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Glioblastoma multiforme involves glioma stem cells (GSCs) that are resistant to various therapeutic approaches. Here, we studied the importance of paracrine signaling in the glioma microenvironment by focusing on the celecoxib-mediated role of chemokines C–C motif ligand 2 (CCL2), C-X-C ligand 10 (CXCL10), and their receptors, CCR2 and CXCR3, in GSCs and a GSC-bearing malignant glioma model. C57BL/6 mice were injected with orthotopic GSCs intracranially and divided into groups administered either 10 or 30 mg/kg celecoxib, or saline to examine the antitumor effects associated with chemokine expression. In GSCs, we analyzed cell viability and expression of chemokines and their receptors in the presence/absence of celecoxib. In the malignant glioma model, celecoxib exhibited antitumor effects in a dose dependent manner and decreased protein and mRNA levels of Ccl2 and CxcL10 and Cxcr3 but not of Ccr2. CCL2 and CXCL10 co-localized with Nestin+ stem cells, CD16+ or CD163+ macrophages and Iba-1+ microglia. In GSCs, celecoxib inhibited Ccl2 and Cxcr3 expression in a nuclear factor-kappa B-dependent manner but not Ccr2 and CxcL10. Moreover, Ccl2 silencing resulted in decreased GSC viability. These results suggest that celecoxib-mediated regulation of the CCL2/CCR2 and CXCL10/ CXCR3 axes may partially contribute to glioma-specific antitumor effects.

Aim: One of the most troublesome complications of anal preserving surgery is anal sphincter dysfunction. The aim of this study was to evaluate functional recovery after implantation of adipose-derived stem cell (ADSC) sheets, novel biotechnology, for an anal sphincter resection animal model. Methods: Eighteen female Sprague-Dawley rats underwent removal of the nearest half of the internal and external anal sphincter muscle. Nine rats received transplantation with ADSC sheets to the resected area while the remaining rats received no transplantation. The rats were evaluated for the anal function by measuring their resting pressure before surgery and on postoperative days 1, 7, 14, 28, and 56. In addition, the rats were examined for the presence of smooth muscle and also to determine its origin. Results: The improvement of the anal pressure was significantly greater in the ADSC sheet transplantation group compared with the control group. Histologically, at the vicinity of the remaining smooth muscle, reproduction of smooth muscle was detected. Using in fluorescence in situ hybridization, the cells were shown to be from the recipient. Conclusion: Regenerative therapy using ADSC sheet has the potential to recover anal sphincter dysfunction due to anorectal surgery.

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