Wednesday, June 2, 2010

6/3 pubmed: "regenerative medici...

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Human cord blood stem cell therapy for treatment of stress urinary incontinence.
June 2, 2010 at 7:11 AM

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Human cord blood stem cell therapy for treatment of stress urinary incontinence.

J Korean Med Sci. 2010 Jun;25(6):813-6

Authors: Lee CN, Jang JB, Kim JY, Koh C, Baek JY, Lee KJ

Our objective in this study was to evaluate the safety and efficacy of transurethral cord blood stem cell injection for treatment of stress urinary incontinence in women. Between July 2005 and July 2006, 39 women underwent transurethral umbilical cord blood stem cell injection performed by one operator at a single hospital. All patients had stress urinary incontinence. The patients were evaluated 1, 3, and 12 months postoperatively. No postoperative complications were observed. 28 patients (77.8%) were more than 50% satisfied according to the Patient's Satisfaction results after 1 month, 29 patients (83%) were more than 50% satisfied according to the Patient's Satisfaction results after 3 months, and 26 (72.2%) continuously showed more than 50% improvement after 12 months. Intrinsic sphincter deficiency and mixed stress incontinency improved in the ten patients evaluated by urodynamic study. Our results suggest that transurethral umbilical cord blood stem cell inj! ection is an effective treatment for women with all types of stress urinary incontinence.

PMID: 20514298 [PubMed - in process]

 

Some hematopoietic stem cells are more equal than others.
June 2, 2010 at 7:11 AM

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Some hematopoietic stem cells are more equal than others.

J Exp Med. 2010 May 31;

Authors: Hock H

Hematopoietic stem cells (HSCs) save lives in routine clinical practice every day, as they are the key element in transplantation-based therapies for hematologic malignancies. The success of clinical stem cell transplantation critically relies on the ability of stem cells to reconstitute the hematopoietic system for many decades after the administration of the powerful chemotherapy and/or irradiation that is required to eradicate malignant cells, but also irreversibly ablates patients' own blood forming capacity. Surprisingly, despite enormous efforts and continuous progress in the field, our understanding of the basic biology of HSCs is still rather incomplete. Several recent studies substantially refine our understanding of the cells at the very top of the hematopoietic hierarchy, and suggest that we may need to revise the criteria we typically use to identify and define HSCs.

PMID: 20513745 [PubMed - as supplied by publisher]

 

Insulin-like growth factor binding protein-3 promotes transforming growth factor-{beta}1-mediated epithelial-to-mesenchymal transition and motility in transformed human esophageal cells.
June 2, 2010 at 7:11 AM

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Insulin-like growth factor binding protein-3 promotes transforming growth factor-{beta}1-mediated epithelial-to-mesenchymal transition and motility in transformed human esophageal cells.

Carcinogenesis. 2010 May 31;

Authors: Natsuizaka M, Ohashi S, Wong GS, Ahmadi A, Kalman RA, Budo D, Klein-Szanto AJ, Herlyn M, Diehl JA, Nakagawa H

Insulin-like growth factor binding protein (IGFBP)-3 is overexpressed frequently in esophageal squamous cell carcinoma (ESCC). Yet, the role of IGFBP3 in esophageal tumor biology remains to be elucidated. We find that IGFBP3 facilitates TGF-beta1-mediated epithelial to mesenchymal transition (EMT) in transformed human esophageal epithelial cells, EPC2-hTERT-EGFR-p53(R175H). In organotypic 3D culture, a form of human tissue engineering, laser-capture microdissection revealed concurrent upregulation of transforming growth factor (TGF)-beta target genes, IGFBP3 and EMT related genes in the cells invading into the stromal compartment. IGFBP3 enhanced TGF-beta1-mediated EMT as well as transcription factors essential in EMT by allowing persistent SMAD2 and SMAD3 phosphorylation. TGF-beta1-mediated EMT and cell invasion were enhanced by ectopically expressed IGFBP3 and suppressed by RNA interference directed against IGFBP3. The IGFBP3 knockdown effect was rescued by IGFB! P3(I56G/L80G/L81G), a mutant IGFBP3 lacking an IGF binding capacity. Thus, IGFBP3 can regulate TGF-beta1-mediated EMT and cell invasion in an IGF (or IGF-1R)-independent manner. IGFBP3(I56G/L80G/L81G) also promoted EMT in vivo in a Ras-transformed human esophageal cell line T-Te-Ras upon xenograft transplantation in nude mice. In aggregate, IGFBP3 may have a novel IGF-binding independent biological function in regulation of TGF-beta1-mediated EMT and cell invasion.

PMID: 20513670 [PubMed - as supplied by publisher]

 

Flexor Tendon Reconstruction.
June 2, 2010 at 7:11 AM

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Flexor Tendon Reconstruction.

J Hand Surg Am. 2010 Jun;35(6):1025-1030

Authors: Moore T, Anderson B, Seiler JG

Successful flexor tendon repair has narrowed the indications for flexor tendon grafting. Flexor tendon grafting is the preferred method of treatment for patients with neglected digital flexor tendon lacerations and after the failure of flexor tendon repair. Improvements in tendon repair methods and in aftercare methods have improved the outcomes after flexor tendon grafting. Future improvements in tissue engineering may also improve the results of flexor tendon repair.

PMID: 20513583 [PubMed - as supplied by publisher]

 

Attenuation of the transforming growth factor beta-signaling pathway in chronic venous ulcers.
June 2, 2010 at 7:11 AM

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Attenuation of the transforming growth factor beta-signaling pathway in chronic venous ulcers.

Mol Med. 2010 Mar;16(3-4):92-101

Authors: Pastar I, Stojadinovic O, Krzyzanowska A, Barrientos S, Stuelten C, Zimmerman K, Blumenberg M, Brem H, Tomic-Canic M

Transforming growth factor beta (TGFbeta) is important in inflammation, angiogenesis, reepithelialization and connective tissue regeneration during wound healing. We analyzed components of TGFbeta signaling pathway in biopsies from 10 patients with nonhealing venous ulcers (VUs). Using comparative genomics of transcriptional profiles of VUs and TGFbeta-treated keratinocytes, we found deregulation of TGFbeta target genes in VUs. Using quantitative polymerase chain reaction (qPCR) and immunohistochemical analysis, we found suppression of TGFbeta RI, TGFbeta RII and TGFbeta RIII, and complete absence of phosphorylated Smad2 (pSmad2) in VU epidermis. In contrast, pSmad2 was induced in the cells of the migrating epithelial tongue of acute wounds. TGFbeta-inducible transcription factors (GADD45beta , ATF3 and ZFP36L1) were suppressed in VUs. Likewise, genes suppressed by TGFbeta (FABP5, CSTA and S100A8) were induced in nonhealing VUs. An inhibitor of Smad signaling, Sma! d7 was also downregulated in VUs. We conclude that TGFbeta signaling is functionally blocked in VUs by downregulation of TGFbeta receptors and attenuation of Smad signaling resulting in deregulation of TGFbeta target genes and consequent hyperproliferation. These data suggest that application of exogenous TGFbeta may not be a beneficial treatment for VUs.

PMID: 20069132 [PubMed - indexed for MEDLINE]

 

Effect of decorin and dermatan sulfate on the mechanical properties of a neocartilage.
June 2, 2010 at 7:11 AM

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Effect of decorin and dermatan sulfate on the mechanical properties of a neocartilage.

Connect Tissue Res. 2010 Apr;51(2):159-70

Authors: Lewis JL, Krawczak DA, Oegema TR, Westendorf JJ

Decorin is known to influence the size of collagen fibrils in ligaments and tendons and it has been hypothesized to provide a structural link between collagen fibrils in connective tissues, including cartilage. Coincidently, mechanical properties of skin, ligament, and tendons are altered in decorin knockout mice, suggesting it may influence the structural properties of tissue or tissue matrix organization. To further examine the role of decorin in the extracellular matrix development and subsequent material properties of cartilage, tissue (neocartilage) was grown in a 3D culture model using a pure population of genetically modified chondrocytes stably overexpressing decorin (DCN) or decorin lacking dermatan sulfate (MDCN). An empty vector (CON) served as a virus control. Following generation of the cartilage-like tissues, mechanical properties in tension and compression, collagen fibril diameter, matrix organization, and biochemistry of the tissue were determined! . There were no differences between CON and DCN tissues in any parameter measured. In contrast, tissue generated in MDCN cultures was thinner, had higher collagen density, and higher elastic moduli as compared to both CON and DCN tissues. Considering there was no difference in stiffness between CON and DCN tissues, the notion that decorin contributes to the mechanical properties via load transfer was refuted in this model. However, contrasts in the mechanical properties of the MDCN tissue suggest that the dermatan sulfate chains on decorin influences the organization/maturation and resultant mechanical properties of the matrix by as an yet-unidentified regulatory mechanism.

PMID: 20001848 [PubMed - indexed for MEDLINE]

 

Chemokine profile of human serum from whole blood: migratory effects of CXCL-10 and CXCL-11 on human mesenchymal stem cells.
June 2, 2010 at 7:11 AM

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Chemokine profile of human serum from whole blood: migratory effects of CXCL-10 and CXCL-11 on human mesenchymal stem cells.

Connect Tissue Res. 2010 Apr;51(2):113-22

Authors: Kalwitz G, Andreas K, Endres M, Neumann K, Notter M, Ringe J, Sittinger M, Kaps C

Autologous human serum is used in cartilage repair and may exert its effect by the recruitment of mesenchymal stem and progenitor cells (MSC). Aim of our study was to analyze the chemokine profile of human serum and to verify chemotactic activity of selected chemokines on MSC. Human MSC were isolated from iliac crest bone marrow aspirates. Chemotactic activity of human serum made from whole blood and pharma grade serum was tested in 96-well chemotaxis assays and chemokine levels were analyzed using human chemokine antibody membrane arrays. The chemotactic potential of selected chemokines on MSC was tested dose dependently using chemotaxis assays. Human serum derived from whole blood significantly attracted human MSC, while pharma grade serum did not recruit MSC. Human chemokine antibody array analysis showed that the level of chemokines CXCL-3, 5, 7-8, 10-12, 16; CCL- 2, 5, 11, 13, 16-20, 24-25, 27; as well as XCL-1 was elevated (fold change >1.5) in serum deri! ved from whole blood compared to nonrecruiting pharma grade serum. Chemotaxis assays showed that the chemokines IP-10/CXCL-10 and I-TAC/CXCL-11 significantly recruit human MSC. PARC/CCL-18, HCC-4/CCL-16, CTACK/CCL-27, and Lymphotactin/XCL-1 showed no chemotactic effect on MSC. Therefore, human serum derived from whole blood contains chemokines that may contribute to serum-mediated recruitment of human mesenchymal progenitors from bone marrow.

PMID: 20001843 [PubMed - indexed for MEDLINE]

 

[Biological dressing with human hair keratin-collagen sponge-poly 2-hydroxyethyl methacrylate composite promotes burn wound healing in SD rats]
June 2, 2010 at 7:11 AM

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[Biological dressing with human hair keratin-collagen sponge-poly 2-hydroxyethyl methacrylate composite promotes burn wound healing in SD rats]

Nan Fang Yi Ke Da Xue Xue Bao. 2007 Nov;27(11):1621-6

Authors: Chen YH, Dong WR, Chen QY, Zhao BL, Zou ZZ, Xiao YQ, Hu GD, Qiu XX

OBJECTIVE: To develop a composite material containing human hair keratin (HHK), collagen sponge (inner layer) and poly 2-hydroxyethyl methacrylate (PHEMA) film that allows sustained release of polydatin and test its effect as a biological dressing in promoting burn wound healing in SD rats. METHODS: Three HHK materials with fast, moderate, and low degradation rates were mixed at the ratio of 4:3:3 to prepare a reticular structure, which was processed into a composite material with bovine tendon-derived collagen sponge, and further complexed with HEMA film containing PD prepared by polymerization. Degree II burn wound was induced in SD rats by scalding and within postburn day 2-5, the wounds were cleansed and covered with the composite material or with glutaraldehyde-treated porcine skin (positive control). At week 1, 2, 4, 6 and 8 following wound dressing, 6 full-thickness skin samples were harvested from the wounds for histological observation and immunohistochem! ical detection of collagen and elastic fibers, and the wound healing time and healing rate were recorded. RESULTS: The prepared collagen sponge film was transparent and porous (50-300 microm in diameter) and allowed sustained PD release into normal saline within 48 h. Compared with the porcine skin, the composite material reduced exudation and maintained ideal moisture of the wound, and significantly shortened the wound healing time (P=0.000). On day 7, 14, and 21 following dressing, the composite material and porcine skin significantly increased the wound healing rate as compared with the negative control group (P=0.000), and on day 14, the composite achieved significantly greater healing rate than the porcine skin (P<0.05). CONCLUSION: HHK-collagen sponge-PHEMA/PD composite as a dressing material promotes burn wound healing in rats by allowing in vivo construction of tissue engineered epidermis. PHEMA is feasible for sustained drug delivery in this composite.

PMID: 18024274 [PubMed - indexed for MEDLINE]

 

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