE, Webb SJ Creating tissue-mimetic biomaterials able to deliver bioactive compounds after receipt of a remote and non-invasive trigger has so far proved to be challenging. The possible applications of such "smart" biomaterials are vast, ranging from subcutaneous drug delivery to tissue engineering. Self-assembled phospholipid vesicles (liposomes) have the ability to deliver both hydrophilic and hydrophobic drugs, and controlling interactions between functionalized vesicles and cells within biomaterials is an important step for targeted drug delivery to cells. We report an investigation of the interactions between thermally-sensitive and biotin-coated dipalmitoyl phosphatidylcholine vesicles and 3T3 fibroblast cells. The stability of these vesicles under physiological conditions was assessed and their interaction with the cell membranes of fibroblasts in media and alginate/fibronectin mixtures was studied. Stable vesicle-cell aggregates were formed in fluid matrices, and could be a model system for improving the delivery of remotely released drugs within vesicle-containing biomaterials. PMID: 21431355 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Experimental study on culture method of human umbilical vein endothelial cells]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 Feb;25(2):139-43 Authors: Cai W, Liang L, Ji P, Zhang W, Zhang Z, Zhang Y, Xiao X, Bai X, Zhu H, Hu D, Han H To establish an efficient and stable culture method of human umbilical vein endothelial cells (HUVECs) in vitro so as to provide good source of seed cells for tissue engineered vascular grafts and for preclinical research. PMID: 21427839 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Preliminary study on polyvinyl alcohol/wild antheraea pernyi silk fibroin as nanofiber scaffolds for tissue engineered tendon]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 Feb;25(2):181-6 Authors: Wu L, Li M, Zhao J, Chen D, Zhou Z To investigate the cellular compatibility of polyvinyl alcohol (PVA)/wild antheraea pernyi silk fibroin (WSF), and to explore the feasibility for tendon tissue engineering scaffold in vitro. PMID: 21427847 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Use of Human Mesenchymal Stem Cells as Alternative Source of Smooth Muscle Cells in Vessel Engineering. Methods Mol Biol. 2011;698:279-294 Authors: Gong Z, Niklason LE Adult stem cell-derived smooth muscle cells (SMC) may be a promising source of cells for applications in regenerative medicine, including cardiovascular tissue engineering. Primary SMC from native vessels may have limited proliferative capacity and reduced collagen production when sourced from elderly donors, who are the patients in need of vascular grafts due to coronary disease or peripheral arterial disease. Our recent work showed that the ability of human bone marrow-derived mesenchymal stem cells (hMSCs) to differentiate into SMC was modulated by various growth factors, matrix proteins, and mechanical forces. In addition, the components of the culture medium play a very important role in SMC differentiation from hMSCs. In this chapter, we will summarize our experience with the impact of various factors on SMC differentiation from hMSCs. Based upon our findings regarding growth factors, cyclic strain and matrix proteins, a two-phase vessel regeneration culture protocol including a 4-week proliferation phase and a 4-week differentiation phase was developed to optimize proliferation and SMC differentiation of hMSCs consecutively. PMID: 21431526 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Recent progress of researches in cartilage tissue engineering]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 Feb;25(2):187-92 Authors: Jin X To review the recent progress of the researches in the field of cartilage tissue engineering, and to discuss the challenges in construction of tissue engineered cartilage. PMID: 21427848 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Fabrication of novel PLA/CDHA bionanocomposite fibers for tissue engineering applications via electrospinning. J Mater Sci Mater Med. 2011 Mar 24; Authors: Zhou H, Touny AH, Bhaduri SB The main theme here is to fabricate PLA (poly lactic-acid)/CDHA (carbonated calcium deficient hydroxyapatite) bionanocomposites, where both the constituents are biocompatible and biodegradable with one dimension in nanometer scale. Such materials are important in tissue engineering applications. The bionanocomposite fibers were fabricated via electrospinning. There are two important signatures of this paper. First, CDHA, rather than HA, is added to PLA as the second phase. As opposed to HA, CDHA mimics the bone mineral composition better and is biodegradable. Therefore, PLA/CDHA fibers should have better biodegradability while maintaining a physiological pH during degradation. To the best of our knowledge, this is the first attempt of electrospinning of such a composite. Second, the CDHA nanoparticles were synthesized using the benign low temperature biomimetic technique, the only route available for the retention of carbonate ions in the HA lattice. The structural properties, degradation behavior, bioactivity, cell adhesion, and growth capability of as-fabricated PLA/CDHA bionanocomposites were investigated. The results show that the incorporation of CDHA decreased PLA fiber diameters, accelerated PLA degradation, buffered pH decrease caused by PLA degradation, improved the bioactivity and biocompatibility of the scaffold. These results prove that PLA/CDHA bionanocomposites have the potential in tissue regeneration applications. PMID: 21431905 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Osteogenic Differentiation of Human Multipotent Mesenchymal Stromal Cells. Methods Mol Biol. 2011;698:201-214 Authors: Gupta DM, Panetta NJ, Longaker MT A comprehensive knowledge of the molecular biology underlying osteogenic differentiation in a controlled, laboratory setting may promise optimization of future cell-based tissue engineering strategies for clinical problems. The scope of this review encompasses a discussion of the methodology utilized to perform such studies. Our laboratory routinely performs both in vitro and in vivo assays underlying osteogenic differentiation, and the widespread use of singular methodology across multiple investigators and institutions promises great advancements for the skeletal tissue engineering community. PMID: 21431521 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Scientists report progress on engineered blood vessels. JAMA. 2011 Mar 23;305(12):1187 Authors: Hampton T PMID: 21427368 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Tuning electrospinning parameters for production of 3D-fiber-fleeces with increased porosity for soft tissue engineering applications. Eur Cell Mater. 2011;21:286-303 Authors: Milleret V, Simona B, Neuenschwander P, Hall H Degrapol® and PLGA electrospun fiber fleeces were characterized with regard to fiber diameter, alignment, mechanical properties as well as scaffold porosity. The study showed that electrospinning parameters affect fiber diameter and alignment in an inverse relation: fiber diameter was increased with increased flow rate, with decrease in working distance and collector velocity, whereas fiber alignment increased with the working distance and collector velocity but decreased with increased flow rate. When Degrapol® or PLGA-polymers were co-spun with increasing ratios of a water-soluble polymer that was subsequently removed; fibrous scaffolds with increased porosities were obtained. Mechanical properties correlated with fiber alignment rather than fiber diameter as aligned fiber scaffolds demonstrated strong mechanical anisotropy. For co-spun fibers the Young's modulus correlated inversely with the amount of co-spun polymer. Cell proliferation was independent of the porosity of the scaffold, but different between the two polymers. Furthermore, fibrous scaffolds with different porosities were analyzed for cell infiltration suggesting that cell infiltration was enhanced with increased porosity and increasing time. These experiments indicate that 3D-fiber fleeces can be produced with controlled properties, being prerequisites for successful scaffolds in tissue engineering applications. PMID: 21432783 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells: tips and tricks. Methods Mol Biol. 2011;698:253-78 Authors: Solchaga LA, Penick KJ, Welter JF It is well known that adult cartilage lacks the ability to repair itself; this makes articular cartilage a very attractive target for tissue engineering. The majority of articular cartilage repair models attempt to deliver or recruit reparative cells to the site of injury. A number of efforts are directed to the characterization of progenitor cells and the understanding of the mechanisms involved in their chondrogenic differentiation. Our laboratory has focused on cartilage repair using mesenchymal stem cells and studied their differentiation into cartilage. Mesenchymal stem cells are attractive candidates for cartilage repair due to their osteogenic and chondrogenic potential, ease of harvest, and ease of expansion in culture. However, the need for chondrogenic differentiation is superposed on other technical issues associated with cartilage repair; this adds a level of complexity over using mature chondrocytes. This chapter will focus on the methods involved in the isolation and expansion of human mesenchymal stem cells, their differentiation along the chondrogenic lineage, and the qualitative and quantitative assessment of chondrogenic differentiation. PMID: 21431525 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Influence of aligned electrospinning poly (propylene carbonate) on axonal growth of dorsal root ganglion in vitro]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 Feb;25(2):171-5 Authors: Zhao Z, Wang Y, Peng J, Qi H, Zhao B, Zhang L, Huang J, Xu W, Lu S Poly (propylene carbonate) (PPC), a newly reported polymer, has good biodegradability and biocompatibility. To explore the feasibility of using electrospinning PPC materials in nerve tissue engineering, and to observe the effect of aligned and random PPC materials on axonal growth of rat dorsal root ganglions (DRGs) in vitro. PMID: 21427845 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Microstructured platforms to study nanotube-mediated long-distance cell-to-cell connections. Biointerphases. 2011 Mar;6(1):22 Authors: Abel MP, Riese SR, Schlicker O, Bukoreshtliev NV, Gerdes HH, Spatz JP, Rustom A Recently, numerous innovative approaches have attempted to overcome the shortcomings of standard tissue culturing by providing custom-tailored substrates with superior features. In particular, tunable surface chemistry and topographical micro- and nanostructuring have been highlighted as potent effectors to control cell behavior. Apart from tissue engineering and the development of biosensors and diagnostic assays, the need for custom-tailored platform systems is accentuated by a variety of complex and poorly characterized biological processes. One of these processes is cell-to-cell communication mediated by tunneling nanotubes (TNTs), the reliable statistical analysis of which is consistently hampered by critical dependencies on various experimental factors, such as cell singularization, spacing, and alignment. Here, the authors developed a microstructured platform based on a combination of controlled surface chemistry along with topographic parameters, which permits the controllable attachment of different cell types to complementary patterns of cell attracting/nonattracting surface domains and-as a consequence-represents a standardized analysis tool to approach a wide range of biological questions. Apart from the technical complementation of mainstream applications, the developed surfaces could successfully be used to statistically determine TNT-based intercellular connection processes as they are occurring in standard as well as primary cell cultures. PMID: 21428692 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Isolation, Culture, and Characterization of Human Umbilical Cord Stroma-derived Mesenchymal Stem Cells. Methods Mol Biol. 2011;698:51-62 Authors: Can A, Balci D As the collection and isolation of human bone marrow-derived mesenchymal stem cells (MSCs) require invasive and often undesirable procurement procedures, investigators have begun to seek alternative sources of human MSC including the umbilical cord stroma. Here we describe the noninvasive isolation, culture, and basic characterization of human umbilical cord stroma-derived mesenchymal stem cells (hUCS-MSCs). Although some technical and observational variations exist between laboratories, there has been a relatively common consensus regarding the immunological and functional characteristics of hUCS-MSCs. Successful in vitro and in vivo differentiation to several lineages makes these cells an invaluable stem cell source, deserving further testing as a cellular therapy or other applications in regenerative medicine. Therefore, the isolation and culture of hUCS-MSCs still need better clarification to ultimately build an optimal standard procedure among laboratories, tissue banks, and clinics. PMID: 21431510 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Two-photon lithography in the future of cell-based therapeutics and regenerative medicine: a review of techniques for hydrogel patterning and controlled release. Future Med Chem. 2010 Nov;2(11):1669-80 Authors: Kasko AM, Wong DY In recent decades, there has been considerable interest in using photochemistry to produce biomaterials, owing to their ability to be used in the presence of biological material. Two-photon-induced photoreactions have been used to produce materials for optical data storage and microfabrication and, recently, researchers have exploited two-photon-induced chemical processes to create biomaterials. Researchers have used two-photon-induced lithography to fabricate hydrogels with well-defined chemical and physical properties in 3D through network polymerization, functionalization, uncaging and degradation, as described in this article. Fabrication and modification of chemical and physical architecture of biomaterials in 3D with submicron resolution will allow the elucidation of more complex relationships in cell behavior and tissue development and introduce pathways to engineering complex tissues. PMID: 21428838 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Cell fusion and tissue regeneration. Adv Exp Med Biol. 2011;713:161-75 Authors: Alvarez-Dolado M, Martínez-Losa M Cell fusion is a natural process implicated in normal development, immune response, tissue formation, and with a prominent role in stem cell plasticity. The discovery that bone marrow stem cells fuse with several cell types, under normal condition or after an injury, introduces new possibilities in regenerative medicine and genetic repair. Cell fusion has been shown to be implicated in regeneration, and the complementation of recessive mutations affecting the liver, brain, muscle, lung and gut, under appropriate conditions. However, we should be cautious and better understand the mechanisms that govern cell fusion during regeneration before to consider it as clinically relevant. In this chapter, we will present the current evidences about the role of cell fusion in tissue regeneration and its future potential as therapy. Cell fusion is an exciting and promising research field. In addition, we will review the challenges that should face the fusion process to become therapeutically effective and safe. PMID: 21432019 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration and function. Hepatology. 2011 Mar 23; Authors: Thomas JA, Pope C, Wojtacha D, Robson AJ, Gordon-Walker TT, Hartland S, Ramachandran P, Van Deemter M, Hume DA, Iredale JP, Forbes SJ Clinical studies of bone marrow (BM) cell therapy for liver cirrhosis are underway but the mechanisms of benefit remain undefined. Cells of the monocyte-macrophage lineage have key roles in the development and resolution of liver fibrosis. Therefore, we have tested the therapeutic effects of these cells on murine liver fibrosis. Advanced liver fibrosis was induced in female mice by chronic administration of carbon tetrachloride. Unmanipulated, syngeneic macrophages, their specific BM precursors or unfractionated BM cells were delivered during liver injury. Mediators of inflammation, fibrosis and regeneration were measured. Donor cells were tracked by sex-mismatch and green fluorescent protein expression. BM-derived macrophage (BMM) delivery resulted in early chemokine upregulation with hepatic recruitment of endogenous macrophages and neutrophils. These cells delivered matrix metalloproteinases-13 and -9 respectively, into the hepatic scar. The effector cell infiltrate was accompanied by increased levels of the anti-inflammatory cytokine IL-10. A reduction in hepatic myofibroblasts was followed by reduced fibrosis detected 4 weeks after macrophage infusion. Serum albumin levels were elevated at this time. Upregulation of the liver progenitor cell mitogen TWEAK preceded expansion of the progenitor cell compartment. Increased expression of colony stimulating factor-1, insulin-like growth factor-1 and vascular endothelial growth factor also followed BMM delivery. In contrast to the effects of differentiated macrophages, liver fibrosis was not significantly altered by the application of macrophage precursors and was exacerbated by whole BM. Conclusion: Macrophage cell therapy improves clinically relevant parameters in experimental chronic liver injury. Paracrine signaling to endogenous cells amplifies the effect. The benefits from this single, defined cell type suggest clinical potential. (HEPATOLOGY 2011.). PMID: 21433043 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose-derived Stromal Vascular Fraction Cells and Stem Cells: Let's Not Get Lost in Translation. Stem Cells. 2011 Mar 23; Authors: Gimble JM, Bunnell BA, Chiu ES, Guilak F Subcutaneous fat has emerged as an alternative tissue source for stromal/stem cells in regenerative medicine. Over the past decade, international research efforts have established a wealth of basic science and pre-clinical evidence regarding the differentiation potential and regenerative properties of both freshly processed, heterogeneous stromal vascular fraction (SVF) cells and culture expanded, relatively homogeneous adipose-derived stromal/stem cells (ASCs). The stage has been set for clinicians to translate adipose-derived cells from the bench to the bedside; however, this process will involve "development" steps that fall outside of traditional "hypothesis-driven, mechanism-based" paradigm. This concise review examines the next stages of the "development" process for therapeutic applications of adipose-derived cells and highlights the current state of the art regarding clinical trials. It is recommended that the experiments addressing these issues be reported comprehensively in the peer-review literature. This transparency will accelerate the standardization and reproducibility of adipose-derived cell therapies with respect to their efficacy and safety. PMID: 21433220 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cell-fusion-mediated reprogramming: pluripotency or transdifferentiation? Implications for regenerative medicine. Adv Exp Med Biol. 2011;713:137-59 Authors: Sanges D, Lluis F, Cosma MP Cell-cell fusion is a natural process that occurs not only during development, but as has emerged over the last few years, also with an important role in tissue regeneration. Interestingly, in-vitro studies have revealed that after fusion of two different cell types, the developmental potential of these cells can change. This suggests that the mechanisms by which cells differentiate during development to acquire their identities is not irreversible, as was considered until a few years ago. To date, it is well established that the fate of a cell can be changed by a process known as reprogramming. This mainly occurs in two different ways: the differentiated state of a cell can be reversed back into a pluripotent state (pluripotent reprogramming), or it can be switched directly to a different differentiated state (lineage reprogramming). In both cases, these possibilities of obtaining sources of autologous somatic cells to maintain, replace or rescue different tissues has provided new and fundamental insights in the stem-cell-therapy field. Most interestingly, the concept that cell reprogramming can also occur in vivo by spontaneous cell fusion events is also emerging, which suggests that this mechanism can be implicated not only in cellular plasticity, but also in tissue regeneration. In this chapter, we will summarize the present knowledge of the molecular mechanisms that mediate the restoration of pluripotency in vitro through cell fusion, as well as the studies carried out over the last 3 decades on lineage reprogramming, both in vitro and in vivo. How the outcome of these studies relate to regenerative medicine applications will also be discussed. PMID: 21432018 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Controlling embryonic stem cell proliferation and pluripotency: the role of PI3K- and GSK-3-dependent signalling. Biochem Soc Trans. 2011 Apr 1;39(2):674-8 Authors: Welham MJ, Kingham E, Sanchez-Ripoll Y, Kumpfmueller B, Storm M, Bone H ESCs (embryonic stem cells) are derived from the inner cell mass of pre-implantation embryos and are pluripotent, meaning they can differentiate into all of the cells that make up the adult organism. This property of pluripotency makes ESCs attractive as a model system for studying early development and for the generation of specific cell types for use in regenerative medicine and drug screening. In order to harness their potential, the molecular mechanisms regulating ESC pluripotency, proliferation and differentiation (i.e. cell fate) need to be understood so that pluripotency can be maintained during expansion, while differentiation to specific lineages can be induced accurately when required. The present review focuses on the potential roles that PI3K (phosphoinositide 3-kinase) and GSK-3 (glycogen synthase kinase 3)-dependent signalling play in the co-ordination and integration of mouse ESC pluripotency and proliferation and contrast this with our understanding of their functions in human ESCs. PMID: 21428960 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Two Dimensional Gel Electrophoresis Analysis of Mesenchymal Stem Cells. Methods Mol Biol. 2011;698:431-442 Authors: Provansal M, Jorgensen C, Lehmann S, Roche S Proteomic analysis is a powerful tool to follow physiological modifications and phenotypes of mesenchymal stem cells (MSC). This approach generates informative data on expression and post-translational modifications of proteins which are of interest to assess the true potential of MSC in regenerative medicine. No matter the technologies used, proteomic analysis is always a challenge as the proteome is extremely diverse (in terms of constituents and concentrations), is changing with time, and is highly sensitive to pre-analytical conditions. In the framework of a European project (GENOSTEM http://www.genostem.org/ ), we have set up a multisite two dimensional gel electrophoresis (2DE) proteomic comparison of MSC. The goal is to compare cells from different origins, to follow their differentiation and to ultimately define a specific MSC proteomic signature. One important initial task is the optimization of 2DE protocols such that they are robust enough to be used in a multisite project. In this chapter, we detail these protocols which can be used not only for MSC but also for other cells in culture. PMID: 21431536 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Identity, Fate and Potential of Cells Grown as Neurospheres: Species Matters. Stem Cell Rev. 2011 Mar 24; Authors: Steffenhagen C, Kraus S, Dechant FX, Kandasamy M, Lehner B, Poehler AM, Furtner T, Siebzehnrubl FA, Couillard-Despres S, Strauss O, Aigner L, Rivera FJ It is commonly accepted that adult neurogenesis and gliogenesis follow the same principles through the mammalian class. However, it has been reported that neurogenesis might differ between species, even from the same order, like in rodents. Currently, it is not known if neural stem/progenitor cells (NSPCs) from various species differ in their cell identity and potential. NSPCs can be expanded ex vivo as neurospheres (NSph), a model widely used to study neurogenesis in vitro. Here we demonstrate that rat (r) and mouse (m) NSph display different cell identities, differentiation fate, electrophysiological function and tumorigenic potential. Adult rNSph consist mainly of oligodendroglial progenitors (OPCs), which after repeated passaging proliferate independent of mitogens, whereas adult mNSph show astroglial precursor-like characteristics and retain their mitogen dependency. Most of the cells in rNSph express OPC markers and spontaneously differentiate into oligodendrocytes after growth factor withdrawal. Electrophysiological analysis confirmed OPC characteristics. mNSph have different electrophysiological properties, they express astrocyte precursor markers and spontaneously differentiate primarily into astrocytes. Furthermore, rNSph have the potential to differentiate into oligodendrocytes and astrocytes, whereas mNSph are restricted to the astrocytic lineage. The phenotypic differences between rNSph and mNSph were not due to a distinct response to species specific derived growth factors and are probably not caused by autocrine mechanisms. Our findings suggest that NSph derived from adult rat and mouse brains display different cell identities. Thus, results urge for caution when data derived from NSph are extrapolated to other species or to the in vivo situation, especially when aimed towards the clinical use of human NSph. PMID: 21431886 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal stem cell assays and applications. Methods Mol Biol. 2011;698:3-8 Authors: Vemuri MC, Chase LG, Rao MS Research on mesenchymal stem cells (MSC) is progressing with increasing popularity. Currently there are a significant number of clinical trials exploring the use of MSCs for the treatment of various diseases including graft-versus-host disease, Crohn's disease, myocardial infarction, stroke, bone defects, diabetes, and wound repair (www.-clinicaltrails.gov). At the same time, there are questions associated with MSCs in terms of their isolation, culture expansion, phenotype, multipotential differentiation, and transplantation efficiency. This chapter outlines the current status of the field and emphasizes the need for clearly defined protocols to better define the function and use of MSCs in cell therapy. PMID: 21431506 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine: a snapshot of the current regulatory environment and standards. Adv Mater. 2011 Mar 25;23(12):H10-7 Authors: Messenger MP, Tomlins PE PMID: 21433095 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Dynamic Expansion Culture for Mesenchymal Stem Cells. Methods Mol Biol. 2011;698:175-188 Authors: Majd H, Quinn TM, Wipff PJ, Hinz B To be applied in sufficient numbers for regenerative medicine, primary mesenchymal stem cells (MSCs) need to be amplified in culture. Standard cell culture involves regular passing because MSC proliferation in size-limited culture vessels stagnates due to contact inhibition of growth. The use of harmful enzymes for passaging and the mechanical properties of standard culture vessels change the MSC phenotype. Initially, fast growing multipotent and regenerative MSCs will turn into slowly growing cells with reduced multipotency and fibrotic character. We here describe an innovative culture system that maintains overall constant cell densities which are near-optimal for proliferation, while preventing contact-inhibition of cell growth. This is achieved by dynamically enlarging a novel highly elastic culture dish using a motorized mechanical device and adapting the culture surface to the increasing cell numbers. Dynamic MSC culture expansion reduces the number of enzymatic passages by a factor of 3 and delivers higher MSC yields than conventional culture. On the expanded culture surface, MSCs maintain stem cell characteristics and high growth rates over months and are still inducible to follow different lineages thereafter. PMID: 21431519 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | PC3 is a cell line characteristic of prostatic small cell carcinoma. Prostate. 2011 Mar 22; Authors: Tai S, Sun Y, Squires JM, Zhang H, Oh WK, Liang CZ, Huang J BACKGROUND: The majority of the prostatic cancers are adenocarcinomas characterized by glandular formation and the expression of luminal differentiation markers androgen receptor (AR) and prostate-specific antigen (PSA). Most adenocarcinomas are indolent and androgen-dependent. Hormonal therapy that inhibits AR signaling produces symptomatic relief in patients with advanced and metastatic adenocarcinomas. Prostatic small cell neuroendocrine carcinoma (SCNC) is a variant form of prostate cancer (PC). In contrast to adenocarcinoma, the tumor cells of SCNC do not form glands and are negative for AR and PSA. SCNC is extremely aggressive and does not respond to hormonal therapy. The purpose of this study was to compare the important and relevant features of two most commonly used PC cell lines, LNCaP and PC3, with prostatic adenocarcinoma and SCNC. METHODS: Xenograft tumors of LNCaP and PC3 were prepared and compared with human prostatic adenocarcinoma and SCNC for the expression of key signaling molecules by immunohistochemistry and Western blot analysis. RESULTS: LNCaP cells express AR and PSA and their growth is inhibited by androgen withdrawal, similar to human prostatic adenocarcinoma. PC3 cells do not express AR and PSA and their proliferation is independent of androgen, similar to SCNC. Adenocarcinoma cells and LNCaP cells are negative for neuroendocrine markers and stem cell-associated marker CD44 while SCNC and PC3 cells are positive. LNCaP cells have identical cytokeratin profiles to adenocarcinoma while PC3 cells have cytokeratin profiles similar to SCNC. CONCLUSION: LNCaP cells share common features with adenocarcinoma while PC3 cells are characteristic of SCNC. Prostate © 2011 Wiley-Liss, Inc. PMID: 21432867 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Use of Human Mesenchymal Stem Cells as Alternative Source of Smooth Muscle Cells in Vessel Engineering. Methods Mol Biol. 2011;698:279-294 Authors: Gong Z, Niklason LE Adult stem cell-derived smooth muscle cells (SMC) may be a promising source of cells for applications in regenerative medicine, including cardiovascular tissue engineering. Primary SMC from native vessels may have limited proliferative capacity and reduced collagen production when sourced from elderly donors, who are the patients in need of vascular grafts due to coronary disease or peripheral arterial disease. Our recent work showed that the ability of human bone marrow-derived mesenchymal stem cells (hMSCs) to differentiate into SMC was modulated by various growth factors, matrix proteins, and mechanical forces. In addition, the components of the culture medium play a very important role in SMC differentiation from hMSCs. In this chapter, we will summarize our experience with the impact of various factors on SMC differentiation from hMSCs. Based upon our findings regarding growth factors, cyclic strain and matrix proteins, a two-phase vessel regeneration culture protocol including a 4-week proliferation phase and a 4-week differentiation phase was developed to optimize proliferation and SMC differentiation of hMSCs consecutively. PMID: 21431526 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Comparison of Microarray and Quantitative Real-Time PCR Methods for Measuring MicroRNA Levels in MSC Cultures. Methods Mol Biol. 2011;698:419-429 Authors: Camarillo C, Swerdel M, Hart RP The capacity for self-renewal and the multilineage potential of mesenchymal stromal cells (MSC) offer a therapeutic promise for regenerative medicine. MicroRNAs (miRNAs) are small noncoding RNAs that play a key regulatory role during differentiation both at the level of posttranslational modulation and epigenetic control. Studies on MSCs have just begun to identify miRNA profiles in MSC and differentiated MSC. While several methods are available for miRNA exploration, microarrays and quantitative real-time PCR (qPCR) are the most common. Since there are several microarray and qPCR platforms available for miRNA detection, it is valuable to explore how these methods compare. We used the NCode Multi-Species miRNA microarray (Invitrogen) and the TaqMan Human microRNA array (Applied Biosystems) to compare microRNA expression in undifferentiated MSCs and MSCs differentiated into early osteoblasts. We show that while there is a somewhat low correlation between these two methods, there is a subset of miRNA measurements that did correlate. PMID: 21431535 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Gene expression in primary cultured astrocytes affected by aluminum: alteration of chaperons involved in protein folding. Environ Health Prev Med. 2011 Jan;16(1):16-24 Authors: Aremu DA, Ezomo OF, Meshitsuka S Aluminum is notorious as a neurotoxic metal. The aim of our study was to determine whether endoplasmic reticulum (ER) stress is involved in aluminum-induced apoptosis in astrocytes. PMID: 21432213 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Human Mesenchymal Stem Cells Reprogram Adult Cardiomyocytes Towards a Progenitor-Like State Through Partial Cell Fusion and Mitochondria Transfer. Stem Cells. 2011 Mar 23; Authors: Acquistapace A, Bru T, Lesault PF, Figeac F, Coudert AE, le Coz O, Christov C, Baudin X, Auber F, Yiou R, Dubois-Randé JL, Rodriguez AM Because stem cells are often found to improve repair tissue including heart without evidence of engraftment or differentiation, mechanisms underlying wound healing are still elusive. Several studies have reported that stem cells can fuse with cardiomyocytes either by permanent or partial cell fusion processes. However, the respective physiological impact of these 2 processes remains unknown in part because of the lack of knowledge of the resulting hybrid cells. To further characterize cell fusion, we co-cultured mouse fully differentiated cardiomyocytes with human multipotent adipose-derived stem cells (hMADS cells) as a model of adult stem cells. We found that heterologous cell fusion promoted cardiomyocyte reprogramming back to a progenitor-like state. The resulting hybrid cells expressed early cardiac commitment and proliferation markers such as GATA-4, myocyte enhancer factor 2C, Nkx2.5 and Ki67 and exhibited a mouse genotype. Interestingly, human bone-marrow derived stem cells shared similar reprogramming properties than hMADS cells but not human fibroblasts, which suggests that these features might be common to multipotent cells. Furthermore, cardiac hybrid cells were preferentially generated by partial rather than permanent cell fusion and that intercellular structures composed of f-actin and microtubule filaments were involved in the process. Finally, we showed that stem cell mitochondria were transferred into cardiomyocytes, persisted in hybrids and were required for somatic cell reprogramming. In conclusion, by providing new insights into previously reported cell fusion processes, our data might contribute to a better understanding of stem cell-mediated regenerative mechanisms and thus, the development of more efficient stem cell-based heart therapies. PMID: 21433223 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose-derived Stromal Vascular Fraction Cells and Stem Cells: Let's Not Get Lost in Translation. Stem Cells. 2011 Mar 23; Authors: Gimble JM, Bunnell BA, Chiu ES, Guilak F Subcutaneous fat has emerged as an alternative tissue source for stromal/stem cells in regenerative medicine. Over the past decade, international research efforts have established a wealth of basic science and pre-clinical evidence regarding the differentiation potential and regenerative properties of both freshly processed, heterogeneous stromal vascular fraction (SVF) cells and culture expanded, relatively homogeneous adipose-derived stromal/stem cells (ASCs). The stage has been set for clinicians to translate adipose-derived cells from the bench to the bedside; however, this process will involve "development" steps that fall outside of traditional "hypothesis-driven, mechanism-based" paradigm. This concise review examines the next stages of the "development" process for therapeutic applications of adipose-derived cells and highlights the current state of the art regarding clinical trials. It is recommended that the experiments addressing these issues be reported comprehensively in the peer-review literature. This transparency will accelerate the standardization and reproducibility of adipose-derived cell therapies with respect to their efficacy and safety. PMID: 21433220 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Isolation and growth of adipose tissue-derived stem cells. Methods Mol Biol. 2011;698:37-49 Authors: Zachar V, Rasmussen JG, Fink T Fat tissue provides a rich and easily accessible supply of stem cells that feature the general differentiation potential and plasticity of mesenchymal stem cells. These stem cells, variably designated adipose-derived stem cells (ASCs), hold a great promise for regeneration in vivo and tissue engineering. In order to be able to obtain ASC preparations suitable for basic investigations as well as development of future therapeutic protocols, it is important that the critical isolation steps are properly carried out. Here, we describe in detail enzyme-based procedure for isolation and propagation of ASCs from the human subcutaneous fat tissue that is also adoptable to several animal species. The critical steps and impact of possible modifications on the final outcome are discussed, and useful hints are provided to streamline the troubleshooting. PMID: 21431509 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Adipogenic differentiation of human mesenchymal stem cells. Methods Mol Biol. 2011;698:243-51 Authors: Fink T, Zachar V Mesenchymal stem cells have the capability to differentiate into a number of cell types including adipocytes. The adipocytic phenotype is characterized by intracellular accumulation of lipid droplets as well as transcription of adipocyte-specific genes. This paper details a basic protocol for adipogenic induction of bone marrow and adipose tissue-derived stem cells, as well as protocols for staining lipid accumulation and the transcriptional analysis of PPAR-γ and aP2 by real-time RT-PCR. PMID: 21431524 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Genetically modified adipose tissue derived mesenchymal stem cells (AT-MSC) overexpressing CXCR4 display increased motility, invasiveness and homing to bone marrow of NOD/SCID mice. Exp Hematol. 2011 Mar 19; Authors: Bobis-Wozowicz S, Miekus K, Wybieralska E, Jarocha D, Zawisz A, Madeja Z, Majka M OBJECTIVE: This study evaluates usefulness of CXCR4 overexpression, via retroviral transduction, in adipose tissue derived AT-MSC, as a strategy to increase their migration and engraftment ability. METHODS: AT-MSC were isolated from lipoaspirates from human healthy donors with liberase 3. The cells were transduced with retroviral vector carrying either CXCR4 or GFP cDNA and neo resistant colonies were selected and used in experiments. Chemotaxis, invasion through matrigel, motor activity, gene expression, osteodifferentiation potential and engraftment into bone marrow of NOD/SCID mice were analyzed for CXCR4-over-expressing cells and GFP-control cells. RESULTS: Approximately 90% of retrovirus-transduced AT-MSC expressed CXCR4 or GFP and maintained their ability to differentiate into osteocytes. CXCR4-transduced AT-MSC displayed enhanced migration and higher invasiveness toward SDF-1 gradient. The up-regulation of CXCR4 led to phosphorylation of MAP and AKT kinases and an increase in metaloproteinases expression after SDF-1 stimulation. The transplantation of CXCR4-transduced AT-MSC into NOD/SCID mice led to increased engraftment into bone marrow in comparison to GFP-transduced AT-MSC. CONCLUSION: Adipose tissue is one of alternative sources of MSC to bone marrow (BM-MSC). We showed, that AT-MSC overexpressing CXCR4, preserve their ability for osteodifferentiation. Enhanced migration and engraftment of the transduced AT-MSC into bone marrow indicates usefulness of this strategy in overcoming low engraftment of MSC in clinical approaches of cellular therapies for bone disorders and hence may represent a powerful tool in regenerative medicine and gene therapies. Thus, these cells may be used as an alternative to bone marrow derived MSC (BM-MSC). PMID: 21426925 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | REST and CoREST are transcriptional and epigenetic regulators of seminal neural fate decisions. Cell Cycle. 2010 Dec 7;9(22):4477-86 Authors: Qureshi IA, Gokhan S, Mehler MF Complementary transcriptional and epigenetic regulatory factors (e.g., histone and chromatin modifying enzymes and non-coding RNAs) regulate genes responsible for mediating neural stem cell maintenance and lineage restriction, neuronal and glial lineage specification, and progressive stages of lineage maturation. However, an overall understanding of the mechanisms that sense and integrate developmental signals at the genomic level and control cell type-specific gene network deployment has not emerged. REST and CoREST are central players in the transcriptional and epigenetic regulatory circuitry that is responsible for modulating neural genes, and they have been implicated in establishing cell identity and function, both within the nervous system and beyond it. Herein, we discuss the emerging context-specific roles of REST and CoREST and highlight our recent studies aimed at elucidating their neural developmental cell type- and stage-specific actions. These observations support the conclusion that REST and CoREST act as master regulators of key neural cell fate decisions. PMID: 21088488 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Directed embryonic stem cell differentiation with small molecules. Future Med Chem. 2010 Jun;2(6):965-73 Authors: Zhu S, Wurdak H, Schultz PG Embryonic stem cells (ESCs) are a promising cell source for regenerative medicine and transplantation therapy.ESCs are able to self-renew indefinitely in culture; however, the ability to differentiate ESCs into specific cell lineages is key to exploiting their therapeutic potential. Cell-based phenotypic and reporter-based screens have been used to identify small molecules that selectively promote ESC differentiation into a variety of cell lineages. Not only will such molecules facilitate the clinical applications of stem cells, the detailed study of their mechanism is providing new insights into the biology that regulates ESC self-renewal and differentiation. In this article we discuss key issues, challenges and opportunities in the application of this chemical approach to stem cell biology. PMID: 21426114 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Magnetic labeling, imaging and manipulation of endothelial progenitor cells using iron oxide nanoparticles. Future Med Chem. 2010 Mar;2(3):397-408 Authors: Gazeau F, Wilhelm C Endothelial progenitor cells (EPCs), originating from bone marrow, play a significant role in the repair of ischemic tissue and injured blood vessels. They are also involved in tumor angiogenesis. The therapeutic potential of EPCs for regenerative medicine and cancer treatment calls for new methods for monitoring and controlling cell migration. This review focuses on promising magnetic methods based on the internalization of magnetic nanoparticles by EPCs. We first describe the cellular uptake of iron oxide nanoparticles depending on their surface properties. We thus review the use of MRI for the detection of labeled cells and for noninvasive follow-up of EPCs homing in sites of endothelium regeneration. Finally, we show that remotely applied magnetic forces may enable intracellular manipulation and may optimize cell-delivery strategies for localizing cell therapy to target sites. PMID: 21426174 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Reference values of biochemical and hematological parameters for Guizhou minipigs. Exp Biol Med (Maywood). 2011 Mar 22; Authors: Chen Y, Qin S, Ding Y, Li S, Yang G, Zhang J, Li Y, Cheng J, Lu Y The pig is not only an economically important livestock animal but is also a valuable model animal for biomedical research and xenotransplantation. Reference values for clinical biochemical and hematological parameters are required for accurate data interpretation while using a pig model. In this study, whole blood samples were collected from 54 healthy Chinese Guizhou minipigs. We analyzed routine biochemical and hematological parameters and special coagulation parameters, including thrombelastography and coagulation factor activities, and have presented the baseline values of these parameters. These data provide valuable information for investigators using minipigs as animal models in biomedical studies and useful physiological data for veterinarians and livestock producers. We also compared all the results for the minipigs with the corresponding data from healthy humans. The bilirubin, uric acid and cholesterol levels of minipigs were significantly lower than those of humans (14%, 0.086% and 48% of human levels, respectively), whereas the serum enzyme levels were much higher than those in humans (e.g. the hydroxybutyrate dehydrogenase and creatine kinase levels of the minipigs were 19- and 8.4-fold higher than the human reference values). The red blood cell counts, platelet counts and white blood cell counts of the minipigs were significantly higher than those of the humans. The coagulation activities of factor VII and factor X were higher in minipigs than in humans. The significant differences observed between minipigs and humans for many of these parameters suggest substantial interspecies disparities in organs and tissues. These differences merit greater attention in biomedical research involving minipigs, particularly in the area of pig-to-human transplantation. PMID: 21427234 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Transplantation as a subfield of regenerative medicine. Expert Rev Clin Immunol. 2011 Mar;7(2):137-41 Authors: Orlando G Interview by Lauren Constable, Commissioning Editor Giuseppe Orlando, MD, PhD, is a research scientist at the Nuffield Department of Surgical Sciences at the University of Oxford, in quality of Marie Curie International Outgoing Fellow. He obtained his degrees in medicine and general surgery from the Tor Vergata University of Rome (Italy), where he also obtained his PhD in transplant sciences. In addition, he trained at the Liver Unit of the Paul Brousse Hospital (Villejuif, France), at the General Surgery and Liver Transplant Unit of the Cliniques Saint Luc (Brussels, Belgium) and at the Wake Forest Institute for Regenerative Medicine (Winston Salem, NC, USA). He specialized in liver and kidney transplantation, and is currently specializing in engineering and regeneration of transplantable abdominal organs. His main fields of investigation are: minimal immunosuppression and clinical operational tolerance after abdominal organ transplantation; renal, pancreas, liver and intestinal bioengineering; the respinse of the immune system to bioengineered body parts. Dr. Orlando's main achievements have been in the field of steroid-free immunosuppression, immunosuppression minimization and clinical tolerance after liver transplantation and is on the board and a regular reviewer for a number of journals. He has authored or coauthored several research papers, review articles and book chapters on liver and kidney transplantation and regenerative medicine. PMID: 21426251 [PubMed - in process] | | | | | | | | | |  | |  | |  |
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