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Other papers by authors:
H Aldskogius,
C Berens,
N Kanaikina,
A Liakhovitskaia,
A Medvinsky,
M Sandelin,
S Schreiner,
M Wegner,
J Hjerling-Leffler,
E N Kozlova
Department of Neuroscience, Neuroanatomy, Uppsala University Biomedical Center, Box 587, SE-751 23 Uppsala, Sweden.
Success of cell replacement therapies for neurological disorders will depend largely on the optimization of strategies to enhance viability and control the developmental fate of stem cells after transplantation. Once transplanted, ste/progenitor cells display a tendency to maintain an undifferentiated phenotype or differentiate into inappropriate cell types. Gain and loss of function experiments have revealed key transcription factors which drive differentiation of immature ste/progenitor cells towards more mature stages and eventually to full differentiation. An attractive course of action to promote survival and direct the differentiation of transplanted stem cells to a specific cell type would therefore be to force expression of regulatory differentiation molecules in already transplanted stem cells, using inducible gene- expression systems which can be controlled from the outside. Here we explore this hypothesis by employing a tetracycline gene regulating system (Tet-On) to drive the differentiation of boundary cap neural crest stem cells (bNCSCs) toward a sensory neuron fate after transplantation. We induced the expression of the key transcription factor Runx1 in Sox10-expressing bNCSCs. Forced expression of Runx1 strongly increased transplant survival in the enriched neurotrophic environment of the DRG cavity, and was sufficient to guide differentiation of bNCSCs towards a non-peptidergic nociceptive sensory neuron phenotype both in vitro and in vivo after transplantation. These findings suggest that exogenous activation of transcription factors expression after transplantation in ste/progenitor cell grafts can be a constructive approach to control their survival as well as their differentiation to the desired type of cell and that the Tet-system is a useful tool to achieve this.
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Section on Ophthalmology, The Mayo Clinic, Rochester, Minn.
Purpose: To describe the outcome of the use of fibrin adhesive (Quixil) in penetrating trabeculectomy in a rabbit model. Methods: Fibrin adhesive was used experimentally to attach the conjunctiva and the scleral flap in two groups of 17 New Zealand albino adult rabbits (34 eyes). In the first experiment (20 eyes), the fibrin adhesive was used to reattach the tissue after conjunctival peritomy and scleral flap only in 14 eyes (experiment I). In 6 eyes (controls), the conjunctiva was attached with nylon sutures. In the second experiment (14 eyes), the fibrin adhesive was used after conjunctival peritomy, scleral flap, and penetrating trabeculectomy in 8 eyes (experiment II). In a control group of 6 eyes, nylon sutures were used to attach the scleral flap and the conjunctiva after penetrating trabeculectomy. Biomicroscopy and histopathological examinations were performed on postoperative days 1, 3, 7, 14, 21, and 30. Intraocular pressure was measured before and after surgery in the second experiment. Main outcome measures are histological presence of adhesive in the tissue, degree of capillary congestion, inflammatory reaction, collagen density [scar formation] and clinical (IOP measurements before and after surgery, conjunctival chemosis, anterior chamber reaction, presence of filtering bleb and wound leakage). Results: In experiments I and II, the adhesive was well identified histologically in the tissue as an amorphic eosinophilic substance for up to day 3 and nearly disappeared by day 7. An acute inflammatory reaction was noted for up to 14 days, which converted to chronic inflammation with collagen deposits and scar formation by day 30. Similar inflammatory reaction was observed in the control group. The adhesive had no adverse effects on ocular tissue compared with sutures. One eye in experiment II demonstrated wound dehiscence. Intraocular pressure dropped from 17.35 mmHg preoperatively to 8.28 mmHg on postoperative day 1 in experiment II, and from 17.2 mmHg to 11.5 mmHg in the controls. No significant change in intraocular pressure was noted in experiment I. Conclusions: The fibrin adhesive had no adverse effects on ocular tissue compared with sutures. It might serve as an effective substitute for conjunctival and scleral wound closure in trabeculectomy surgery.
Division of Dermatology, Vanderbilt University School of Medicine, 1301 22nd Avenue South, Ste. 3900, Nashville, TN 37232, USA. Brent.Moody@Vanderbilt.edu
BACKGROUND: Cutaneous sutures should provide good wound eversion, firm closure, and cosmetically elegant results. Simple running sutures are commonly employed in cutaneous surgery but may not always be effective in achieving wound eversion. OBJECTIVE: We compared the cosmetic results of simple running nonabsorbable sutures with running horizontal mattress sutures in primary closures of facial defects. METHODS: Fifty-five patients with facial Mohs surgery defects appropriate for primary multilayer repair were randomized into one of two arms. Either the superior or the inferior half of the wound was closed with a running horizontal mattress suture. The other half of the wound was closed with a traditional simple running suture. At 1 week, 6 weeks, and 6 months, the cosmetically superior half of the wound, if any, was blindly determined by the investigators. RESULTS: The running horizontal mattress suture was significantly more cosmetically pleasing than the simple running suture. Forty-seven patients completed the study. At the 6-month follow-up, 25 patients did better with the horizontal suture and 5 did worse, and with 17 patients, there was no clinically perceptible difference. The 6-week scores predicted the outcome at 6 months, but the 1-week scores did not. CONCLUSIONS: In primary closures of the face, the running horizontal mattress suture is a cosmetically elegant alternative to a traditional running cutaneous suture. The final scar appears smoother and flatter than those produced by traditional simple running sutures.
