|
| DNA methylation in cell differentiation and reprogramming: an emerging systematic view.
July 17, 2010 at 8:02 AM
|
| | DNA methylation in cell differentiation and reprogramming: an emerging systematic view. Regen Med. 2010 Jul;5(4):531-44 Authors: Huang K, Fan G Embryonic stem cells have the unique ability to indefinitely self-renew and differentiate into any cell type found in the adult body. Differentiated cells can, in turn, be reprogrammed to embryonic stem-like induced pluripotent stem cells, providing exciting opportunities for achieving patient-specific stem cell therapy while circumventing immunological obstacles and ethical controversies. Since both differentiation and reprogramming are governed by major changes in the epigenome, current directions in the field aim to uncover the epigenetic signals that give pluripotent cells their unique properties. DNA methylation is one of the major epigenetic factors that regulates gene expression in mammals and is essential for establishing cellular identity. Recent analyses of pluripotent and somatic cell methylomes have provided important insights into the extensive role of DNA methylation during cell-fate commitment and reprogramming. In this article, the recent progress of differentiation and reprogramming research illuminated by high-throughput studies is discussed in the context of DNA methylation. PMID: 20632857 [PubMed - in process] | | |
| Rapid Mineralization of Electrospun Scaffolds for Bone Tissue Engineering.
July 17, 2010 at 6:42 AM
|
| | Rapid Mineralization of Electrospun Scaffolds for Bone Tissue Engineering. J Biomater Sci Polym Ed. 2010 Jul 13; Authors: Andric T, Wright LD, Freeman JW We investigated different techniques to enhance calcium phosphate mineral precipitation onto electrospun poly(L-lactide) (PLLA) scaffolds when incubated in concentrated simulated body fluid (SBF), 10xSBF. The techniques included the use of vacuum, pre-treatment with 0.1 M NaOH and electrospinning gelatin/PLLA blends as means to increase overall mineral precipitation and distribution throughout the scaffolds. Mineral precipitation was evaluated using environmental scanning electron microscopy, energy dispersive spectroscopy mapping and the determination of the mineral weight percents. In addition we evaluated the effect of the techniques on mechanical properties, cellular attachment and cellular proliferation on scaffolds. Two treatments, pre-treatment with NaOH and incorporation of 10% gelatin into PLLA solution, both in combination with vacuum, resulted in significantly higher degrees of mineralization (16.55 and 15.14%, respectively) and better mineral distribution on surfaces and through the cross-sections after 2 h of exposure to 10xSBF. While both scaffold groups supported cell attachment and proliferation, 10% gelatin/PLLA scaffolds had significantly higher yield stress (1.73 vs 0.56 MPa) and elastic modulus (107 vs 44 MPa) than NaOH-pre-treated scaffolds. PMID: 20633329 [PubMed - as supplied by publisher] | | |
| Novel strategy to engineer trachea cartilage graft with marrow mesenchymal stem cell macroaggregate and hydrolyzable scaffold.
July 17, 2010 at 6:42 AM
|
| | Novel strategy to engineer trachea cartilage graft with marrow mesenchymal stem cell macroaggregate and hydrolyzable scaffold. Artif Organs. 2010 May;34(5):426-33 Authors: Liu L, Wu W, Tuo X, Geng W, Zhao J, Wei J, Yan X, Yang W, Li L, Chen F Limited donor sites of cartilage and dedifferentiation of chondrocytes during expansion, low tissue reconstruction efficiency, and uncontrollable immune reactions to foreign materials are the main obstacles to overcome before cartilage tissue engineering can be widely used in the clinic. In the current study, we developed a novel strategy to fabricate tissue-engineered trachea cartilage grafts using marrow mesenchymal stem cell (MSC) macroaggregates and hydrolyzable scaffold of polylactic acid-polyglycolic acid copolymer (PLGA). Rabbit MSCs were continuously cultured to prepare macroaggregates in sheet form. The macroaggregates were studied for their potential for chondrogenesis. The macroaggregates were wrapped against the PLGA scaffold to make a tubular composite. The composites were incubated in spinner flasks for 4 weeks to fabricate trachea cartilage grafts. Histological observation and polymerase chain reaction array showed that MSC macroaggregates could obtain the optimal chondrogenic capacity under the induction of transforming growth factor-beta. Engineered trachea cartilage consisted of evenly spaced lacunae embedded in a matrix rich in proteoglycans. PLGA scaffold degraded totally during in vitro incubation and the engineered cartilage graft was composed of autologous tissue. Based on this novel, MSC macroaggregate and hydrolyzable scaffold composite strategy, ready-to-implant autologous trachea cartilage grafts could be successfully fabricated. The strategy also had the advantages of high efficiency in cell seeding and tissue regeneration, and could possibly be used in future in vivo experiments. PMID: 20633157 [PubMed - in process] | | |
| Enhanced chondrogenic responses of human articular chondrocytes onto silk fibroin/wool keratose scaffolds treated with microwave-induced argon plasma.
July 17, 2010 at 6:42 AM
|
| | Enhanced chondrogenic responses of human articular chondrocytes onto silk fibroin/wool keratose scaffolds treated with microwave-induced argon plasma. Artif Organs. 2010 May;34(5):384-92 Authors: Cheon YW, Lee WJ, Baek HS, Lee YD, Park JC, Park YH, Ki CS, Chung KH, Rah DK Silk fibroin (SF) is a natural, degradable, fibrous protein that is biocompatible, is easily processed, and possesses unique mechanical properties. Another natural material, wool keratose (WK), is a soluble derivative of wool keratin, containing amino acid sequences that induce cell adhesion. Here, we blended SF and WK to improve the poor electrospinability of WK and increase the adhesiveness of SF. We hypothesized that microwave-induced argon plasma treatment would improve chondrogenic cell growth and cartilage-specific extracellular matrix formation on a three-dimensional SF/WK scaffold. After argon plasma treatment, static water contact angle measurement revealed increased hydrophilicity of the SF/WK scaffold, and scanning electron microscopy showed that treated SF/WK scaffolds had deeper and more cylindrical pores than nontreated scaffolds. Attachment and proliferation of neonatal human knee articular chondrocytes on treated SF/WK scaffolds increased significantly, followed by increased glycosaminoglycan synthesis. Our results suggest that microwave-induced, plasma-treated SF/WK scaffolds have potential in cartilage tissue engineering. PMID: 20633153 [PubMed - in process] | | |
| [Comparative study on potential of adipogenic differentiation between dedifferentiated adipocytes and adipose-derived stromal cells]
July 17, 2010 at 6:42 AM
|
| | [Comparative study on potential of adipogenic differentiation between dedifferentiated adipocytes and adipose-derived stromal cells] Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2010 Jun;24(6):749-53 Authors: Liao Y, Gao J, Lu F OBJECTIVE: Seed cells are the hotspot of tissue engineering research. To study the seed cells with high potential of adipogenic differentiation for applying the adipose tissue engineering and increasing the constructing efficiency of adipose tissue engineering. METHODS: Mature adipocytes (MA) and adipose-derived stromal cells (ADSCs) were harvested from human fat aspirates via liposuction by collagenase digestion. MA were cultured and induced to dedifferentiated adipocytes (DA) by ceiling adherent culture method. DA and ADSCs were induced to adipogenic differentiation. The adipogenic abilities of DA and ADSCs were compared by inverted phase contrast microscope observation, absorption spectrometry assay of oil red O staining, and cell counting of oil red O staining. RESULTS: MA could dedifferentiate into fibroblast-shaped DA. After adipogenic differentiation, the inverted phase contrast microscope observation showed that there were much more lipid droplet in DA than in ADSCs. Absorption spectrometry assay of oil red O staining showed there were significant lipid droplet aggregation in DA 4 days of adipogenic induction. However, the same phenomenon could be observed in ADSCs at 10 days after differentiation. After 12 days, the absorption value of DA was higher than that of ADSCs, showing significant difference (P < 0.05). The cell counting of oil red O staining demonstrated that the adipogenic rates of DA and ADSCs were 65% +/- 6% and 35% -/+ 5%, respectively, showing significant difference (P < 0.05). CONCLUSION: The potential of adipogenic differentiation of DA is stronger than that of ADSCs. DA is a promising seed cell of adipose tissue engineering. PMID: 20632515 [PubMed - in process] | | |
| Culture of bone marrow mesenchymal stem cells on engineered matrix.
July 17, 2010 at 6:42 AM
|
| | Culture of bone marrow mesenchymal stem cells on engineered matrix. Methods Mol Biol. 2010;621:117-37 Authors: Park JS, Hashi C, Li S Mesenchymal stem cells (MSCs) have huge potential to be used in cell therapies because of their pluripotency and immunoregulatory attributes. To harness and maximize the therapeutic potential of MSCs, a thorough understanding of their differentiation pathways and their responses to the microenvironment is needed. The matrix that the cells reside on is an important microenvironmental cue, not only for its chemical components but also for its physical properties. The rigidity and topography of the matrix are two physical factors that are crucial in directing cell behavior. In this chapter, we describe the isolation, culture, and characterization of MSCs. Then we illustrate the procedure of creating different matrix rigidities using acrylamide gels for MSC differentiation study. Finally, we describe how to create MSC-seeded vascular grafts using scaffolds with nano topographical features. PMID: 20405363 [PubMed - indexed for MEDLINE] | | |
| Implantation of autogenous meniscal fragments wrapped with a fascia sheath enhances fibrocartilage regeneration in vivo in a large harvest site defect.
July 17, 2010 at 6:42 AM
|
| | Implantation of autogenous meniscal fragments wrapped with a fascia sheath enhances fibrocartilage regeneration in vivo in a large harvest site defect. Am J Sports Med. 2010 Apr;38(4):740-8 Authors: Kobayashi Y, Yasuda K, Kondo E, Katsura T, Tanabe Y, Kimura M, Tohyama H BACKGROUND: Concerning meniscal tissue regeneration, many investigators have studied the development of a tissue-engineered meniscus. However, the utility still remains unknown. HYPOTHESIS: Implantation of autogenous meniscal fragments wrapped with a fascia sheath into the donor site meniscal defect may significantly enhance fibrocartilage regeneration in vivo in the defect. STUDY DESIGN: Controlled laboratory study. METHODS: Seventy-five mature rabbits were used in this study. In each animal, an anterior one-third of the right medial meniscus was resected. Then, the animals were divided into the following 3 groups of 25 rabbits each: In group 1, no treatment was applied to the meniscal defect. In group 2, the defect was covered with a fascia sheath. In group 3, after the resected meniscus was fragmented into small pieces, the fragments were grafted into the defect. Then, the defect with the meniscal fragments was covered with a fascia sheath. In each group, 5 rabbits were used for histological evaluation at 3, 6, and 12 weeks after surgery, and 5 rabbits were used for biomechanical evaluation at 6 and 12 weeks after surgery. RESULTS: Histologically, large round cells in group 3 were scattered in the core portion of the meniscus-shaped tissue, and the matrix around these cells was positively stained by safranin O and toluisin blue at 12 weeks. The histological score of group 3 was significantly higher than that of group 1 and group 2. Biomechanically, the maximal load and stiffness of group 3 were significantly greater than those of groups 1 and 2. CONCLUSION: This study clearly demonstrated that implantation of autogenous meniscal fragments wrapped with a fascia sheath into the donor site meniscal defect significantly enhanced fibrocartilage regeneration in vivo in the defect at 12 weeks after implantation in the rabbit. CLINICAL RELEVANCE: This study proposed a novel strategy to treat a large defect after a meniscectomy. PMID: 20139330 [PubMed - indexed for MEDLINE] | | |
| Biomechanics of mandibular reconstruction: a review.
July 17, 2010 at 6:42 AM
|
| | Biomechanics of mandibular reconstruction: a review. Int J Oral Maxillofac Surg. 2010 Apr;39(4):313-9 Authors: Wong RC, Tideman H, Kin L, Merkx MA Knowledge of the biomechanics of the mandible allows the surgeon to understand the forces acting on the mandible during function and the resulting deformation that can occur. This allows the appropriate selection and placement of osteosynthesis plates to neutralize these forces. Many methods have been proposed for mandibular reconstruction, each of which has strengths and weaknesses. Most papers evaluating these techniques have focused on survival rates and the quality of the grafted bones, and there have been few studies of the biomechanics (stress distribution and strength) of the various types of reconstructed mandibles. This paper reviews the biomechanics of the mandible and the various methods of reconstruction reported in past studies. PMID: 19944568 [PubMed - indexed for MEDLINE] | | |
| Role of Cardiac Myocyte CXCR4 Expression in Development and Left Ventricular Remodeling After Acute Myocardial Infarction.
July 17, 2010 at 6:07 AM
|
| | Role of Cardiac Myocyte CXCR4 Expression in Development and Left Ventricular Remodeling After Acute Myocardial Infarction. Circ Res. 2010 Jul 15; Authors: Agarwal U, Ghalayini W, Dong F, Weber K, Zou YR, Rabbany SY, Rafii S, Penn MS Rationale: Stromal cell-derived factor (SDF)-1/CXCR4 axis has an instrumental role during cardiac development and has been shown to be a potential therapeutic target for optimizing ventricular remodeling after acute myocardial infarction (AMI) and in ischemic cardiomyopathy. Although a therapeutic target, the specific role of cardiac myocyte CXCR4 (CM-CXCR4) expression following cardiogenesis and survival of cardiac myocyte and left ventricular remodeling after AMI is unknown. Objective: We hypothesized that cardiac myocyte derived CXCR4 is critical for cardiac development, but it may have no role in adulthood secondary to the short transient expression of SDF-1 and the delayed expression of CM-CXCR4 following AMI. To address this issue, we developed congenital and conditional CM-CXCR4(-/-) mouse models. Methods and Results: Two strains of CM-CXCR4(flox/flox) mice were generated by crossing CXCR4(flox/flox) mice with MCM-Cre(+/-) mouse and MLC2v-Cre(+/-) mouse on the C57BL/6J background, yielding CXCR4(flox/flox) MCM-Cre(+/-) and CXCR4(flox/flox)MLC2v-Cre(+/-) mice. Studies demonstrated recombination in both models congenitally in the MLC2v-Cre(+/-) mice and following tamoxifen administration in the MCM-Cre(+/-) mice. Surprisingly the CXCR4(flox/flox)MLC2v-Cre(+/-) are viable, had normal cardiac function, and had no evidence of ventricular septal defect. CXCR4(flox/flox)MCM(+/-) treated with tamoxifen 2 weeks before AMI demonstrated 90% decrease in cardiac CXCR4 expression 48 hours after AMI. Twenty-one days post AMI, echocardiography revealed no statistically significant difference in the wall thickness, left ventricular dimensions or ejection fraction (40.9+/-7.5 versus 34.4+/-2.6%) in CXCR4(flox/flox) mice versus CM-CXCR4(-/-) mice regardless of strategy of Cre expression. No differences in vascular density (2369+/-131 versus 2471+/-126 vessels/mm(2); CXCR4(flox/flox) versus CM-CXCR4(-/-) mouse), infarct size, collagen content, or noninfarct zone cardiac myocyte size were observed 21 days after AMI. Conclusions: We conclude that cardiac myocyte-derived CXCR4 is not essential for cardiac development and, potentially because of the mismatch in timings of peaks of SDF-1 and CXCR4, has no major role in ventricular remodeling after AMI. PMID: 20634485 [PubMed - as supplied by publisher] | | |
| Hemocompatibility assessment of carbonic anhydrase modified hollow fiber membranes for artificial lungs.
July 17, 2010 at 6:07 AM
|
| | Hemocompatibility assessment of carbonic anhydrase modified hollow fiber membranes for artificial lungs. Artif Organs. 2010 May;34(5):439-42 Authors: Oh HI, Ye SH, Johnson CA, Woolley JR, Federspiel WJ, Wagner WR Hollow fiber membrane (HFM)-based artificial lungs can require a large blood-contacting membrane surface area to provide adequate gas exchange. However, such a large surface area presents significant challenges to hemocompatibility. One method to improve carbon dioxide (CO(2)) transfer efficiency might be to immobilize carbonic anhydrase (CA) onto the surface of conventional HFMs. By catalyzing the dehydration of bicarbonate in blood, CA has been shown to facilitate diffusion of CO(2) toward the fiber membranes. This study evaluated the impact of surface modifying a commercially available microporous HFM-based artificial lung on fiber blood biocompatibility. A commercial poly(propylene) Celgard HFM surface was coated with a siloxane, grafted with amine groups, and then attached with CA which has been shown to facilitate diffusion of CO(2) toward the fiber membranes. Results following acute ovine blood contact indicated no significant reduction in platelet deposition or activation with the siloxane coating or the siloxane coating with grafted amines relative to base HFMs. However, HFMs with attached CA showed a significant reduction in both platelet deposition and activation compared with all other fiber types. These findings, along with the improved CO(2) transfer observed in CA modified fibers, suggest that its incorporation into HFM design may potentiate the design of a smaller, more biocompatible HFM-based artificial lung. PMID: 20633159 [PubMed - in process] | | |
| Acknowledgements.
July 17, 2010 at 6:07 AM
|
| | Acknowledgements. Regen Med. 2010 Jul;5(4):679 Authors: PMID: 20632867 [PubMed - in process] | | |
| Container system for enabling commercial production of cryopreserved cell therapy products.
July 17, 2010 at 6:07 AM
|
| | Container system for enabling commercial production of cryopreserved cell therapy products. Regen Med. 2010 Jul;5(4):659-67 Authors: Woods EJ, Bagchi A, Goebel WS, Vilivalam VD, Vilivalam VD Aim: The expansion of cellular therapeutics will require large-scale manufacturing processes to expand and package cell products, which may not be feasible with current blood-banking bag technology. This study investigated the potential for freezing, storing and shipping cell therapy products using novel pharmaceutical-grade Crystal Zenith((R)) (CZ) plastic vials. Materials & methods: CZ vials (0.5, 5 and 30 ml volume) with several closure systems were filled with mesenchymal stem cells and stored at either -85 or -196 degrees C for 6 months. Vials were tested for their ability to maintain cell viability, proliferative and differentiation capacity, as well as durability and integrity utilizing a 1-m drop test. As controls, 2 ml polypropylene vials were investigated under the same conditions. Results: Post-thaw viability utilizing a dye exclusion assay was over 95% in all samples. Stored cells exhibited rapid recovery 2 h post-thaw and cultures were approximately 70% confluent within 5-7 days, consistent with nonfrozen controls and indicative of functional recovery. Doubling times were consistent over all vials. The doubling rate for cells from CZ vials were 2.14 +/- 0.83 days (1 week), 1.84 +/- 0.68 days (1 month) and 1.79 +/- 0.71 days (6 months), which were not significantly different compared with frozen and fresh controls. Cells recovered from the vials exhibited trilineage differentiation consistent with controls. As part of vial integrity via drop testing, no evidence of external damage was found on vial surfaces or on closure systems. Furthermore, the filled vials stored for 6 months were tested for container closure integrity. Vials removed from freezer conditions were transported to the test laboratory on dry ice and tested using pharmaceutical packaging tests, including dye ingress and microbial challenge. The results of all stoppered vials indicated container closure integrity with no failures. Conclusion: Pharmaceutical-grade plastic CZ vials, which are commercially used to package pharmaceutical products, are suitable for low-temperature storage and transport of mesenchymal stem cells, and are a scalable container system for commercial manufacturing and fill-finish operation of cell therapy products. PMID: 20632866 [PubMed - in process] | | |
| Heparin-releasing scaffold for stem cells: a differentiating device for vascular aims.
July 17, 2010 at 6:07 AM
|
| | Heparin-releasing scaffold for stem cells: a differentiating device for vascular aims. Regen Med. 2010 Jul;5(4):645-57 Authors: Spadaccio C, Rainer A, Centola M, Trombetta M, Chello M, Lusini M, Covino E, Toyoda Y, Genovese JA Aims: Current limitations of tissue-engineered vascular grafts include timing for the scaffold preparation, cell type, cell differentiation and growth inside the construct, and thrombogenicity of the final device. To surmount these shortcomings, we developed a heparin-releasing poly-L-lactide (PLLA) scaffold using the electrospinning technique, to guide the differentiation of human mesenchymal stem cells towards the endothelial phenotype and to deliver a useful drug in the management of the postimplantation period. Materials & methods: The heparin-releasing PLLA scaffold was produced by means of the electrospinning technique in a tubular shape. The scaffold was seeded with human mesenchymal stem cells and cultured for up to 1 week. Cell viability and cytotoxicity assays were performed, and cell differentiation was evaluated by immunofluorescence with confocal microscopy, cytofluorometry and western blotting. Heparin release was assayed by Azure A method and biological effectiveness of the drug was assessed by activated clotting time measurements. Results: The scaffold exhibited a morphology favorable to cell attachment. Heparin release showed an initial burst within the first 24 h, followed by a further sustained release profile. After 48 h of culturing, the construct demonstrated adequate engraftment and viability. Increased proliferation compared with the control scaffold in bare PLLA, suggested the induction of a favorable microenvironment. A shift towards CD31 positivity and modifications in cell morphology were observed in the heparin-releasing PLLA scaffold. Conclusion: By exploiting the biological effects of heparin, we developed an ad hoc differentiating device towards the endothelial phenotype for autologous stem cell seeding and, at the same time, we were able to facilitate and optimize the management of the construct once in clinical settings. PMID: 20632865 [PubMed - in process] | | |
| Effects of major human antiprotease alpha-1-antitrypsin on the motility and proliferation of stromal cells from human exfoliated deciduous teeth.
July 17, 2010 at 6:07 AM
|
| | Effects of major human antiprotease alpha-1-antitrypsin on the motility and proliferation of stromal cells from human exfoliated deciduous teeth. Regen Med. 2010 Jul;5(4):633-43 Authors: Aldonyte R, Tunaitis V, Surovas A, Suriakaite K, Jarmalaviciute A, Magnusson KE, Pivoriunas A Aim: Intrinsic tissue regeneration mechanisms are still not fully understood. The destruction/reconstruction processes are usually in fine balance; however, this can be easily destroyed, for example in the environment of chronic inflammation. One of the major proteins present at the inflammatory sites is the multifunctional protein alpha-1-antitrypsin (AAT). In this study, potential therapeutic effects of this major human antiprotease on progenitor cells are assessed. Materials & methods: Stromal cells from human exfoliated deciduous teeth (SHEDs) were used, which are similar to the mesenchymal stromal cells isolated from other tissues. SHEDs were cultivated in the presence of subphysiological, physiological and inflammatory concentrations of AAT, and their proliferation and motility traits were assayed. Some intracellular signaling pathways, AAT internalization by SHEDs and their matrix metalloprotease profile were studied in parallel. Results: Physiologic and inflammatory concentrations of AAT significantly increased the cell proliferation rate, induced phosphorylation of several key protein kinases and increased the amount of secreted active gelatinases. Moreover, cells exposed to physiologic and inflammatory levels of AAT were able to invade and migrate more efficiently. Subphysiologic AAT levels did not change cell behavior significantly. Conclusion: AAT at physiologic and inflammatory concentrations positively modulates the proliferation and motility of SHEDs in vitro. These results suggest the importance of AAT in the maintenance and regulation of tissue progenitor cells in vivo. PMID: 20632864 [PubMed - in process] | | |
| Commercialization challenges associated with induced pluripotent stem cell-based products.
July 17, 2010 at 6:07 AM
|
| | Commercialization challenges associated with induced pluripotent stem cell-based products. Regen Med. 2010 Jul;5(4):593-603 Authors: Smith D Induced pluripotent stem (iPS) cells have generated excitement in the regenerative medicine industry. Products derived from iPS cells could be used in a range of drug discovery and development processes. These nontherapeutic products will continue to be launched over the next 5 years, and provide income and knowledge to drive the therapeutic use of iPS cells forward. While the commercial opportunity for iPS cell-based therapies is potentially large, the looming technical and scientific hurdles must be overcome and, thus, the launch of a therapy based on iPS cells is unlikely to occur until the 2020s. While the launch of a therapeutic is many years away, the business models for commercialization should be well understood and proven based on experience with other non-iPS cell-based therapies (both autologous and allogeneic) that will already be on the market. PMID: 20632862 [PubMed - in process] | | |
| Human induced pluripotent stem cells: a review of the US patent landscape.
July 17, 2010 at 6:07 AM
|
| | Human induced pluripotent stem cells: a review of the US patent landscape. Regen Med. 2010 Jul;5(4):581-91 Authors: Georgieva BP, Love JM Human induced pluripotent stem (iPS) cells and human embryonic stem cells are cells that have the ability to differentiate into a variety of cell types. Embryonic stem cells are derived from human embryos; however, by contrast, human iPS cells can be obtained from somatic cells that have undergone a process of 'reprogramming' via genetic manipulation such that they develop pluripotency. Since iPS cells are not derived from human embryos, they are a less complicated source of human pluripotent cells and are considered valuable research tools and potentially useful in therapeutic applications in regenerative medicine. Worldwide, there are only three issued patents concerning iPS cells. Therefore, the patent landscape in this field is largely undefined. This article provides an overview of the issued patents as well as the pending published patent applications in the field. PMID: 20632861 [PubMed - in process] | | |
| Regulatory considerations for the development of autologous induced pluripotent stem cell therapies.
July 17, 2010 at 6:07 AM
|
| | Regulatory considerations for the development of autologous induced pluripotent stem cell therapies. Regen Med. 2010 Jul;5(4):569-79 Authors: Carpenter MK, Couture LA Induced pluripotent stem (iPS) cells offer tremendous opportunity for the creation of autologous cellular therapies, in which gene correction or the avoidance of immune response issues are desirable. In addition, iPS cells avoid the ethical concerns raised by the sourcing of human embryonic stem cells (hESCs) from embryos. iPS cells share many characteristics with hESCs and it is anticipated that existing experience with hESCs will translate to rapid progress in moving iPS cell-derived products toward clinical trials. While the potential clinical value for these products is considerable, the nature of current manufacturing paradigms for autologous iPS cell products raises considerable regulatory concerns. Here, the regulatory challenges posed by autologous iPS cell-derived products are examined. We conclude that there will be considerable regulatory concerns primarily relating to reproducibility of the manufacturing process and safety testing within clinically limited time constraints. Demonstrating safety of the final cell product in an autologous setting will be the single greatest obstacle to progressing autologous iPS cell-based therapies into the clinic. PMID: 20632860 [PubMed - in process] | | |
| Induced pluripotent stem cells: opportunities as research and development tools in 21st century drug discovery.
July 17, 2010 at 6:07 AM
|
| | Induced pluripotent stem cells: opportunities as research and development tools in 21st century drug discovery. Regen Med. 2010 Jul;5(4):557-68 Authors: Rowntree RK, McNeish JD Pluripotent embryonic stem cells (ESCs), when compared with transformed, primary or engineered cells, have unique characteristics and advantages that have resulted in the development of important cell-based tools in modern drug discovery. However, a key limitation has been the availability of human ESCs from patients with specific medical needs and the broad range of genetic variation represented worldwide. Induced pluripotent stem (iPS) cells are derived from somatic cells that are reprogrammed to a pluripotent stem cell state and have functional characteristics similar to ESCs. The demonstration that human iPS cells can be derived, with relative ease, through the introduction of transcription factor combinations has allowed the generation of disease-specific iPS cell lines. Therefore, iPS cell technology may deliver robust, human pluripotent cell lines from a wide range of clinical phenotypes and genotypes. Although human iPS cell technology is still a new tool in drug discovery, the promise that this technology will impact the discovery of new therapies can be projected based on the uptake of stem cell applications in biopharmaceutical sciences. Here, the near-term opportunities that iPS cells may deliver to drug discoverers to generate and test hypotheses will be discussed, with a focus on the specific strengths and weaknesses of iPS cell technology. Finally, the future perspective will address novel opportunities iPS cells could uniquely deliver to the preclinical development of new drug therapies. PMID: 20632859 [PubMed - in process] | | |
| miRNA in pluripotent stem cells.
July 17, 2010 at 6:07 AM
|
| | miRNA in pluripotent stem cells. Regen Med. 2010 Jul;5(4):545-55 Authors: Lakshmipathy U, Davila J, Hart RP Embryonic stem cells and induced pluripotent stem cells are characterized by their ability to self-renew and differentiate into any cell type. The molecular mechanism behind this process is a complex interplay between the transcriptional factors with epigenetic regulators and signaling pathways. miRNAs are an integral part of this regulatory network, with essential roles in pluripotent maintenance, proliferation and differentiation. miRNAs are a class of small noncoding RNAs that target protein-encoding mRNA to inhibit translation and protein synthesis. Discovered close to 20 years ago, miRNAs have rapidly emerged as key regulatory molecules in several critical cellular processes across species. Recent studies have begun to clarify the specific role of miRNA in regulatory circuitries that control self-renewal and pluripotency of both embryonic stem cells and induced pluripotent stem cells. These advances suggest a critical role for miRNAs in the process of reprogramming somatic cells to pluripotent cells. PMID: 20632858 [PubMed - in process] | | |
| DNA methylation in cell differentiation and reprogramming: an emerging systematic view.
July 17, 2010 at 6:07 AM
|
| | DNA methylation in cell differentiation and reprogramming: an emerging systematic view. Regen Med. 2010 Jul;5(4):531-44 Authors: Huang K, Fan G Embryonic stem cells have the unique ability to indefinitely self-renew and differentiate into any cell type found in the adult body. Differentiated cells can, in turn, be reprogrammed to embryonic stem-like induced pluripotent stem cells, providing exciting opportunities for achieving patient-specific stem cell therapy while circumventing immunological obstacles and ethical controversies. Since both differentiation and reprogramming are governed by major changes in the epigenome, current directions in the field aim to uncover the epigenetic signals that give pluripotent cells their unique properties. DNA methylation is one of the major epigenetic factors that regulates gene expression in mammals and is essential for establishing cellular identity. Recent analyses of pluripotent and somatic cell methylomes have provided important insights into the extensive role of DNA methylation during cell-fate commitment and reprogramming. In this article, the recent progress of differentiation and reprogramming research illuminated by high-throughput studies is discussed in the context of DNA methylation. PMID: 20632857 [PubMed - in process] | | |
| Potential of human induced pluripotent stem cells derived from blood and other postnatal cell types.
July 17, 2010 at 6:07 AM
|
| | Potential of human induced pluripotent stem cells derived from blood and other postnatal cell types. Regen Med. 2010 Jul;5(4):521-30 Authors: Ye Z, Cheng L Human induced pluripotent stem (iPS) cells have been generated from various cell types including blood cells, and offer certain advantages as a starting population for reprogramming postnatal somatic cells. Unlike adult stem cells, iPS cells can proliferate limitlessly in culture while retaining their potential to differentiate into any cell type, including hematopoietic lineages. Derivation of patient-specific iPS cells, in combination with improved hematopoietic differentiation protocols, provides an alternative to generate histocompatible stem cells for bone marrow transplantation. In addition, the ability to reprogram blood cells and redifferentiate iPS cells back to hematopoietic lineages provides opportunities to establish novel models for acquired and inherited blood diseases. This article will summarize recent progress in human iPS cells derived from blood cells and hematopoietic differentiation from iPS cells. Advantages of blood as a source for reprogramming and applications in regenerative medicine will be discussed. PMID: 20632856 [PubMed - in process] | | |
| Translational prospects for human induced pluripotent stem cells.
July 17, 2010 at 6:07 AM
|
| | Translational prospects for human induced pluripotent stem cells. Regen Med. 2010 Jul;5(4):509-19 Authors: Csete M The pace of research on human induced pluripotent stem (iPS) cells is frantic worldwide, based on the enormous therapeutic potential of patient-specific pluripotent cells free of the ethical and political issues that plagued human embryonic stem cell research. iPS cells are now relatively easy to isolate from somatic cells and reprogramming can be accomplished using nonmutagenic technologies. Access to iPS cells is already paying dividends in the form of new disease-in-a-dish models for drug discovery and as scalable sources of cells for toxicology. For translation of cell therapies, the major advantage of iPS cells is that they are autologous, but for many reasons, perfect immunologic tolerance of iPS-based grafts should not be assumed. This article focuses on the functional identity of iPS cells, anticipated safety and technical issues in their application, as well as a survey of the progress likely to be realized in clinical applications in the next decade. PMID: 20632855 [PubMed - in process] | | |
| Interview: Disease in a dish: a new approach to drug discovery.
July 17, 2010 at 6:07 AM
|
| | Interview: Disease in a dish: a new approach to drug discovery. Regen Med. 2010 Jul;5(4):505-7 Authors: Walker J John Walker currently serves as the CEO of iPierian, Inc., a private company focused on the creation of new therapeutics discovered using cellular reprogramming and directed differentiation of patient cells. Previously he has served as the Chairman and CEO of Novacea, Inc., Axys Pharmaceuticals, and its predecessor Arris Pharmaceuticals, Bayhill Therapeutics and Vitaphore Corporation. In addition, he was Chairman and interim CEO of KAI Pharmaceuticals, Centaur Pharmaceuticals and Guava Technologies, and was Chairman of the Board of Signal Pharmaceuticals, Renovis, Inc., Microcide, Inc., Intramed Corporation and BidShift Inc. He started his career at American Hospital Supply Corporation where he eventually served as President of the Hospital Company. J Walker currently serves on the Board of Directors of Affymax, Inc., Evotec and Transcept, Inc. He holds a BA from the State University of New York at Buffalo and is a graduate of the Advanced Executive Program, JL Kellogg Graduate School of Management at Northwestern University. PMID: 20632854 [PubMed - in process] | | |
| Research highlights.
July 17, 2010 at 6:07 AM
|
| | Research highlights. Regen Med. 2010 Jul;5(4):501-3 Authors: Gaines P, Liu R, Park IH PMID: 20632853 [PubMed - in process] | | | | 
| This email was sent to regenmd@gmail.com. Account Login
Don't want to receive this feed any longer? Unsubscribe here
This email was carefully delivered by Feed My Inbox. 230 Franklin Road Suite 814 Franklin, TN 37064 | |
No comments:
Post a Comment