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| Keeping the Cash in California: CIRM's Rules
May 11, 2010 at 8:21 PM
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| The California Stem Cell Report aims to please. In a comment on the "parochial" item, a reader who identifies himself as Arno has asked for the specific language concerning geographic funding restrictions on research supported by the $3 billion California stem cell agenda.
We have pulled some language from the "Tools and Technologies Awards II" RFA, which is the most recent on the CIRM Web | | |
| A porous 3D cell culture micro device for cell migration study.
May 11, 2010 at 6:51 AM
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| | A porous 3D cell culture micro device for cell migration study. Biomed Microdevices. 2010 May 9; Authors: Ma L, Zhou C, Lin B, Li W Cell migration under chemoattractant is an important biological step in cancer metastasis that causes the spread of malignant tumor cells. Porous polymeric materials are widely used to mimic the extracellular matrix (ECM) environment for applications such as three dimensional (3D) cell culturing and tissue engineering. In this paper we report a novel 3D cell culture device based on porous polymeric material to study cancer migration. We fabricated a porous channel on a polymeric chip using a selective ultrasonic foaming method. We demonstrate that a chemical concentration gradient could be established through the porous channel due to the slow diffusion process. We show that significant cell migration could be observed through the porous channel within 1-2 weeks of cell culturing when metastatic M4A4-GFP breast cancer cells were induced by 20% fetal bovine serum (FBS).We also developed a mathematical model to evaluate the diffusivity and concentration gradient thr! ough the fabricated porous structure. PMID: 20455081 [PubMed - as supplied by publisher] | | |
| Novel PDMS cylindrical channels that generate coaxial flow, and application to fabrication of microfibers and particles.
May 11, 2010 at 6:51 AM
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| | Novel PDMS cylindrical channels that generate coaxial flow, and application to fabrication of microfibers and particles. Lab Chip. 2010 May 7; Authors: Kang E, Shin SJ, Lee KH, Lee SH In this paper, we introduce a novel cylindrical channel that generates coaxial flow without using glass microcapillary or complicated silicon processing, and we demonstrate the fabrication of microparticles and microfibers using this channel. The simple fabrication process for cylindrical channels employs the deflection of free-standing thin PDMS membranes. Using this channel, alginate microparticles and microfibers were fabricated without clogging the downstream channel, and the dimensions of these particles and fibers could be successfully controlled by regulating the flow rate through the channels. We also developed a method to integrate the coaxial flow channel into rectangular microfluidic channel devices, which have a broad array of established applications. As proof of concept of this technology, we fabricated a microfluidic chip that incorporated 12 rectangular micromixers to generate a stepwise gradient across discrete output streams. These output streams! simultaneously fed into 5 coaxial flow channels, each of which produced a microfiber of a different chemical composition. The fibers or particles generated by the proposed method may be used in biomedical and tissue engineering, as well as in drug delivery. We expect that our method will facilitate the construction of microfluidic factories within single PDMS devices. PMID: 20454720 [PubMed - as supplied by publisher] | | |
| Dental Tissue Regeneration - A Mini-Review.
May 11, 2010 at 6:51 AM
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| | Dental Tissue Regeneration - A Mini-Review. Gerontology. 2010 May 6; Authors: Yen AH, Yelick PC Background: With today's 21st century technological advancements, it is expected that individuals will either retain their natural teeth or obtain functional tooth replacements throughout their entire life. Modern dental therapies for the replacement of missing teeth largely utilize partial or complete dentures and titanium implants capped with prosthetic crowns. Although these prostheses serve a purpose, they are not equivalent, neither in function nor aesthetics, to natural teeth. Recent progress in dental tissue engineering has lent significant credibility to the concept that biological replacement teeth therapies may soon be available to replace missing teeth. Objective: In this review, we summarize the emerging concepts of whole-tooth replacement strategies, using postnatal dental stem cells (DSCs) and dental tissue engineering approaches. Methods: We provide a thorough and extensive review of the literature. Results: Current approaches to achieve clinically ! relevant biological replacement tooth therapies rely on the cultivation of DSCs capable of relaying odontogenic induction signals, through dental epithelial-mesenchymal cell interactions. DSC expansion and differentiation can be achieved by programming progenitor stem cells to adopt dental lineages, using instructive, bioengineered scaffold materials. Periodontal ligament regeneration in particular has demonstrated significant progress recently, despite the somewhat unpredictable clinical outcomes, with regard to its capacity to augment conventional metallic dental implants and as an important component for whole-tooth tissue engineering. Following recent advances made in DSC and tissue engineering research, various research groups are in the midst of performing 'proof of principle' experiments for whole-tooth regeneration, with associated functional periodontal tissues. This mini-review focuses on recent and promising developments in the fields of pulp and periodontal tiss! ue DSCs that are of particular relevance for dental tissue and! whole-t ooth regeneration. Conclusion: Continued advances in the derivation of useable DSC populations and optimally designed scaffold materials unequivocally support the feasibility of dental tissue and whole-tooth tissue engineering. PMID: 20453484 [PubMed - as supplied by publisher] | | |
| Enzyme-triggered self-assembly of a small molecule: a supramolecular hydrogel with leaf-like structures and an ultra-low minimum gelation concentration.
May 11, 2010 at 6:51 AM
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| | Enzyme-triggered self-assembly of a small molecule: a supramolecular hydrogel with leaf-like structures and an ultra-low minimum gelation concentration. Nanotechnology. 2010 May 7;21(22):225606 Authors: Wang H, Ren C, Song Z, Wang L, Chen X, Yang Z We report on the use of a phosphatase to assist the formation of leaf-like structures and a supramolecular hydrogel with an ultra-low minimum gelation concentration. The compound can gel water at a minimum gelation concentration of 0.01 wt%, which is the lowest gelation concentration reported up to now. The images obtained by transmission electron microscopy (TEM) reveal the existence of leaf-like structures serving as the matrix of the hydrogels. The stability of the hydrogels was studied and emission spectra were used to get information about the molecular packing in the leaf-like structures. Since lowering the concentration of the gelator decreases the toxicity of the resulting hydrogels, ultra-low concentration gels have potential uses as biocompatible biomaterials for, e.g., cell cultures, tissue engineering, and drug delivery. PMID: 20453274 [PubMed - as supplied by publisher] | | |
| Influence of platelet-rich plasma on proliferation and osteogenic differentiation of skeletal muscle satellite cells: An in vitro study.
May 11, 2010 at 6:51 AM
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| | Influence of platelet-rich plasma on proliferation and osteogenic differentiation of skeletal muscle satellite cells: An in vitro study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 May 7; Authors: Huang S, Wang Z OBJECTIVES: Platelet-rich plasma (PRP) is a new application of tissue engineering and a developing area for researchers and clinicians. The aim of this study was to assess the effect of PRP on the proliferation and osteogenic differentiation of skeletal muscle satellite cell (MSC) population and the ability of PRP to induce the production of some osteogeneic-related factors in vitro. STUDY DESIGN: The PRP was obtained from Sprague-Dawley rats using 2 centrifugation techniques. Primary cultures of rat MSCs were exposed to various concentrations of PRP (0.16 x 10(8), 0.625 x 10(8), and 2.5 x 10(8) thrombocytes/carrier) on MSC proliferation using an MTT proliferation assay. Alkaline phosphatase (ALP) activity, Alizarin red S (AR) staining, calcium analyses and real-time reverse-transcription polymerase chain reaction (RT-PCR) of osteogenic-related genes were performed to study the effect of PRP on osteogenic differentiation of cultured MSCs population. RESULTS: The p! latelet concentration and growth factors (GFs) in our PRP preparations were significantly higher than in the whole blood. PRP showed a dose-dependent stimulation of cell proliferation. The maximum effect was achieved with a concentration of 0.625 x 10(8) thrombocytes/carrier. ALP activity, AR staining, and calcium analyses showed enhanced cell osteogenic differentiation in the PRP group. The real-time RT-PCR results showed that PRP up-regulated osteocalcin at day 14 and type I collagen and osteopontin at day 7 compared with the control group. CONCLUSIONS: The results of this study suggest that PRP containing osteoinductive GFs stimulates cell proliferation and osteogenic differentiation of rat-derived MSCs in vitro. PMID: 20452253 [PubMed - as supplied by publisher] | | |
| Osteogenic induction of hBMSCs by electrospun scaffolds with dexamethasone release functionality.
May 11, 2010 at 6:51 AM
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| | Osteogenic induction of hBMSCs by electrospun scaffolds with dexamethasone release functionality. Biomaterials. 2010 May 6; Authors: Martins A, Duarte AR, Faria S, Marques AP, Reis RL, Neves NM Electrospun structures were proposed as scaffolds owing to their morphological and structural similarities with the extracellular matrix found in many native tissues. These fibrous structures were also proposed as drug release systems by exploiting the direct dependence of the release rate of a drug on the surface area. An osteogenic differentiation factor, dexamethasone (DEX), was incorporated into electrospun polycaprolactone (PCL) nanofibers at different concentrations (5, 10, 15 and 20 wt.% polymer), in a single-step process. The DEX incorporated into the polymeric carrier is in amorphous state, as determined by DSC, and does not influence the typical nanofibers morphology. In vitro drug release studies demonstrated that the dexamethasone release was sustained over a period of 15 days. The bioactivity of the released dexamethasone was assessed by cultivating human bone marrow mesenchymal stem cells (hBMSCs) on 15 wt.% DEX-loaded PCL NFMs, under dexamethasone-a! bsent osteogenic differentiation medium formulation. An increased concentration of alkaline phosphatase and deposition of a mineralized matrix was observed. Phenotypic and genotypic expression of osteoblastic-specific markers corroborates the osteogenic activity of the loaded growth/differentiation factor. Overall data suggests that the electrospun biodegradable nanofibers can be used as carriers for the sustained release of growth/differentiation factors relevant for bone tissue engineering strategies. PMID: 20452016 [PubMed - as supplied by publisher] | | |
| Cartilage tissue engineering using funnel-like collagen sponges prepared with embossing ice particulate templates.
May 11, 2010 at 6:51 AM
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| | Cartilage tissue engineering using funnel-like collagen sponges prepared with embossing ice particulate templates. Biomaterials. 2010 May 6; Authors: Lu H, Ko YG, Kawazoe N, Chen G Three-dimensional porous scaffolds of collagen have been widely used for tissue engineering and regenerative medicine. In this study, we fabricated funnel-like collagen sponges with open surface pore structures by a freeze-drying method that used embossing ice particulates as a template. By controlling the size of the ice particulates and the temperature of freezing, collagen sponges with different pore structures were prepared. To investigate the effects of different pore structures on cartilage regeneration, the funnel-like collagen sponges were used to culture bovine articular chondrocytes. Scaffolds that were prepared with 400mum ice particulate templates and a freezing temperature of -3 degrees C resulted in the best cell distribution, ECM production, and chondrogenesis. Although funnel-like collagen sponges prepared with 400mum ice particulate templates and a freezing temperature of -1 degrees C and 720mum ice particulates and a freezing temperature of -3 de! grees C, showed even cell distribution, the cell seeding efficiencies and sGAG amount per cell were low. However, the scaffolds prepared with 400mum ice particulate templates and a freezing temperature of -5 degrees C or -10 degrees C showed a limited effect on the improvement of cell distribution and chondrogenesis. Control collagen sponges without ice particulates failed to support the formation of homogenous cartilage-like tissue. These results indicate that funnel-like collagen sponges were superior to control collagen sponges and that scaffolds prepared with 400mum ice particulate templates at -3 degrees C were optimal for cartilage tissue engineering. PMID: 20452015 [PubMed - as supplied by publisher] | | |
| Human bone marrow stem cell-encapsulating calcium phosphate scaffolds for bone repair.
May 11, 2010 at 6:51 AM
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| | Human bone marrow stem cell-encapsulating calcium phosphate scaffolds for bone repair. Acta Biomater. 2010 May 5; Authors: Weir MD, Xu HH Due to its injectability and excellent osteoconductivity, calcium phosphate cement (CPC) is highly promising for orthopedic applications. However, a literature search revealed no report on human bone-marrow mesenchymal stem cell (hBMSC) encapsulation in CPC for bone tissue engineering. The aim of this study was to encapsulate hBMSCs in alginate hydrogel beads and then incorporate them into CPC, CPC-chitosan, and CPC-chitosan-fiber scaffolds. Chitosan and degradable fibers was used to mechanically reinforce the scaffolds. After 21 days, the percentage of live cells and cell density of hBMSCs inside CPC-based constructs matched those in alginate without CPC, indicating that the CPC setting-reaction did not harm the hBMSCs. The alkaline phosphate activity (ALP) was increased by 8-fold at 14-day. Mineral staining, SEM and x-ray diffraction confirmed the apatitic mineral deposited by the cells. The hBMSC-synthesized mineral amount in CPC-chitosan-fiber matched that in ! CPC without chitosan and fibers. Hence, adding chitosan and fibers which reinforced the CPC, did not compromise the hBMSC osteodifferentiation and mineral synthesis. In conclusion, hBMSCs were encapsulated in CPC and CPC-chitosan-fiber scaffolds for the first time. The encapsulated cells remained viable, osteodifferentiated, and synthesized bone minerals. These self-setting, hBMSC-encapsulating CPC-based constructs may be promising for bone tissue engineering applications. PMID: 20451676 [PubMed - as supplied by publisher] | | |
| Functionalized carbon nanotubes for potential medicinal applications.
May 11, 2010 at 6:51 AM
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| | Functionalized carbon nanotubes for potential medicinal applications. Drug Discov Today. 2010 May 5; Authors: Zhang Y, Bai Y, Yan B Functionalized carbon nanotubes display unique properties that enable a variety of medicinal applications, including the diagnosis and treatment of cancer, infectious diseases and central nervous system disorders, and applications in tissue engineering. These potential applications are particularly encouraged by their ability to penetrate biological membranes and relatively low toxicity. PMID: 20451656 [PubMed - as supplied by publisher] | | |
| Implantable MEMS compressive stress sensors: Design, fabrication and calibration with application to the disc annulus.
May 11, 2010 at 6:51 AM
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| | Implantable MEMS compressive stress sensors: Design, fabrication and calibration with application to the disc annulus. J Biomech. 2010 May 5; Authors: Glos DL, Sauser FE, Papautsky I, Bylski-Austrow DI Physiological stresses are fundamental to biomechanical testing, mechanobiological analyses, implant design, and tissue engineering. The purpose of this study was to design, fabricate, and evaluate compressive stress sensors packaged for extended, in vivo implantation in the annulus of the intervertebral disc. A commercial microelectromechanical systems (MEMS) pressure sensor die was selected as the active element for a custom stress sensor. The sensor die was modified and packaged to protect the electrical system from the biochemical and biomechanical environment. Completed sensors were calibrated under hydrostatic pressure and solid contact compression. Calibrations were performed before and after 8 weeks of in vivo implantation in a porcine disc. For the two reported sensors, stress and voltage were linearly correlated over a range of 0-1.8MPa with less than 5% change in sensitivity. Sensitivity to solid contact stress was within 10% of that from hydrostatic pr! essure. In contrast to most previous studies, in which disc pressure was measured in the fluidic nucleus pulposus, these sensors may be used to measure in vivo dynamic compressive stresses in the annulus at magnitudes typical of the musculoskeletal system in a large animal over a relatively long post-operative time. PMID: 20451207 [PubMed - as supplied by publisher] | | |
| Culture and Characterization of Mesenchymal Stem Cells from Human Gingival Tissue.
May 11, 2010 at 6:51 AM
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| | Culture and Characterization of Mesenchymal Stem Cells from Human Gingival Tissue. J Periodontol. 2010 Feb 2; Authors: Mitrano TI, Grob MS, Carrión F, Nova-Lamperti E, Luz PA, Fierro FS, Quintero A, Chaparro A, Sanz A Background: Tissue engineering, using mesenchymal stem cells (MSCs), is a recent therapeutic modality that has several advantages. MSCs have high proliferation potential and may be manipulated to permit differentiation before being transplanted, suggesting they may be an ideal candidate for regenerative procedures. Precise identification of cells capable of regenerating the periodontium is valuable since no predictable regeneration procedure has yet been described. The purpose of this study was to determine the presence of MSCs in human gingival connective tissue and their morphological and funcional characteristics. Methods: Gingival connective tissue samples were obtained from five healthy students. The samples were de-epitheliized, leaving only connective tissue. The explants were minced and cultured on tissue culture dishes for 3 to 4 weeks, after which cells were characterized by flow cytometry. Differentiation into osteogenic, chondrogenic and adipogenic lin! eages was induced and evaluated by culture staining. An immunoregulation assay was also performed. Results: The results showed that gingival tissue cells fulfill the minimal criteria proposed by the International Society for Cellular Therapy to be defined as MSCs. Cell characterization was consistently positive for CD90, CD105, CD73, CD44 and CD13 markers and negative for hematopoietic markers CD34, CD38, CD45 and CD54. We observed differentiation in positive staining of adipogenic, chondrogenic and osteogenic lineages. Furthermore, gingival cells showed immunomodulative capacity. Conclusion: Gingival connective tissue could be a reservoir of MSCs that could be utilized in regenerative procedures based on tissue engineering. PMID: 20450355 [PubMed - as supplied by publisher] | | |
| Periosteum-derived cells as an alternative to bone marrow cells for bone tissue engineering around dental implants. A histomorphometric study in beagle dogs.
May 11, 2010 at 6:51 AM
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| | Periosteum-derived cells as an alternative to bone marrow cells for bone tissue engineering around dental implants. A histomorphometric study in beagle dogs. J Periodontol. 2010 Feb 2; Authors: Ribeiro FV, Suaid FF, Ruiz KG, Salmon CR, Paparotto T, Nociti FH, Sallum EA, Casati MZ Background: The aim of this study was to investigate the potential use of periosteum-derived cells (PCs) for tissue engineering in peri-implant defects. Methods: Bone marrow cells (BMCs) and periosteum-derived cells (PCs) were harvested from seven adult beagle dogs, cultured in vitro and phenotypically characterized with regard to their osteogenic properties. The animals were then subjected to teeth extraction and, three months later, two implant sites were drilled, bone dehiscences were created and dental implants were placed. Dehiscences were randomly assigned to one of the following groups: PCs: PCs+carrier and BMCs: BMCs+carrier. After 3 months, the animals were sacrificed and the implants with adjacent hard tissues were processed for undecalcified sections. Bone-to-implant contact (BIC), bone fill within the limits of implant threads (BF), and new bone area (BA) in a zone lateral to the implant were histometrically obtained. Results: In vitro, phenotypic char! acterization demonstrated that both cell populations presented osteogenic potential, as identified by the mineral nodule formation and the expression of bone markers. Histometrically, an intergroup analysis showed that both cell-treated defects had similar BF and BIC (P >0.05) and, although a trend toward a higher BA values was found for the PCs group, there was no significant difference between the experimental groups (P >0.05). Conclusion: Periosteal and bone marrow cells presented a similar potential for bone reconstruction. As such, periosteum may be considered as an alternative source of osteogenic cells in implant dentistry. PMID: 20450354 [PubMed - as supplied by publisher] | | |
| In Vitro Mineralization by Preosteoblasts in Poly(dl-lactide-co-glycolide) Inverse Opal Scaffolds Reinforced with Hydroxyapatite Nanoparticles.
May 11, 2010 at 6:51 AM
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| | In Vitro Mineralization by Preosteoblasts in Poly(dl-lactide-co-glycolide) Inverse Opal Scaffolds Reinforced with Hydroxyapatite Nanoparticles. Langmuir. 2010 May 7; Authors: Choi SW, Zhang Y, Thomopoulos S, Xia Y Inverse opal scaffolds made of poly(dl-lactide-co-glycolide) (PLGA) and hydroxyapatite (HAp) were fabricated using cubic-closed-packed (ccp) lattices of uniform gelatin microspheres as templates and evaluated for bone tissue engineering. The scaffolds exhibited a uniform pore size (213 +/- 4.4 mum), a porosity of approximately 75%, and an excellent connectivity in three dimensions. Three different formulations were examined: pure PLGA, HAp-impregnated PLGA (PLGA/HAp), and apatite (Ap)-coated PLGA/HAp. After seeding with preosteoblasts (MC3T3-E1), the samples were cultured for different periods of time and then characterized by X-ray microcomputed tomography (micro-CT) and scanning electron microscopy to evaluate osteoinductivity in terms of the amount and spatial distribution of mineral secreted from the differentiated preosteoblasts. Our results indicate that preosteoblasts cultured in the Ap-coated PLGA/HAp scaffolds secreted the largest amount of mineral, which! was also homogeneously distributed throughout the scaffolds. In contrast, the cells in the pure PLGA scaffolds secreted very little mineral, which was mainly deposited around the perimeter of the scaffolds. These results suggest that the uniform pore structure and favorable surface properties could facilitate the uniform secretion of extracellular matrix from cells throughout the scaffold. The Ap-coated PLGA/HAp scaffold with uniform pore structure could be a promising material for bone tissue engineering. PMID: 20450216 [PubMed - as supplied by publisher] | | |
| Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures.
May 11, 2010 at 6:51 AM
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| | Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3141-5 Authors: Ploss A, Khetani SR, Jones CT, Syder AJ, Trehan K, Gaysinskaya VA, Mu K, Ritola K, Rice CM, Bhatia SN Hepatitis C virus (HCV) remains a major public health problem, affecting approximately 130 million people worldwide. HCV infection can lead to cirrhosis, hepatocellular carcinoma, and end-stage liver disease, as well as extrahepatic complications such as cryoglobulinemia and lymphoma. Preventative and therapeutic options are severely limited; there is no HCV vaccine available, and nonspecific, IFN-based treatments are frequently ineffective. Development of targeted antivirals has been hampered by the lack of robust HCV cell culture systems that reliably predict human responses. Here, we show the entire HCV life cycle recapitulated in micropatterned cocultures (MPCCs) of primary human hepatocytes and supportive stroma in a multiwell format. MPCCs form polarized cell layers expressing all known HCV entry factors and sustain viral replication for several weeks. When coupled with highly sensitive fluorescence- and luminescence-based reporter systems, MPCCs have potent! ial as a high-throughput platform for simultaneous assessment of in vitro efficacy and toxicity profiles of anti-HCV therapeutics. PMID: 20133632 [PubMed - indexed for MEDLINE] | | |
| In Vitro Effects of Direct Current Electric Fields on Adipose-derived Stromal Cells.
May 11, 2010 at 6:38 AM
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| | In Vitro Effects of Direct Current Electric Fields on Adipose-derived Stromal Cells. Biochem Biophys Res Commun. 2010 May 6; Authors: Hammerick KE, Longaker MT, Prinz FB Endogenous electric fields play an important role in embryogenesis, regeneration, and wound repair and previous studies have shown that many populations of cells, leukocytes, fibroblasts, epithelial cells, and endothelial cells, exhibit directed migration in response to electric fields. As regenerative therapies continue to explore ways to control mesenchymal progenitor cells to recreate desirable tissues, it is increasingly necessary to characterize the vast nature of biological responses imposed by physical phenomena. Murine adipose-derived stromal cells (mASCs) migrated toward the cathode in direct current (DC) fields of physiologic strength and show a dose dependence of migration rate to stronger fields. Electric fields also caused mASCs to orient perpendicularly to the field vector and elicited a transient increase in cytosolic calcium. Additionally, their galvanotactic response appears to share classic chemotactic signaling pathways that are involved in the ! migration of other cell types. Galvanotaxis is one predominant result of electric fields on mASCs and it may be exploited to engineer adult stem cell concentrations and locations within implanted grafts or toward sites of wound repair. PMID: 20452327 [PubMed - as supplied by publisher] | | |
| How to track cellular aging of mesenchymal stromal cells?
May 11, 2010 at 6:17 AM
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| | How to track cellular aging of mesenchymal stromal cells? Aging (Albany NY). 2010 Apr;2(4):224-30 Authors: Wagner W, Bork S, Lepperdinger G, Joussen S, Ma N, Strunk D, Koch C Mesenchymal stromal cells (MSC) are currently tested in a large number of clinical trials and raise high hope in regenerative medicine. These cells have to be expanded in vitro before transplantation and several studies demonstrated that long-term culture evokes continuous changes in MSC: proliferation rate decays, the cell size increases, differentiation potential is affected, chromosomal instabilities may arise and molecular changes are acquired. Long-term culture of cell preparations might also have therapeutic consequences, although this has hardly been addressed in ongoing trials so far. Reliable therapeutic regimens necessitate quality control of cellular products. This research perspective summarizes available methods to track cellular aging of MSC. We have demonstrated that gene expression changes and epigenetic modifications are continuously acquired during replicative senescence. Molecular analysis of a suitable panel of genes might provide a robust tool! to assess efficiency and safety of long-term expansion. PMID: 20453259 [PubMed - in process] | | |
| Perivascular Ancestors of Adult Multipotent Stem Cells.
May 11, 2010 at 6:17 AM
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| | Perivascular Ancestors of Adult Multipotent Stem Cells. Arterioscler Thromb Vasc Biol. 2010 May 7; Authors: Corselli M, Chen CW, Crisan M, Lazzari L, Péault B Independent studies by numerous investigators have shown that it is possible to harvest multipotent progenitor cells from diverse dissociated and cultured fetal, perinatal, and principally adult developed tissues. Despite the increasingly recognized medical value of these progenitor cells, the archetype of which remains the mesenchymal stem cell, this indirect extraction method has precluded the understanding of their native identity, tissue distribution, and frequency. Consistent with other researchers, we have hypothesized that blood vessels in virtually all organs harbor ubiquitous stem cells. We have identified, marked, and sorted to homogeneity by flow cytometry endothelial and perivascular cells in a large selection of human fetal, perinatal, and adult organs. Perivascular cells, including pericytes in the smallest blood vessels and adventitial cells around larger ones, natively express mesenchymal stem cell markers and produce in culture a long-lasting prog! eny of multilineage mesodermal progenitor cells. Herein, we review results from our and other laboratories that suggest a perivascular origin for mesenchymal stem cells and other adult progenitor cells. Recent experiments illustrate the therapeutic potential of human pericytes to regenerate skeletal muscle and promote functional recovery in the diseased heart and kidney. PMID: 20453168 [PubMed - as supplied by publisher] | | |
| Genetic control of the inflammatory T-cell response in regulatory T-cell deficient scurfy mice.
May 11, 2010 at 6:17 AM
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| | Genetic control of the inflammatory T-cell response in regulatory T-cell deficient scurfy mice. Clin Immunol. 2010 May 7; Authors: Sharma R, Ju ST IPEX (Immunodysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome is a rare, recessive disorder in patients with mutations in the foxp3 gene, the normal expression of which is required for the generation of functional regulatory T-cells. Scurfy mice also bear a mutation in the foxp3, and like IPEX patients, spontaneously develop multi-organ inflammation. As reviewed herein, breeding immune response genes into Scurfy mice has provided useful insight into how the inflammatory T-cell response is regulated in the absence of regulatory T-cells and post regulatory T-cell checkpoint. Of particular interest are those that preferentially affect the inflammatory T-cell response in an "apparent" organ-specific manner, implying that specific mechanisms of control exist for individual organs during multi-organ inflammation. PMID: 20452830 [PubMed - as supplied by publisher] | | |
| Macrophages as mediators of tumor immunosurveillance.
May 11, 2010 at 6:17 AM
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| | Macrophages as mediators of tumor immunosurveillance. Trends Immunol. 2010 May 7; Authors: Jaiswal S, Chao MP, Majeti R, Weissman IL Tumor immunosurveillance is a well-established mechanism for regulation of tumor growth. In this regard, most studies have focused on the role of T- and NK-cells as the critical immune effector cells. However, macrophages play a major role in the recognition and clearance of foreign, aged, and damaged cells. Macrophage phagocytosis is negatively regulated via the receptor SIRPalpha upon binding to CD47, a ubiquitously expressed protein. We recently showed that CD47 is up-regulated in myeloid leukemia and migrating hematopoietic progenitors, and that the level of protein expression correlates with the ability to evade phagocytosis. These results implicate macrophages in the immunosurveillance of hematopoietic cells and leukemias. The ability of macrophages to phagocytose tumor cells might be exploited therapeutically by blocking the CD47-SIRPalpha interaction. PMID: 20452821 [PubMed - as supplied by publisher] | | |
| Integrin alpha 6 regulates glioblastoma stem cells.
May 11, 2010 at 6:17 AM
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| | Integrin alpha 6 regulates glioblastoma stem cells. Cell Stem Cell. 2010 May 7;6(5):421-32 Authors: Lathia JD, Gallagher J, Heddleston JM, Wang J, Eyler CE, Macswords J, Wu Q, Vasanji A, McLendon RE, Hjelmeland AB, Rich JN Cancer stem cells (CSCs) are a subpopulation of tumor cells suggested to be critical for tumor maintenance, metastasis, and therapeutic resistance. Prospective identification and targeting of CSCs are therefore priorities for the development of novel therapeutic paradigms. Although CSC enrichment has been achieved with cell surface proteins including CD133 (Prominin-1), the roles of current CSC markers in tumor maintenance remain unclear. We examined the glioblastoma stem cell (GSC) perivascular microenvironment in patient specimens to identify enrichment markers with a functional significance and identified integrin alpha6 as a candidate. Integrin alpha6 is coexpressed with conventional GSC markers and enriches for GSCs. Targeting integrin alpha6 in GSCs inhibits self-renewal, proliferation, and tumor formation capacity. Our results provide evidence that GSCs express high levels of integrin alpha6, which can serve not only as an enrichment marker but also as a pr! omising antiglioblastoma therapy. PMID: 20452317 [PubMed - in process] | | | | 
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