|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | Directors of the California stem cell agency, in sharply divided moves, today said that its next chairman should serve in a part-time capacity in largely an oversight role.
The board's actions are aimed at giving guidance to four elected state officials who have the authority to nominate persons for the job, which carries a salary that can reach as high as $500,000 for fulltime work. The moves | | | | | | | | | | | | | | | | | | | | | | | | | CIRM directors have concluded their meeting. We will have a story coming up shortly on action dealing with the selection of a new chair. | | | | | | | | | | | | | | | | | | | | | | | | | The governing board of the California stem cell agency has resumed its session with a discussion of the selection of a new chair. | | | | | | | | | | | | | | | | | | | | | | | | A $600,000 venture into scientific publishing with a North Carolina firm today received the go-ahead from the governing board of the California stem cell agency.
Anthony Atala
The endeavor with AlphaMed Press of Durham, N.C., is expected to focus on translational aspects of stem cell research. The research journal would operate independently of CIRM and have a $1 million annual budget. CIRM | | | | | | | | | | | | | | | | | | | | | | | | | The governing board of the California stem cell agency is on a lunch break/executive session. Still to come today is action on the selection process for a person to replace Robert Klein as chairman of the enterprise. | | | | | | | | | | | | | | | | | | | | | | | | A UCLA stem cell researcher today won approval of an $1.8 million grant when directors of the California stem cell agency overturned an initial, negative decision by grant reviewers.
The proposal by Martin G. Martin deals with inherited diarrheal disorders. In January, Martin appealed the rejection by reviewers, and the board sent the proposal back to the grant panel. CIRM staff reported that | | | | | | | | | | | | | | | | | | | | | | | | The California stem cell agency board today approved $125,000 to send as many 125 persons to the World Stem Cell Summit in Pasadena in October.
Up to 75 would be patient advocates, a group that will be key in drumming up support for a new $3 billion to $5 billion bond ballot measure that has been proposed by by CIRM Chairman Robert Klein. The other 50 would be researchers and others involved in | | | | | | | | | | | | | | | | | | | | | | | | The California stem cell agency today approved on a voice vote a 32 percent increase($160,000) in fees this year for Remcho, Johansen & Purcell of San Leandro, Ca., for its work as outside counsel for the agency. Also approved was a $545,000 contract for 2011-12.
The firm, principally through James Harrison, has represented CIRM since 2004. Harrison is one of the five attorneys who drafted the | | | | | | | | | | | | | | | | | | | | | | | | Directors of the California stem cell agency today approved a $22 million extension of the $50 million shared lab program that was scheduled to expire in 2012.
CIRM said the programs at 17 research institutions are a "valuable resource." A CIRM memo declared,
"These labs provide dedicated (safe harbor) research space, specialized instrumentation, a supply of cell lines and culture materials, | | | | | | | | | | | | | | | | | | | | | | | | | Facile Synthesis and Characterization of Disulfide-Cross-Linked Hyaluronic Acid Hydrogels for Protein Delivery and Cell Encapsulation. Biomacromolecules. 2011 Mar 8; Authors: Choh SY, Cross D, Wang C Injectable hyaluronic acid (HA) hydrogels cross-linked via disulfide bond are synthesized using a thiol-disulfide exchange reaction. The production of small-molecule reaction product, pyridine-2-thione, allows the hydrogel formation process to be monitored quantitatively in real-time by UV spectroscopy. Rheological tests show that the hydrogels formed within minutes at 37 °C. Mechanical properties and equilibrium swelling degree of the hydrogels can be controlled by varying the ratio of HA pyridyl disulfide and macro-cross-linker PEG-dithiol. Degradation of the hydrogels was achieved both enzymatically and chemically by disulfide reduction with distinctly different kinetics and profiles. In the presence of hyaluronidase, hydrogel mass loss over time was linear and the degradation was faster at higher enzyme concentrations, suggesting surface-limited degradation. The kinetics of hydrogel erosion by glutathione was not linear, nor did the erosion rate correlate linearly with glutathione concentration, suggesting a bulk erosion mechanism. A cysteine-containing chemokine, stromal cell-derived factor 1α, was successfully encapsulated in the hydrogel and released in vitro without chemical alteration. Several different cell types, including fibroblasts, endothelial cells, and mesenchymal stem cells, were successfully encapsulated in the hydrogels with high cell viability during and after the encapsulation process. Substantial cell viability in the hydrogels was maintained up to 7 days in culture despite the lack of adhesion between the HA matrix and the cells. The facile synthesis of disulfide-cross-linked, dual-responsive degradable HA hydrogels may enable further development of bioactive matrices potentially suitable for tissue engineering and drug delivery applications. PMID: 21384907 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Engineering Bi-layer Nanofibrous Conduits for Peripheral Nerve Regeneration. Tissue Eng Part C Methods. 2011 Mar 8; Authors: Zhu Y, Wang A, Patel S, Kurpinski K, Diao E, Bao X, Kwong G, Young W, Li S Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam. In addition, the long-term effects of nanofibrous nerve conduits, in comparison with autografts, are still unknown. Here we developed a novel one-step electrospinning process, and for the first time, fabricated a seamless bi-layer nanofibrous nerve conduit: the luminal layer having longitudinally aligned nanofibers to promote nerve regeneration, and the outer layer having randomly organized nanofibers for mechanical support. Long-term in vivo studies demonstrated that bi-layer aligned nanofibrous nerve conduits were superior to random nanofibrous conduits and had comparable therapeutic effects to autografts for nerve regeneration. In summary, we showed that the engineered nanostructure had a significant impact on neural tissue regeneration in situ. The results from this study will also lead to the scalable fabrication of engineered nanofibrous nerve conduits with designed nanostructure. This technology platform can be combined with drug delivery and cell therapies for tissue engineering. PMID: 21385067 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | An improved kidney dissociation and re-aggregation culture system results in nephrons arranged organotypically around a single collecting duct system. Organogenesis. 2011 Apr 1;7(2) Authors: Ganeva V, Unbekandt M, Davies JA Methods for constructing engineered 'tissues' from simple suspensions of cells are valuable for investigations into basic developmental biology and for tissue engineering. We recently published a method for producing embryonic renal tissues from suspensions of embryonic mouse renal cells. This method reproduced the anatomies and differentiation states of nephrons and stroma very well; it had the limitation, however, that what would in normal development be a single, highly-branched collecting duct tree leading to a ureter developed, in the engineered system, as a multitude of very small collecting duct trees. These were isolated from each other and therefore would not be effective for draining urine to a common exit, were the tissue to be supplied with blood and physiologically active. Here, we report an improvement on the original method; it results in the formation of nephrons arranged around one single collecting duct tree as would happen in a normal kidney. PMID: 21386662 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | MR elastography monitoring of tissue-engineered constructs. NMR Biomed. 2011 Mar 8; Authors: Othman SF, Curtis ET, Plautz SA, Pannier AK, Butler SD, Xu H The objective of tissue engineering (TE) is to create functional replacements for various tissues; the mechanical properties of these engineered constructs are critical to their function. Several techniques have been developed for the measurement of the mechanical properties of tissues and organs; however, current methods are destructive. The field of TE will benefit immensely if biomechanical models developed by these techniques could be combined with existing imaging modalities to enable noninvasive, dynamic assessment of mechanical properties during tissue growth. Specifically, MR elastography (MRE), which is based on the synchronization of a mechanical actuator with a phase contrast imaging pulse sequence, has the capacity to measure tissue strain generated by sonic cyclic displacement. The captured displacement is presented in shear wave images from which the complex shear moduli can be extracted or simplified by a direct measure, termed the shear stiffness. MRE has been extended to the microscopic scale, combining clinical MRE with high-field magnets, stronger magnetic field gradients and smaller, more sensitive, radiofrequency coils, enabling the interrogation of smaller samples, such as tissue-engineered constructs. The following topics are presented in this article: (i) current mechanical measurement techniques and their limitations in TE; (ii) a description of the MRE system, MRE theory and how it can be applied for the measurement of mechanical properties of tissue-engineered constructs; (iii) a summary of in vitro MRE work for the monitoring of osteogenic and adipogenic tissues originating from human adult mesenchymal stem cells (MSCs); (iv) preliminary in vivo studies of MRE of tissues originating from mouse MSCs implanted subcutaneously in immunodeficient mice with an emphasis on in vivo MRE challenges; (v) future directions to resolve current issues with in vivo MRE in the context of how to improve the future role of MRE in TE. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21387443 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Honeycomb Self-Assembled Peptide Scaffolds by the Breath Figure Method. Chemistry. 2011 Mar 8; Authors: Du M, Zhu P, Yan X, Su Y, Song W, Li J The self-assembly of molecules into desired architectures is currently a challenging subject for the development of supramolecular chemistry. Here we present a facile "breath figure" assembly process through the use of the self-assembled peptide building block diphenylalanine (L-Phe-L-Phe, FF). Macroporous honeycomb scaffolds were fabricated, and average pore size could be regulated, from (1.00±0.18) μm to (2.12±0.47) μm, through the use of different air speeds. It is indicated that the honeycomb formation is humidity-, solvent-, concentration-, and substrate-dependent. Moreover, water molecules introduced from "breath figure" intervene in the formation of hydrogen bonds during FF molecular self-assembly, which results in a hydrogen bond configuration transition from antiparallel β sheet to parallel β sheet. Meanwhile, as a result of the higher polarity of water molecules, the FF molecular array is transformed from laminar stacking into a hexagonal structure. These findings not only elucidate the FF molecule self-assembly process, but also strongly support the mechanism of breath figure array formation. Finally, human embryo skin fibroblast (ESF) culture experiments suggest that FF honeycomb scaffolds are an attractive biomaterial for growth of adherent cells with great potential applications in tissue engineering. PMID: 21387428 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Aligned Hybrid Silk Scaffold for Enhanced Differentiation of Mesenchymal Stem Cells into Ligament Fibroblasts. Tissue Eng Part C Methods. 2011 Mar 8; Authors: Teh TK, Toh SL, Goh JC The concept of contact guidance utilizes the phenomenon of anchorage dependence of cells on the topography of seeded surfaces. It has been shown in previous studies that cells were guided to align along the topographical alignment of the seeding substrate and produced enhanced amounts of oriented extracellular matrix (ECM). In this study, we aimed to apply this concept to a three-dimensional full silk fibroin (SF) hybrid scaffold system, which comprised of knitted SF and aligned SF electrospun fibers (SFEFs), for ligament tissue engineering applications. Specifically, knitted SF, which contributed to the mechanical robustness of the system, was integrated with highly aligned SFEF (AL-SFEF) mesh, which acted as the initial ECM to provide environmental cues for positive cellular response. Mesenchymal stem cells (MSCs) seeded on the aligned hybrid scaffolds were shown to be proliferative and aligned along the integrated AL-SFEF, forming oriented spindle-shaped morphology and produced an aligned ECM network. Expression and production of ligament-related proteins were also increased as compared to hybrid SF scaffolds with randomly arranged SFEFs (RD-SFEF), indicating differentiative cues for ligament fibroblasts present in the aligned hybrid SF scaffolds. Consequently, the tensile properties of cultured aligned constructs were significantly improved and superior to the counterpart with RD-SFEF. These results thus showed that the aligned hybrid scaffold system was promising for enhancing cell proliferation, differentiation and function for ligament tissue engineering applications. PMID: 21385018 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Silicon, silica and its surface patterning/activation with alkoxy- and amino-silanes for nanomedical applications. Nanomedicine (Lond). 2011 Feb;6(2):281-300 Authors: Rother D, Sen T, East D, Bruce IJ Silica and silicates are widely used in nanomedicine with applications as diverse as medical device coatings to replacement materials in tissue engineering. Although much is known about silica and its synthesis, relatively few biomedical scientists fully appreciate the link that exists between its formulation and its resultant structure and function. This article attempts to provide insight into relevant issues in that context, as well as highlighting their importance in the material's eventual surface patterning/activation with alkoxy- and organo-silanes. The use of aminosilanes in that context is discussed at some length to permit an understanding of the specific variables that are important in the reproducible and robust aminoactivation of surfaces using such molecules. Recent investigative work is cited to underline the fact that although aminosilanization is a historically accepted mechanism for surface activation, there is still much to be explained about how and why the process works in the way it does. In the last section of this article, there is a detailed discussion of two classical approaches for the use of aminosilanized materials in the covalent immobilization of bioligands, amino-aldehyde and amino-carboxyl coupling. In the former case, the use of the homobifunctional coupler glutaraldehyde is explored, and in the latter, carbodiimides. Although these chemistries have long been employed in bioconjugations, it is apparent that there are still variables to be explored in the processes (as witnessed by continuing investigations into the chemistries concerned). Aspects regarding optimization, standardization and reproducibility of the fabrication of amino functionalized surfaces are discussed in detail and illustrated with practical examples to aid the reader in their own studies, in terms of considerations to be taken into account when producing such materials. Finally, the article attempts to remind readers that although the chemistry and materials involved are 'old hat', there is still much to be learnt about the methods involved. The article also reminds readers that although many highly specific and costly conjugation chemistries now exist for bioligands, there still remains a place for these relatively simple and cost-effective approaches in bioligand conjugate fabrication. PMID: 21385130 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Biotechnology in the Treatment of Sensorineural Hearing Loss: Foundations and Future of Hair Cell Regeneration. J Speech Lang Hear Res. 2011 Mar 8; Authors: Parker MA PURPOSE: To provide an overview of the methodologies involved in the field of hair cell regeneration. First, a tutorial on the biotechnological foundations of this field will be provided in order to assist the reader in the comprehension and interpretation of the research involved in hair cell regeneration. Next, a review of stem cell and gene therapy will be presented and a critical appraisal of their application to hair cell regeneration will be provided. The methodologies used in these approaches will be highlighted. METHOD: Narrative review of the fields of cellular, molecular, and developmental biology, tissue engineering, and stem cell and gene therapy using the PubMed database. RESULTS: The use of biotechnological approaches to the treatment of hearing loss, such as stem cell and gene therapy, has led to new methods of regenerating cochlear hair cells in mammals. CONCLUSIONS: There have been incredible strides made in assembling important pieces of the puzzle that comprise hair cell regeneration. However, mammalian hair cell regeneration using stem cell and gene therapy are years if not decades away from being clinically feasible. If the goals of the biological approaches are met, these therapies may represent the future treatments for hearing loss. PMID: 21386039 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Chitosan Scaffolds Containing Hyaluronic Acid for Cartilage Tissue Engineering. Tissue Eng Part C Methods. 2011 Mar 8; Authors: Correia C, Moreirateixeira LS, Moroni L, Reis RL, van Blitterswijk C, Karperien M, Mano J Scaffolds derived from natural polysaccharides are very promising in tissue engineering applications and regenerative medicine, as they resemble glycosaminoglycans in the extracellular matrix. In this study we have prepared freeze-dried composite scaffolds of chitosan (CHT) and hyaluronic acid (HA), in different weight ratios containing either no HA (control), 1%, 5%, or 10% of HA. We hypothesized that HA could enhance structural and biological properties of chitosan scaffolds. To test this hypothesis, physico-chemical and biological properties of CHT/HA scaffolds were evaluated. SEM micrographs, mechanical properties, swelling tests, enzymatic degradation, and FT-IR chemical maps were performed. To test the ability of the CHT/HA scaffolds to support chondrocyte adhesion and proliferation, live-dead and MTT assays were performed. Results showed that CHT/HA composite scaffolds are non-cytotoxic and promote cell adhesion. ECM formation was further evaluated with safranin-O and alcian blue stainings, and GAG and DNA quantifications were performed. The incorporation of HA enhanced cartilage ECM production. CHT/5HA had a better pore network configuration and exhibited enhanced ECM cartilage formation. Based on our results we believe that CHT/HA composite matrixes have potential use in cartilage repair. PMID: 21385066 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Image-based tissue engineering of a total intervertebral disc implant for restoration of function to the rat lumbar spine. NMR Biomed. 2011 Mar 8; Authors: Bowles RD, Gebhard HH, Dyke JP, Ballon DJ, Tomasino A, Cunningham ME, Härtl R, Bonassar LJ Nonbiological total disc replacement is currently being used for the treatment of intervertebral disc (IVD) disease and injury, but these implants are prone to mechanical wear, tear and possible dislodgement. Recently, tissue-engineered total disc replacement (TE-TDR) has been investigated as a possible alternative to more fully replicate the native IVD properties. However, the performance of TE-TDRs has not been studied in the native disc space. In this study, MRI and microcomputed tomography imaging of the rat spine were used to design a collagen (annulus fibrosus)/alginate (nucleus pulposus) TE-TDR to a high degree of geometric accuracy, with less than 10% difference between TE-TDR and the native disc dimensions. Image-based TE-TDR implants were then inserted into the L4/L5 disc space of athymic rats (n = 5) and maintained for 16 weeks. The disc space was fully or partially maintained in three of five animals and proteoglycan and collagen histology staining was similar in composition to the native disc. In addition, good integration was observed between TE-TDR and the vertebral bodies, as well as remnant native IVD tissue. Overall, this study provides evidence that TE-TDR strategies may yield a clinically viable treatment for diseased or injured IVD. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21387440 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Roles of SATB2 in Osteogenic Differentiation and Bone Regeneration. Tissue Eng Part A. 2011 Mar 8; Authors: Zhang J, Tu Q, Grosschedl R, Kim MS, Griffin T, Drissi H, Yang P, Chen J Expressed in branchial arches and osteoblast-lineage cells, SATB2 is responsible for preventing craniofacial abnormalities and defects in osteoblast function. In this study, we transduced SATB2 into murine adult stem cells, and found that SATB2 significantly increased expression levels of bone matrix proteins, osteogenic transcription factors, and a potent angiogenic factor, VEGF. Using an Osx promoter-luciferase construct and calvarial cells isolated from Runx2-deficient mice, we found that SATB2 up-regulates Osx expression independent of Runx2, but synergistically enhances the regulatory effect of Runx2 on Osx promoter. We then transplanted SATB2-overexpressing adult stem cells genetically double-labeled with BSP promoter-driven luciferase and β-actin promoter-driven EGFP into mandibular bone defects. We identified increased luciferase-positive cells in SATB2-overexpressing groups, indicating more transplanted cells undergoing osteogenic differentiation. New bone formation was consequently accelerated in SATB2 groups. In conclusion, SATB2 acts as a potent transcription factor to enhance osteoblastogenesis and promote bone regeneration. The application of SATB2 in bone tissue engineering gives rise to a higher bone forming capacity as a result of multiple-level amplification of regulatory activity. PMID: 21385070 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Directors of the California stem cell agency have settled into their business session with action scheduled today on approval of a once-rejected $1.8 million grant by a UCLA researcher and a closed-door meeting on CIRM's first-ever involvement in clinical trials, a $50 million loan round for stem cell companies. Geron and Advanced Cell Technology are likely to be among the applicants. | | | | | | | | | | | | | | | | | | | | | | | | | Directors of the California stem cell agency have settled into their business session with action scheduled today on approval a once-rejected $1.8 million grant by a UCLA researcher and a closed-door meeting on CIRM's first-ever involvement in clinical trials, a $50 million loan round for stem cell companies. Geron and Advanced Cell Technology are likely to be among the applicants. | | | | | | | | | | | | | | | | | | | | | | | | The board of the $3 billion California stem cell agency should direct its chairman to step aside from management of the organization and concentrate on oversight, it was told this morning.
In remarks prepared for delivery at the directors' meeting in Burlingame, Ruth Holton-Hodson, a representative of California's top fiscal officer, said,
"Frankly, it is difficult to uphold the appearance of | | | | | | | | | | | | | | | | | | | | | | | | | The briefing on cardiovascular disease for directors of the California stem cell agency has concluded. The governing board is expected to convene shortly to deal with other matters, ranging from selection of a new chair to a $125,000 program to send patient advocates to the World Stem Cell Stem Summit in Pasadena. | | | | | | | | | | | | | | | | | | | | | | | | | The briefing on cardiovascular disease for directors of the California stem cell agency has concluded. The governing board is expected to convene shortly to deal with other matters, ranging from selection of a new chair to a $125,000 program to send patient advocates to the World Stem Cell Stem Summit in Pasadena. | | | | | | | | | | | | | | | | | | | | | | | | | Turning straw into gold: directing cell fate for regenerative medicine. Nat Rev Genet. 2011 Mar 9; Authors: Cohen DE, Melton D Regenerative medicine offers the hope that cells for disease research and therapy might be created from readily available sources. To fulfil this promise, the cells available need to be converted into the desired cell types. We review two main approaches to accomplishing this goal: in vitro directed differentiation, which is used to push pluripotent stem cells, including embryonic stem cells or induced pluripotent stem cells, through steps similar to those that occur during embryonic development; and reprogramming (also known as transdifferentiation), in which a differentiated cell is converted directly into the cell of interest without proceeding through a pluripotent intermediate. We analyse the status of progress made using these strategies and highlight challenges that must be overcome to achieve the goal of cell-replacement therapy. PMID: 21386864 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Eya1 controls cell polarity, spindle orientation, cell fate and Notch signaling in distal embryonic lung epithelium. Development. 2011 Apr;138(7):1395-407 Authors: El-Hashash AH, Turcatel G, Al Alam D, Buckley S, Tokumitsu H, Bellusci S, Warburton D Cell polarity, mitotic spindle orientation and asymmetric division play a crucial role in the self-renewal/differentiation of epithelial cells, yet little is known about these processes and the molecular programs that control them in embryonic lung distal epithelium. Herein, we provide the first evidence that embryonic lung distal epithelium is polarized with characteristic perpendicular cell divisions. Consistent with these findings, spindle orientation-regulatory proteins Insc, LGN (Gpsm2) and NuMA, and the cell fate determinant Numb are asymmetrically localized in embryonic lung distal epithelium. Interfering with the function of these proteins in vitro randomizes spindle orientation and changes cell fate. We further show that Eya1 protein regulates cell polarity, spindle orientation and the localization of Numb, which inhibits Notch signaling. Hence, Eya1 promotes both perpendicular division as well as Numb asymmetric segregation to one daughter in mitotic distal lung epithelium, probably by controlling aPKCζ phosphorylation. Thus, epithelial cell polarity and mitotic spindle orientation are defective after interfering with Eya1 function in vivo or in vitro. In addition, in Eya1(-/-) lungs, perpendicular division is not maintained and Numb is segregated to both daughter cells in mitotic epithelial cells, leading to inactivation of Notch signaling. As Notch signaling promotes progenitor cell identity at the expense of differentiated cell phenotypes, we test whether genetic activation of Notch could rescue the Eya1(-/-) lung phenotype, which is characterized by loss of epithelial progenitors, increased epithelial differentiation but reduced branching. Indeed, genetic activation of Notch partially rescues Eya1(-/-) lung epithelial defects. These findings uncover novel functions for Eya1 as a crucial regulator of the complex behavior of distal embryonic lung epithelium. PMID: 21385765 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Epigenetic and phenotypic profile of fibroblasts derived from induced pluripotent stem cells. PLoS One. 2011;6(2):e17128 Authors: Hewitt KJ, Shamis Y, Hayman RB, Margvelashvili M, Dong S, Carlson MW, Garlick JA Human induced pluripotent stem (hiPS) cells offer a novel source of patient-specific cells for regenerative medicine. However, the biological potential of iPS-derived cells and their similarities to cells differentiated from human embryonic stem (hES) cells remain unclear. We derived fibroblast-like cells from two hiPS cell lines and show that their phenotypic properties and patterns of DNA methylation were similar to that of mature fibroblasts and to fibroblasts derived from hES cells. iPS-derived fibroblasts (iPDK) and their hES-derived counterparts (EDK) showed similar cell morphology throughout differentiation, and patterns of gene expression and cell surface markers were characteristic of mature fibroblasts. Array-based methylation analysis was performed for EDK, iPDK and their parental hES and iPS cell lines, and hierarchical clustering revealed that EDK and iPDK had closely-related methylation profiles. DNA methylation analysis of promoter regions associated with extracellular matrix (ECM)-production (COL1A1) by iPS- and hESC-derived fibroblasts and fibroblast lineage commitment (PDGFRβ), revealed promoter demethylation linked to their expression, and patterns of transcription and methylation of genes related to the functional properties of mature stromal cells were seen in both hiPS- and hES-derived fibroblasts. iPDK cells also showed functional properties analogous to those of hES-derived and mature fibroblasts, as seen by their capacity to direct the morphogenesis of engineered human skin equivalents. Characterization of the functional behavior of ES- and iPS-derived fibroblasts in engineered 3D tissues demonstrates the utility of this tissue platform to predict the capacity of iPS-derived cells before their therapeutic application. PMID: 21386890 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A new allele of Lyl1 confirms its important role in hematopoietic stem cell function. Genesis. 2011 Mar 8; Authors: Souroullas GP, Goodell MA Lyl1 codes for a bHLH protein that is an important regulator of hematopoietic stem cell function. An existing mutant allele of Lyl1 features a lacZ gene inserted in-frame into the fourth exon, leaving behind the N-terminus and the DNA-binding basic region, resulting in a translated chimeric protein. Here, we have generated a null allele, which allowed us to examine residual function of the N-terminus in the absence of a bHLH region. The new Lyl1-/- mouse model exhibited a reduced ability to generate lymphoid lineages and a somewhat more severe hematopoietic repopulation defect when transplanting purified hematopoietic stem cells. Our data show that in the absence of the HLH but presence of the N-terminus, residual function of the Lyl1 is detectable but relatively minor. The new model may be of use for studies of Lyl1 in which a null allele is required, or for which presence of the LacZ may complicate the combined use of additional mouse models bearing the lacZ marker. © 2011 Wiley-Liss, Inc. PMID: 21387538 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | We plan to bring our readers live coverage of the meeting today of the board of the California stem cell agency, assuming our Internet connection from Nicaragua holds up. The board is expected to discuss the selection of a new chair and the agency's response to recommendations for closer ties to industry and aggressive outreach for promising research outside of California. Readers can listen to | | | | | | | | | | | | | | | | | | | | | | | | | Tissue regeneration in loss of substance on the lower limbs through use of platelet-rich plasma, stem cells from adipose tissue, and hyaluronic acid. Adv Skin Wound Care. 2010 Jun;23(6):262-72 Authors: Cervelli V, De Angelis B, Lucarini L, Spallone D, Balzani A, Palla L, Gentile P, Cerulli P Platelet-rich plasma (PRP) induces wound regeneration and tissue repair through cell proliferation and differentiation, promoting tissue healing and also acting as an autologous scaffold. With a small quantity of blood, it is possible to obtain the necessary optimal volume of PRP to treat the loss of substance in the lower limb. It has been demonstrated that mesenchymal stem cells are present in the adipose tissue (thus accelerating the effect of the PRP). PMID: 20489388 [PubMed - indexed for MEDLINE] | | | | | | | | | |  | |  | |  |
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