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Weekly Reports ㄗ105ㄘon International Trends of Cutting 每edge Life Science Development
Add Timeㄩ2013/12/16 16:31:15
1.      Overcoming hypoxia to improve tissue-engineering approaches to regenerative medicine
▽Text abstracts▼Journal of Tissue Engineering and Regenerative MedicineㄛVolume 7, Issue 7, pages 505每514, July 2013
Overcoming hypoxia to improve tissue-engineering approaches to regenerative medicine
Erik Bland1,2, Didier Dr谷au1,2,3, Karen J. L. Burg1,2,*
The current clinical successes of tissue engineering are limited primarily to low-metabolism, acellular, pre-vascularized or thin tissues. Mass transport has been identified as the primary culprit, limiting the delivery of nutrients (such as oxygen and glucose) and removal of wastes, from tissues deep within a cellular scaffold. While strategies to develop sufficient vasculature to overcome hypoxia in vitro are promising, inconsistencies between the in vitro and the in vivo environments may still negate the effectiveness of large-volume tissue-engineered scaffolds. While a common theme in tissue engineering is to maximize oxygen supply, studies suggest that moderate oxygenation of cellular scaffolds during in vitro conditioning is preferable to high oxygen levels. Aiming for moderate oxygen values to prevent hypoxia while still promoting angiogenesis may be obtained by tailoring in vitro culture conditions to the oxygen environment the scaffold will experience upon implantation. This review discusses the causes and effects of tissue-engineering hypoxia and the optimization of oxygenation for the minimization of in vivo hypoxia.
2Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients
▽Text abstracts▼British Journal of Cancer 109, 2629-2635 (12 November 2013)
Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patient
H-B Jie, N Gildener-Leapman, & J Li, et al.
Although regulatory T cells (Treg) are highly enriched in human tumours compared with peripheral blood, expression of the immune-checkpoint receptors, immunosuppressive molecules and function of Treg in these two sites remains undefined.
Tumour-infiltrating lymphocytes and peripheral blood lymphocytes were isolated from a cohort of head and neck squamous cell carcinoma (HNSCC) patients. The immunosuppressive phenotypes and function of intratumoral Treg were compared with those of peripheral blood Treg.
The frequency of immune-checkpoint receptor-positive cells was higher on intratumoral FOXP3+CD25hi Treg compared with circulating Treg (CTLA-4, P=0.002; TIM-3, P=0.002 and PD-1, P=0.002). Immunosuppressive effector molecules, LAP and ectonucleotidase CD39 were also upregulated on intratumoral FOXP3+ Treg (P=0.002 and P=0.004, respectively). CTLA-4 and CD39 were co-expressed on the majority of intratumoral FOXP3+CD4+ Treg, suggesting that these molecules have a key role in regulatory functions of these cells in situ. Notably, intratumoral Treg exhibited more potently immunosuppressive activity than circulating Treg.
These results indicate that intratumoral Treg are more immunosuppressive than circulating Treg and CTLA-4 and CD39 expressed can be potential target molecules to inhibit suppressive activities of intratumoral Treg in situ.
3.      Adipose tissue engineering using adipose-derived stem cells enclosed within an injectable carboxymethylcellulose-based hydrogel
▽Text abstracts▼Journal of Tissue Engineering and Regenerative Medicine, Volume 7, Issue 11, pages 884每892, November 2013
Adipose tissue engineering using adipose-derived stem cells enclosed within an injectable carboxymethylcellulose-based hydrogel
Yuko Ogushi, Shinji Sakai, & Koei Kawakami, et al.
In situ gelation of an aqueous solution of carboxymethylcellulose derivative bearing phenolic hydroxyl groups (CMC-Ph) that contained suspended adipose-derived stem cells (ASCs) was studied in vitro and in vivo for evaluating feasibility in adipose tissue-engineering strategies. The rat ASCs that were enclosed in the CMC-Ph gels through a horseradish peroxidase-catalysed reaction showed 92.8% viability, good proliferation and adipogenic differentiation in vitro. Ten weeks after the subcutaneous injection of ASCs-suspending CMC-Ph for in situ gelation, clearly visible new vascularized adipose tissue formed at the injection site. The number of blood vessels and the area occupied by adipose tissues were five and eight times larger, respectively, than those found in the implanted acellular gel. The adipogenesis and neovascularization were further enhanced by incorporation of fibroblast growth factor into the CMC-Ph gel containing ASCs.
4.      Noninvasive Measurement of Intestinal Inflammation After Burn Injury
▽Text abstracts▼Journal of Burn Care & Research: November/December 2013 - Volume 34 - Issue 6 - p 633-638
Noninvasive Measurement of Intestinal Inflammation After Burn Injury
Sigman, Michael MD, Conrad, Peggie; Rendon, & Juan L. et al.
Intestinal inflammation has been linked with multiorgan failure in patients with burn and other traumatic injuries. We hypothesized that markers of intestinal inflammation are detectible noninvasively. Fecal samples were collected from seven severely burned patients and 15 control patients for the measurement of inflammatory cytokines using a multiplex assay kit. In addition, fecal levels of myeloperoxidase (MPO) and elastase were measured using standard procedures. Compared with a control group, levels of inflammatory cytokines were significantly increased in the burn group. Interleukin (IL)-6 increased to a mean (㊣ SEM) of 2.16 ㊣ 0.61 to 3.81 ㊣ 0.49 pg/mg (P < .05), as did IL-8 (3.32 ㊣ 0.76 to 20.51 ㊣ 6.65 pg/mg; P < .05), IL-12 (6.23㊣0.98 to 8.11㊣0.95pg/mg; P=0.01), IL-13 (3.86 ㊣ 0.32 to 11.83 ㊣ 1.47 pg/mg; P < .05), monocyte chemoattractant protein-1 (2.78 ㊣ 2.61 to 6.5 ㊣ 3.97 pg/mg; P < .05), MPO (13.41 ㊣ 1.40 to 24.52 ㊣ 4.31 units/mg protein; P < .05), and elastase (2.46 ㊣ 0.38 to 5.08 ㊣ 0.72 pg/mL; P < .05). Our results suggest that markers of intestinal inflammation are measurable by noninvasive means and are increased after burn injury compared with controls. Of note, increased IL-8 correlated with increased MPO and elastase activity, suggesting a role for neutrophil activation in burn-mediated intestinal inflammation. Thus, these inflammatory cytokine profiles may be valuable biomarkers of intestinal inflammation after burn injury.
5.      Alimentary &green* proteins as electrospun scaffolds for skin regenerative engineering
▽Text abstracts▼Journal of Tissue Engineering and Regenerative Medicineㄛ Volume 7, Issue 12, pages 994每1008, December 2013
Alimentary &green* proteins as electrospun scaffolds for skin regenerative engineering
Leko Lin, Anat Perets, & Yah-el Har-el et al.
As a potential alternative to currently available skin substitutes and wound dressings, we explored the use of bioactive scaffolds made of plant-derived proteins. We hypothesized that &green* materials, derived from renewable and biodegradable natural sources, may confer bioactive properties to enhance wound healing and tissue regeneration. We optimized and characterized fibrous scaffolds electrospun from soy protein isolate (SPI) with addition of 0.05% poly(ethylene oxide) (PEO) dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol, and from corn zein dissolved in glacial acetic acid. Fibrous mats electrospun from either of these plant proteins remained intact without further cross-linking, possessing a skin-like pliability. Soy-derived scaffolds supported the adhesion and proliferation of cultured primary human dermal fibroblasts. Using targeted PCR arrays and qPCR validation, we found similar gene expression profiles of fibroblasts cultured for 2 and 24 h on SPI substrates and on collagen type I at both time points. On both substrates there was a pronounced time-dependent upregulation of several genes related to ECM deposition remodelling, including MMP-10, MMP-1, collagen VII, integrin-汐2 and laminin-汕3, indicating that both plant- and animal-derived materials induce similar responses from the cells after initial adhesion, degrading substrate proteins and depositing extracellular matrix in a &normal* remodelling process. These results suggest that &green* proteins, such as soy and zein, are promising as a platform for organotypic skin equivalent culture, as well as implantable scaffolds for skin regeneration. Future studies will determine specific mechanisms of their interaction with skin cells and their efficacy in wound-healing applications.

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