| |  | | | | | MAINTENANCE: Feed My Inbox will be undergoing maintenance on Saturday Feb 12th from 8-11am CST. Emails will be delayed during this period. More details | | | | | | | | | | | | |  | |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Bioconjugation of hydrogels for tissue engineering. Curr Opin Biotechnol. 2011 Feb 7; Authors: Jabbari E Success of tissue engineered constructs in regenerative medicine is limited by the lack of cellmatrix interactions to guide devleopment of the seeded cells into the desired tissue. This review highlights the most exciting developments in bioconjugation of synthetic hydrogels targeted to tissue engineering. Application of conjugation techniques has resulted in the synthesis of novel biomimetic cell-responsive hydrogels to control the cascade of cell migration, adhesion, survival, differentiation, and maturation to the desired lineage concurrent with matrix remodeling. The future outlook includes developing conjugated patterned hydrogel matrices, developing novel hydrogel matrices to support self-renewal and pluripotency of embryonic and adult stem cells, and merging 3D printing with bioconjugation to fabricate hydrogels with anatomical arrangement of cells and biomolecules. PMID: 21306888 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Micromechanical regulation in cardiac myocytes and fibroblasts: implications for tissue remodeling. Pflugers Arch. 2011 Feb 11; Authors: Curtis MW, Russell B Cells of the myocardium are at home in one of the most mechanically dynamic environments in the body. At the cellular level, pulsatile stimuli of chamber filling and emptying are experienced as cyclic strains (relative deformation) and stresses (force per unit area). The intrinsic characteristics of tension-generating myocytes and fibroblasts thus have a continuous mechanical interplay with their extrinsic surroundings. This review explores the ways that the micromechanics at the scale of single cardiac myocytes and fibroblasts have been measured, modeled, and recapitulated in vitro in the context of adaptation. Both types of cardiac cells respond to externally applied strain, and many of the intracellular mechanosensing pathways have been identified with the careful manipulation of experimental variables. In addition to strain, the extent of loading in myocytes and fibroblasts is also regulated by cues from the microenvironment such as substrate surface chemistry, stiffness, and topography. Combinations of these structural cues in three dimensions are needed to mimic the micromechanical complexity derived from the extracellular matrix of the developing, healthy, or pathophysiologic heart. An understanding of cardiac cell micromechanics can therefore inform the design and composition of tissue engineering scaffolds or stem cell niches for future applications in regenerative medicine. PMID: 21308471 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | ALDH Bright Stem and Progenitor Cell Populations from Normal Tissues: Characteristics, Activities and Emerging Uses in Regenerative Medicine. Stem Cells. 2011 Feb 4; Authors: Balber AE PMID: 21308868 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Intracranial hemangiopericytoma: Case study with cytogenetics and genome wide SNP-A analysis. Pathol Res Pract. 2011 Feb 7; Authors: Holland H, Livrea M, Ahnert P, Koschny R, Kirsten H, Meixensberger J, Bauer M, Schober R, Fritzsch D, Krupp W The tumor entity of hemangiopericytoma is not universally recognized as a nosological entity by pathologists, and there is a trend toward reassigning it to other categories gradually. However, hemangiopericytomas occurring in the nervous system are included in the new WHO classification of brain tumors, and are distinguished from both meningioma and fibrous tumors. Since there are few genetic studies, we performed a comprehensive cytogenetic analysis of an infratentorial hemangiopericytoma in a 55-year-old female. It was originally classified as a grade II tumor but recurred as a grade III tumor with a proliferation index of 20%. Using trypsin-Giemsa staining (GTG-banding) and multicolor fluorescence in situ hybridization (M-FISH), we could confirm the loss of chromosomal material 10q, which has been previously described in hemangiopericytoma, and we identified de novo chromosomal aberrations on chromosome 8. Applying genome-wide high-density single nucleotide polymorphism array (SNP-A) analysis, we detected segments with loss or gain, as well as clonal deletions or regions suggestive of segmental uniparental disomy. These findings, together with the results of conventional histological and immunohistochemical characterization, provide additional evidence for the nosological separation of hemangiopericytoma in the central nervous system as a biologically different entity. PMID: 21306833 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Silk fibroin microparticles as carriers for delivery of human recombinant bone morphogenetic protein-2: in vitro and in vivo bioactivity. Tissue Eng Part C Methods. 2010 Oct;16(5):937-45 Authors: Bessa PC, Balmayor ER, Hartinger J, Zanoni G, Dopler D, Meinl A, Banerjee A, Casal M, Redl H, Reis RL, van Griensven M The in vitro and in vivo efficiency of fibroin microparticles as a delivery carrier for bone morphogenetic protein-2 (BMP-2) was evaluated. BMP-2 was encapsulated in silk fibroin particles that were produced by a simple and very mild processing method. The dose-response of BMP-2-loaded fibroin particles was examined in C2C12 cells, after 5 days of culture. The BMP-2 retained most of its activity as observed by the increase in alkaline phosphatase activity, which was much higher when BMP-2 was encapsulated into the particles rather than just surface-adsorbed. After 2 weeks of culture, increased mineralization was observed with BMP-2-loaded particles in comparison to soluble added growth factor. No significant cytotoxicity was detected. When implanted in a rat ectopic model, bone formation was observed by in vivo micro-computed tomography after 2 and 4 weeks postimplantation, with particles loaded with 5 or 12.5 microg BMP-2. An increase in bone density was observed over time. Histology revealed further evidence of ectopic bone formation, observed by strong alizarin red staining and osteocalcin immunostaining. Our findings show that fibroin microparticles may present an interesting option for future clinical applications in the bone tissue engineering field, and therefore, further studies have been planned. PMID: 19958078 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | ASSEMBLY OF HELPER-DEPENDENT ADENOVIRUS DNA INTO CHROMATIN PROMOTES EFFICIENT GENE EXPRESSION. J Virol. 2011 Feb 9; Authors: Ross PJ, Kennedy MA, Christou C, Risco Quiroz M, Poulin KL, Parks RJ Helper-dependent adenovirus (hdAd) vectors have shown tremendous potential in numerous preclinical studies in animal models of human disease. Expression of a therapeutic transgene can be maintained for several years after a single administration of the hdAd vector. However, despite the long-term persistence of the hdAd DNA in the transduced cell, little is known of the fate and structure of hdAd DNA within the host nucleus. In this study, we have characterized the assembly of hdAd DNA into chromatin in tissue culture. Eviction of the Ad DNA-packaging protein VII, histone deposition, and vector-associated gene expression all began within 2-6 hours of host cell transduction. Inhibition of transcription elongation through the vector DNA template had no effect on the loss of VII, suggesting that transcription was not necessary for removal of the majority of protein VII. Vector DNA assembled into physiologically-spaced nucleosomes within 6 hours. hdAd vectors incorporated the histone H3 variant H3.3, which was dependent on the histone chaperone HIRA. Knockdown of HIRA reduced hdAd association with histones and reduced expression of the vector-encoded transgene by 2- to 3-fold. Our study elucidates an essential role for hdAd DNA chromatinization for optimal vector gene expression. PMID: 21307207 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Self Renewal vs. Lineage Commitment of Embryonic Stem Cells: Protein Kinase C Signaling Shifts the Balance. Stem Cells. 2011 Feb 3; Authors: Dutta D, Ray S, Home P, Larson M, Wolfe MW, Paul S The intricate molecular mechanisms that regulate embryonic stem (ES) cell pluripotency are incompletely understood. Prior research indicated that activation of JAK-STAT3 pathway or inhibition of ERK/GSK3 signaling maintains mouse ES cell (mESC) pluripotency. Here we demonstrate that inhibition of protein kinase C (PKC) isoforms maintains mESC pluripotency without the activation of STAT3 or inhibition of ERK/GSK3 signaling pathways. Our analyses revealed that the atypical PKC isoform, PKCζ plays an important role in inducing lineage commitment in mESCs through a PKCζ-NF-κB signaling axis and inhibition of PKC isoforms maintains ES cell-specific epigenetic modifications. Furthermore, inhibition of PKC isoforms permits derivation of germline-competent ES cells from mouse blastocysts and also facilitates reprogramming of mouse embryonic fibroblasts (MEFs) towards induced pluripotent stem cells (iPSCs). Our results indicate that PKC signaling is critical to balancing ES cell self-renewal and lineage commitment. PMID: 21308862 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Esophageal Preservation in Five Male Patients after Endoscopic Inner - Layer Circumferential Resection in the Setting of Superficial Cancer: A Regenerative Medicine Approach with a Biologic Scaffold. Tissue Eng Part A. 2011 Feb 10; Authors: Badylak SF, Hoppo T, Nieponice A, Gilbert TW, Davison JM, Jobe BA As a result of injury caused by chronic gastroesophageal reflux, Barrett's esophagus with high grade dysplasia and esophageal adenocarcinoma are rapidly increasing problems in the United States. The current standard of care involves esophagectomy; a procedure associated with a high morbidity, a negative impact on long term quality of life, and a mortality rate of 1-6 percent. An entirely endoscopic technique for circumferential, long segment en bloc removal of the mucosa and submucosa with subsequent placement of a biologic scaffold material that promotes a constructive remodeling response and minimizes stricture is described herein. The results of this approach are reported for five patients with four to twenty-four month follow up. Restoration of normal mature, K4+/K14+, squamous epithelium, and return to a normal diet without significant dysphagia is reported for all patients. Two of five patients show a small focus of recurrent Barrett's esophagus at the gastroesophageal junction but the entire length and circumference of the reconstituted esophageal mucosa remains free of disease. This experience provides evidence that a regenerative medicine approach may, for the first time, enable aggressive endoscopic resection of early stage neoplasia without the need for esophagectomy and its associated complications. PMID: 21306292 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | TGFβ-Mediated Sox10 Suppression Controls Mesenchymal Progenitor Generation in Neural Crest Stem Cells. Stem Cells. 2011 Feb 3; Authors: John N, Cinelli P, Wegner M, Sommer L During vertebrate development, neural crest stem cells (NCSCs) give rise to neural cells of the peripheral nervous system and to a variety of mesenchymal cell types, including smooth muscle, cranio-facial chondrocytes, and osteocytes. Consistently, mesenchymal stem cells (MSCs) have recently been shown to derive in part from the neural crest (NC), although, the mechanisms underlying MSC generation remains to be identified. Here we show that TGFβ-mediated suppression of the NCSC transcription factor Sox10 induces a switch in neural to mesenchymal potential in NCSCs. In vitro and in vivo, TGFβ signal inactivation results in persistent Sox10 expression, decreased cell cycle exit, and perturbed generation of mesenchymal derivatives, which eventually leads to defective morphogenesis. In contrast, TGFβ-mediated downregulation of Sox10 or its genetic inactivation suppresses neural potential, confers mesenchymal potential to neural crest cells in vitro, and promotes cell cycle exit and precocious mesenchymal differentiation in vivo. Thus, negative regulation of Sox10 by TGFβ signaling promotes the generation of mesenchymal progenitors from NCSCs. Our study might lay the grounds for future applications demanding defined populations of MSCs for regenerative medicine. PMID: 21308864 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A compact, automated cell culture system for clinical scale cell expansion from primary tissues. Tissue Eng Part C Methods. 2010 Oct;16(5):947-56 Authors: Kato R, Iejima D, Agata H, Asahina I, Okada K, Ueda M, Honda H, Kagami H Despite the growing number of clinically practical automated cell culture systems, demand is also increasing for more compact platforms with greater capabilities to prepare primary cells directly from patient tissue. Here we report the development of an automated cell culture system that is also compact. The machinery consisted of a supply unit, an incubation unit, and a collection unit, which fit within a 70 cm x 60 cm x 86 cm space. The compact size was enabled by our concept of using a single culture vessel from the primary culture steps to final cell harvest instead of scaling up with multiple culture vessels. Human fibroblasts and bone marrow stromal cells (BMSCs) were successfully cultured with this system over 19 days without contamination. From three pieces of gingival tissue (2 mm x 2 mm) or from 10 mL of bone marrow aspirate, the system could produce more than 2.0x10(7) cells and up to 3.0x10(7) cells for fibroblasts and BMSCs, respectively. The BMSCs produced by this system were capable of ectopic bone formation after transplantation into the subcutaneous space of nude mice. Our prototype system will provide a foundation for minimizing automatic culture machinery with clinically relevant cell yields while also expanding the automation capabilities to include primary tissue culture. PMID: 19958165 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Synthesis and Characterization of Tunable PEG - Gelatin Methacrylate Composite Hydrogels. Tissue Eng Part A. 2011 Feb 10; Authors: Hutson CB, Nichol JW, Aubin H, Bae H, Yamanlar S, Al-Haque S, Koshy S, Khademhosseini A Poly(ethylene glycol) (PEG) hydrogels are popular for cell culture and tissue engineered applications because they are non-toxic and exhibit favorable hydration and nutrient transport. However, cells cannot adhere to, remodel, proliferate within or degrade PEG hydrogels. Methacrylated gelatin (GelMA), derived from denatured collagen, yields an enzymatically degradable, photocrosslinkable hydrogel that cells can adhere to and spread within. To combine the desirable features of each of these materials we synthesized PEG-GelMA composite hydrogels, hypothesizing that co-polymerization would enable adjustable cell binding, mechanical and degradation properties. The addition of GelMA resulted in a composite hydrogel that exhibited tunable mechanical and biological profiles. Adding GelMA (5-15% w/v) to PEG (5% and 10% w/v) proportionally increased fibroblast surface binding and spreading as high as 10 fold compared to PEG hydrogels (p<0.05). Encapsulated fibroblasts were also able to form 3D cellular networks 7 days following photoencapsulation only within composite hydrogels as compared to PEG alone. Additionally, PEG-GelMA hydrogels displayed tunable enzymatic degradation and stiffness profiles. The addition of GelMA increased the compressive modulus of 10% PEG hydrogesl from 0.018 MPa to 0.085 MPa. Whereas, the addition of PEG (10% w/v) to GelMA (5-10% w/v) reduced enzymatic degradation of composite hydrogels by more than 50%. PEG-GelMA composite hydrogels show great promise as tunable, cell-responsive hydrogels for 3D cell culture and regenerative medicine applications. PMID: 21306293 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The role of shear stress on mechanically stimulated engineered vascular substitutes: influence on mechanical and biological properties. J Tissue Eng Regen Med. 2011 Feb 8; Authors: Boccafoschi F, Bosetti M, Diego Mantovani CM, Cannas M Vascular tissue engineering represents a promising field in the replacement of diseased vessels. The biological properties of three-dimensional (3D) collagen scaffolds indicate this material as a valid choice for vascular tissue engineering. Unfortunately, mechanical properties still remain unsatisfactory, due to a low burst pressure resistance and a plastic deformation. The use of a bioreactor to apply appropriate mechanical stresses have already shown a remodelling effect on the extracellular matrix and the behaviour of cells. In this study, we have shown the effect of the mechanical stress on elastin synthesis, which has a direct effect on the mechanical properties of the tissue-engineered vessel. We measured and compared the stress-strain curves, the elastic modulus and tenacity of a collagen tubular scaffold in the presence of C2C12 murine myoblasts cells, before and after the maturation in the bioreactor, applying a shear stress of 5 dynes/cm(2) for 3 days. Interesting evidence concerning the extracellular matrix structure, which significantly modify the biomechanical characteristics of the cellular scaffold, were observed, underlying the importance of focusing more effort in the research field of physiologically-guided 3D tissue-engineered substitutes. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21308992 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue-engineered airway and "in situ tissue engineering". Gen Thorac Cardiovasc Surg. 2011 Feb;59(2):91-7 Authors: Nakamura T, Ohmori K, Kanemaru S Since the 1980s, tissue engineering has become one of the major areas of endeavor in medical research, applying the principles of biology and engineering to the development of functional substitutes for damaged tissue. Using this technology, various attempts have been made to create and apply a tissue-engineered prosthetic trachea, or airway. In addition to the conventional tissue engineering approach, a new substantially different concept has been advocated in Japan since 2000. This is "in situ tissue engineering," where a tissue is created not in vitro but in vivo, exploiting the potential of the living body for wound healing. An artificial trachea created by in situ tissue engineering has already been applied in human patients for reconstruction of airway defects, and promising results have been obtained. This article reviews recent progress in the relatively new field of airway reconstruction employing tissue engineering. PMID: 21308434 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Retinol (vitamin A) maintains self-renewal of pluripotent male germline stem cells (mGSCs) from adult mouse testis. J Cell Biochem. 2011 Feb 1; Authors: Zhang S, Sun J, Pan S, Zhu H, Wang L, Hu Y, Wang J, Wang F, Cao H, Yan X, Hua J Studies have shown that male germline stem cells (mGSCs), which are responsible for maintaining spermatogenesis in the male, could be obtained from mouse and human testis. However, the traditional cultural methods were mostly dependent on serum and feeder, and the initial mGSCs were either obtained from neonatal mice or the detailed description of its potency and origin was not provided. Here we reported a novel (retinol (RE) serum-free and feeder-free) system for the successful culture of adult germline stem cells from adult Kunming mice (8-24 weeks) testis. The isolated mGSCs cultured in RE serum-free and feeder-free medium maintained the typical morphology of undifferentiated embryonic stem cells (ESCs), and they proliferated well in RE medium analysed by proliferation assay, RT-PCR, microarray and western blotting. These cells also showed typical properties of ESCs (alkaline phosphatase (AP) positive, expressions of Oct4, Sox2, Nanog and SSEA1, with the capacity to form teratomas and differentiate into various types of cells within three germ layers). Taken together, we conclude that RE promotes the self-renewal of mGSCs and maintains the pluripotency of mGSCs, the RE serum-free and feeder-free system may be useful for the culture of pluripotent stem cell lines from adult testis tissues, which provides a new resource for tissue engineering and therapy for infertility. J. Cell. Biochem. © 2011 Wiley-Liss, Inc. PMID: 21308744 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Molecular genetics of supernumerary tooth formation. Genesis. 2011 Jan 18; Authors: Wang XP, Fan J Despite advances in the knowledge of tooth morphogenesis and differentiation, relatively little is known about the aetiology and molecular mechanisms underlying supernumerary tooth formation. A small number of supernumerary teeth may be a common developmental dental anomaly, while multiple supernumerary teeth usually have a genetic component and they are sometimes thought to represent a partial third dentition in humans. Mice, which are commonly used for studying tooth development, only exhibit one dentition, with very few mouse models exhibiting supernumerary teeth similar to those in humans. Inactivation of Apc or forced activation of Wnt/β-catenin signalling results in multiple supernumerary tooth formation in both humans and in mice, but the key genes in these pathways are not very clear. Analysis of other model systems with continuous tooth replacement or secondary tooth formation, such as fish, snake, lizard, and ferret, is providing insights into the molecular and cellular mechanisms underlying succesional tooth development, and will assist in the studies on supernumerary tooth formation in humans. This information, together with the advances in stem cell biology and tissue engineering, will pave ways for the tooth regeneration and tooth bioengineering. © 2011 Wiley-Liss, Inc. PMID: 21309064 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Micromechanical regulation in cardiac myocytes and fibroblasts: implications for tissue remodeling. Pflugers Arch. 2011 Feb 11; Authors: Curtis MW, Russell B Cells of the myocardium are at home in one of the most mechanically dynamic environments in the body. At the cellular level, pulsatile stimuli of chamber filling and emptying are experienced as cyclic strains (relative deformation) and stresses (force per unit area). The intrinsic characteristics of tension-generating myocytes and fibroblasts thus have a continuous mechanical interplay with their extrinsic surroundings. This review explores the ways that the micromechanics at the scale of single cardiac myocytes and fibroblasts have been measured, modeled, and recapitulated in vitro in the context of adaptation. Both types of cardiac cells respond to externally applied strain, and many of the intracellular mechanosensing pathways have been identified with the careful manipulation of experimental variables. In addition to strain, the extent of loading in myocytes and fibroblasts is also regulated by cues from the microenvironment such as substrate surface chemistry, stiffness, and topography. Combinations of these structural cues in three dimensions are needed to mimic the micromechanical complexity derived from the extracellular matrix of the developing, healthy, or pathophysiologic heart. An understanding of cardiac cell micromechanics can therefore inform the design and composition of tissue engineering scaffolds or stem cell niches for future applications in regenerative medicine. PMID: 21308471 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bioconjugation of hydrogels for tissue engineering. Curr Opin Biotechnol. 2011 Feb 7; Authors: Jabbari E Success of tissue engineered constructs in regenerative medicine is limited by the lack of cellmatrix interactions to guide devleopment of the seeded cells into the desired tissue. This review highlights the most exciting developments in bioconjugation of synthetic hydrogels targeted to tissue engineering. Application of conjugation techniques has resulted in the synthesis of novel biomimetic cell-responsive hydrogels to control the cascade of cell migration, adhesion, survival, differentiation, and maturation to the desired lineage concurrent with matrix remodeling. The future outlook includes developing conjugated patterned hydrogel matrices, developing novel hydrogel matrices to support self-renewal and pluripotency of embryonic and adult stem cells, and merging 3D printing with bioconjugation to fabricate hydrogels with anatomical arrangement of cells and biomolecules. PMID: 21306888 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A semi-degradable composite scaffold for articular cartilage defects. J Biomed Mater Res A. 2011 Feb 9; Authors: Scholten PM, Ng KW, Joh K, Serino LP, Warren RF, Torzilli PA, Maher SA Few options exist to replace or repair damaged articular cartilage. The optimal solution that has been suggested is a scaffold that can carry load and integrate with surrounding tissues; but such a construct has thus far been elusive. The objectives of this study were to manufacture and characterize a nondegradable hydrated scaffold. Our hypothesis was that the polymer content of the scaffold can be used to control its mechanical properties, while an internal porous network augmented with biological agents can facilitate integration with the host tissue. Using a two-step water-in-oil emulsion process a porous polyvinyl alcohol (PVA) hydrogel scaffold combined with alginate microspheres was manufactured. The scaffold had a porosity of 11-30% with pore diameters of 107-187 μm, which readily allowed for movement of cells through the scaffold. Alginate microparticles were evenly distributed through the scaffold and allowed for the slow release of biological factors. The elastic modulus (E(s) ) and Poisson's ratio (υ), Aggregate modulus (H(a) ) and dynamic modulus (E(D) ) of the scaffold were significantly affected by % PVA, as it varied from 10 to 20% wt/vol. E(s) and υ were similar to that of articular cartilage for both polymer concentrations, while H(a) and E(D) were similar to that of cartilage only at 20% PVA. The ability to control scaffold mechanical properties, while facilitating cellular migration suggest that this scaffold is a potentially viable candidate for the functional replacement of cartilage defects. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2011. PMID: 21308980 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A novel flow bioreactor for in vitro microvascularization. Tissue Eng Part C Methods. 2010 Oct;16(5):1191-200 Authors: Lee EJ, Niklason LE Although the importance of fluid flow for proper vascular development and function in vivo is well recognized, microvascular formation in response to flow has not been well evaluated in a three-dimensional (3D) environment in vitro. In this study, we developed a novel 3D in vitro perfusion system that allows direct investigation of the effects of shear stress on the development of microvasculature in vitro. This system utilizes a 3D collagen gel for suspension of vascular cells and mesenchymal stem cells, through which flow is directly perfused. We characterized the flow conditions and demonstrate the impact of flow on the development of microvasculature using a coculture of endothelial cells and mesenchymal stem cells. With the unique ability to apply bulk flow through the collagen gels, and to estimate shear stress within the constructs, this perfusion system provides a flexible platform for developing a controllable biomimetic environment that can be adapted for a variety of investigations of microvascularization. PMID: 20170423 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue engineering: Blood vessels on demand. Nature. 2011 Feb 10;470(7333):143 Authors: PMID: 21307902 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Osteoblasts on Rod Shaped Hydroxyapatite Nanoparticles incorporated PCL Film Provide an Optimal Osteogenic Niche for Stem Cell Differentiation. Tissue Eng Part A. 2011 Feb 9; Authors: Lu Z, Roohani I, Kwok PC, Zreiqat H Following the clinical insertion of a bone biomaterial, the surrounding osteoblasts would migrate and attach to the implant surface and foster a microenvironment which largely determines the differentiation fate of the co-migrated mesenchymal stem cells (MSCs). Whether the fostered microenvironment is suitable for osteogenic differentiation of MSCs is critical for the subsequent osseointegration. In this study we determined 1) how the spherical or rod shaped hydroxyapatite nanoparticles (nHA) incorporated poly( -caprolactone) (PCL) films (PCL-spherical nHA, PCL-rod nHA) interact with primary human osteoblasts (HOBs); 2) how the microenvironment rendered by their interaction affects osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ASCs). HOBs were seeded on PCL, PCL-spherical nHA and PCL-rod nHA films, respectively. When cultured alone, the HOBs on PCL-rod nHA films showed most efficient osteoblastic differentiation compared to those on PCL or PCL-spherical nHA films. When co-cultured with ASCs in an indirect co-culture system, only the HOBs on PCL-rod nHA films up-regulated the gene expression of Runx2, bone sialoprotein, and osteocalcin of ASCs. Additionally, the HOBs on PCL-rod nHA films showed significant up-regulation of BMP2 gene and protein expression and induced highest phosphorylated Smad1/5 protein level in ASCs. Treatment of the co-culture medium with BMP2 inhibitor (Noggin) largely abolished the osteogenic differentiation of the ASCs induced by the HOBs on PCL-rod nHA films. In conclusion, HOBs can not only best display their osteoblastic phenotype by culturing on PCL-rod nHA films but also render an optimal osteogenic niche for the differentiation of stem cells. PMID: 21306280 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | A key group of directors of the $3 billion California stem cell agency meets in just four business days to consider one of the more important matters facing the unique research enterprise.
The Governance Subcommittee will take up the criteria that directors would like to see in the next chair of the agency – the person who would replace Robert Klein, the longstanding (since 2003 or so) presence | | | | | | | | | | | | | | | | | | | | | | | | The California stem cell agency recently trotted out a rosy report that it commissioned about the beneficial impact of its $1.1 billion in spending so far.
CIRM's spin, however, is somewhat different than the perspective from the Pacific Research Institute.
K. Lloyd Billingsley, editorial director of the San Francisco "free market" organization, said the CIRM report is "a confession that CIRM | | | | | | | | | |  | |  | |  |
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