| |  | | | | | NEW EMAIL OPTION We've introduced a new mobile-friendly template that can be used on mobile devices, or used as your new default template for standard emails. See more information on our blog post. | | | | | | | | | | | | |  | |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Oxygen tension differentially regulates the functional properties of cartilaginous tissues engineered from infrapatellar fat pad derived MSCs and articular chondrocytes. Osteoarthritis Cartilage. 2010 Oct;18(10):1345-54 Authors: Buckley CT, Vinardell T, Kelly DJ For current tissue engineering or regenerative medicine strategies, chondrocyte (CC)- or mesenchymal stem cell (MSC)-seeded constructs are typically cultured in normoxic conditions (20% oxygen). However, within the knee joint capsule a lower oxygen tension exists. PMID: 20650328 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Rapid cellular turnover in adipose tissue. PLoS One. 2011;6(3):e17637 Authors: Rigamonti A, Brennand K, Lau F, Cowan CA It was recently shown that cellular turnover occurs within the human adipocyte population. Through three independent experimental approaches - dilution of an inducible histone 2B-green fluorescent protein (H2BGFP), labeling with the cell cycle marker Ki67 and incorporation of BrdU - we characterized the degree of cellular turnover in murine adipose tissue. We observed rapid turnover of the adipocyte population, finding that 4.8% of preadipocytes are replicating at any time and that between 1-5% of adipocytes are replaced each day. In light of these findings, we suggest that adipose tissue turnover represents a possible new avenue of therapeutic intervention against obesity. PMID: 21407813 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A New FACS Approach Isolates hESC Derived Endoderm Using Transcription Factors. PLoS One. 2011;6(3):e17536 Authors: Pan Y, Ouyang Z, Wong WH, Baker JC We show that high quality microarray gene expression profiles can be obtained following FACS sorting of cells using combinations of transcription factors. We use this transcription factor FACS (tfFACS) methodology to perform a genomic analysis of hESC-derived endodermal lineages marked by combinations of SOX17, GATA4, and CXCR4, and find that triple positive cells have a much stronger definitive endoderm signature than other combinations of these markers. Additionally, SOX17(+) GATA4(+) cells can be obtained at a much earlier stage of differentiation, prior to expression of CXCR4(+) cells, providing an important new tool to isolate this earlier definitive endoderm subtype. Overall, tfFACS represents an advancement in FACS technology which broadly crosses multiple disciplines, most notably in regenerative medicine to redefine cellular populations. PMID: 21408072 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Functional Identification of Cell Phenotypes Differentiating from Mice Retinal Neurospheres Using Single Cell Calcium Imaging. Cell Mol Neurobiol. 2011 Mar 17; Authors: De Melo Reis RA, Schitine CS, Kofalvi A, Grade S, Cortes L, Gardino PF, Malva JO, de Mello FG Degeneration of neural retina causes vision impairment and can lead to blindness. Neural stem and progenitor cells might be used as a tool directed to regenerative medicine of the retina. Here, we describe a novel platform for cell phenotype-specific drug discovery and screening of proneurogenic factors, able to boost differentiation of neural retinal progenitor cells. By using single cell calcium imaging (SCCI) and a rational-based stimulation protocol, a diversity of cells emerging from differentiated retinal neurosphere cultures were identified. Exposure of retinal progenitor cultures to KCl or to α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) stimulated Ca(2+) transients in microtubule-associated protein 2 (MAP-2) positive neurons. Doublecortin (DCX) and polysialated neural cell adhesion molecule (PSA-NCAM) positive neuroblasts were distinguished from differentiated neurons on the basis of their response to muscimol. Ca(2+) fluxes in glial fibrillary acidic protein (GFAP) or glutamine synthetase (GS) positive cells were induced by ATP. To validate the platform, neurospheres were treated with brain-derived neurotrophic factor (BDNF) (proneurogenic) or ciliary neurotrophic factor (CNTF) (gliogenic factor). BDNF increased the percentage of differentiated cells expressing Tuj-1 sensitive to KCl or AMPA and reduced the population of cells responding to muscimol. CNTF exposure resulted in a higher number of cells expressing GFAP responding to ATP. All together, our data may open new perspectives for cell type-specific discovery of drug targets and screening of novel proneurogenic factors to boost differentiation of neural retina cells to treat degenerative retinal diseases. PMID: 21409522 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | CCL11-CCR3 Interactions Promote Survival of Anaplastic Large Cell Lymphoma Cells via ERK1/2 Activation. Cancer Res. 2011 Mar 15;71(6):2056-65 Authors: Miyagaki T, Sugaya M, Murakami T, Asano Y, Tada Y, Kadono T, Okochi H, Tamaki K, Sato S CCR3 is a specific marker of anaplastic large cell lymphoma (ALCL) cells. ALCL cells also express CCL11, a ligand for CCR3, leading to the hypothesis that CCL11 may play an autocrine role in ALCL progression. In this study, we investigated a role of CCL11 in cell survival and growth of human Ki-JK cells, established from an ALCL patient, and murine EL-4 lymphoma cells. Both Ki-JK and EL-4 cells expressed cell surface CCR3. CCL11 increased cell survival rates of Ki-JK cells in a dose-dependent manner, whereas it promoted EL-4 cell proliferation. Furthermore, CCL11 induced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in both Ki-JK cells and EL-4 cells. Cell survival and tumor proliferation promoted by CCL11 was completely blocked by inhibition of ERK phosphorylation. CCL11 induced expression of antiapoptotic proteins, Bcl-xL and survivin, in Ki-JK cells. CCL11 also enhanced tumor growth of EL-4 and Ki-JK cells in vivo. Consistent with these results, tumor cells of cutaneous ALCL expressed CCR3 and increased levels of phosphorylated ERK1/2, Bcl-xL, and survivin in situ. Thus, our findings prompt a novel therapeutic approach to treat relapses of an aggressive form of lymphoma based on the discovery that a cell surface marker of disease functions as a critical autocrine growth receptor. Cancer Res; 71(6); 2056-65. ©2011 AACR. PMID: 21406396 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative Medicine for Skin Diseases: iPS Cells to the Rescue. J Invest Dermatol. 2011 Apr;131(4):812-4 Authors: Uitto J Induced pluripotent stem (iPS) cells reprogrammed from somatic cells have the potential to differentiate, under appropriate conditions, to any cell type. Recent studies, including two papers in this issue (Bilousova et al., 2011; Tolar et al., 2011), have demonstrated that iPS cells can differentiate into keratinocytes. Thus, iPS cells may provide a novel approach to applying regenerative medicine to cutaneous diseases such as epidermolysis bullosa. PMID: 21407233 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | The Influence of Flightless I: Regeneration versus Wound Healing. J Invest Dermatol. 2011 Apr;131(4):816-7 Authors: Morasso MI The molecular mechanisms involved in organ regeneration has biomedical implications in regenerative medicine. In this issue, Waters et al. demonstrate that levels of the established negative wound healing factor Flightless I (Flii) modulate the hair follicle's capacity to regenerate a fiber-forming bulb after amputation. Still to be investigated are the specific pathways through which Flii influences regeneration as compared with wound healing. PMID: 21407235 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Osteogenic differentiation as a result of BMP-2 plasmid DNA based gene therapy in vitro and in vivo. Eur Cell Mater. 2011;21:230-42 Authors: Wegman F, Bijenhof A, Schuijff L, Oner FC, Dhert WJ, Alblas J Bone regeneration is one of the major focus points in the field of regenerative medicine. A well-known stimulus of bone formation is bone morphogenetic protein-2 (BMP-2), which has already been extensively used in clinical applications. We investigated the possibility of achieving osteogenic differentiation both in vitro and in vivo as a result of prolonged presence of BMP-2 using plasmid DNA-based gene therapy. By delivering BMP-2 cDNA in an alginate hydrogel, a versatile formulation is developed. High transfection efficiencies of up to 95% were obtained in both human multipotent stromal cells (MSCs) and MG-63 cells using naked DNA in vitro. Over a period of 5 weeks, an increasing amount of biologically active BMP-2 was released from the cells and remained present in the gel. In vivo, transfected cells were found after both two and six weeks implantation in naked mice, even in groups without seeded cells, thus indicating in vivo transfection of endogenous cells. The protein levels were effective in inducing osteogenic differentiation in vitro, as seen by elevated alkaline phosphatase (ALP) production and in vivo, as demonstrated by the production of collagen I and osteocalcin in a mineralised alginate matrix. PMID: 21409753 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Volumetric muscle loss. J Am Acad Orthop Surg. 2011;19 Suppl 1:S35-7 Authors: Grogan BF, Hsu JR, Prevention of infection, as well as bone covering and healing, is paramount in the management of limb injury with associated muscle injury. Volumetric muscle loss (VML) is the traumatic or surgical loss of skeletal muscle with resultant functional impairment. No standardized evaluation protocol exists for the characterization and quantification of VML. Clinical photographs and video recordings, range of motion measurements, manual muscle strength testing, and isokinetic muscle function testing may prove to be useful in documenting VML. Current treatment options include functional free muscle transfer and the use of advanced bracing designs. Advances in powered bracing and regenerative medicine may one day provide additional therapeutic options. Further research on VML is warranted. PMID: 21304045 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A comparative study of 3 different cartilage repair techniques. Knee Surg Sports Traumatol Arthrosc. 2011 Mar 16; Authors: Schneider U, Schmidt-Rohlfing B, Gavenis K, Maus U, Mueller-Rath R, Andereya S PURPOSE: The value of cell-free techniques in the treatment of cartilage defects remains under debate. In this study, cartilage repair of full-thickness chondral defects in the knees of Goettinger minipigs was assessed by treatment with a cell-free collagen type-I gel or a collagen type-I gel seeded with autologous chondrocytes. As a control, abrasion arthroplasty was included. METHODS: In 18 adult Goettinger minipigs, three full-thickness chondral defects were created in one knee of the hind leg. They were either treated with a cell-free collagen gel, a collagen gel seeded with 2 × 10(5)/ml chondrocytes, or left untreated. All animals were allowed unlimited weight bearing. At 6, 12, and 52 weeks, 6 animals were sacrificed. Immediately after recovery, a non-destructive biomechanical testing was performed. The repair tissue quality was evaluated histologically, and the O'Driscoll score was calculated. RESULTS: After 6 weeks, a high number of cells migrated into the initially cell-free collagen gel. After 1 year, a hyaline-like repair tissue in both groups has been created. As assessed by O'Driscoll scoring and col-II staining, repair tissue quality of the initially cell-free gel was equal to defects treated by cell-seeded collagen gel implantation after 1 year. All untreated control defects displayed a fibrous repair tissue. The mechanical properties represented by the e-modulus were inconsistent in the course of the study. CONCLUSIONS: The implantation of a cell-free collagen type-I gel can lead to a high-quality repair tissue in the Goettinger minipig that equals a cell-based procedure after 1 year postoperatively. This study demonstrates the high chondrogenic potential of the applied collagen gel, which might help to overcome the disadvantages inherent in conventional cartilage tissue engineering methods. PMID: 21409471 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Distinct and Conserved Prominin-1/CD133-Positive Retinal Cell Populations Identified across Species. PLoS One. 2011;6(3):e17590 Authors: Jászai J, Fargeas CA, Graupner S, Tanaka EM, Brand M, Huttner WB, Corbeil D Besides being a marker of various somatic stem cells in mammals, prominin-1 (CD133) plays a role in maintaining the photoreceptor integrity since mutations in the PROM1 gene are linked with retinal degeneration. In spite of that, little information is available regarding its distribution in eyes of non-mammalian vertebrates endowed with high regenerative abilities. To address this subject, prominin-1 cognates were isolated from axolotl, zebrafish and chicken, and their retinal compartmentalization was investigated and compared to that of their mammalian orthologue. Interestingly, prominin-1 transcripts-except for the axolotl-were not strictly restricted to the outer nuclear layer (i.e., photoreceptor cells), but they also marked distinct subdivisions of the inner nuclear layer (INL). In zebrafish, where the prominin-1 gene is duplicated (i.e., prominin-1a and prominin-1b), a differential expression was noted for both paralogues within the INL being localized either to its vitreal or scleral subdivision, respectively. Interestingly, expression of prominin-1a within the former domain coincided with Pax-6-positive cells that are known to act as progenitors upon injury-induced retino-neurogenesis. A similar, but minute population of prominin-1-positive cells located at the vitreal side of the INL was also detected in developing and adult mice. In chicken, however, prominin-1-positive cells appeared to be aligned along the scleral side of the INL reminiscent of zebrafish prominin-1b. Taken together our data indicate that in addition to conserved expression of prominin-1 in photoreceptors, significant prominin-1-expressing non-photoreceptor retinal cell populations are present in the vertebrate eye that might represent potential sources of stem/progenitor cells for regenerative therapies. PMID: 21407811 [PubMed - in process] | | | | | | | | | |  | |  | |  |
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