| 1. |
- Junker, Johan P E, 1980-, et al.
(författare)
-
Mechanical tension stimulates the transdifferentiation of fibroblasts into myofibroblasts in human burn scars
- 2008
-
Ingår i: Burns : journal of the International Society for Burn Injuries. - : Elsevier BV. - 1879-1409. ; 34:7, s. 942-6
-
Tidskriftsartikel (refereegranskat)abstract
- Scar formation as a result of burn wounds leads to contraction of the formed granulation tissue, which causes both aesthetic and functional impairment for the patient. Currently, the main treatment methods focus on stretching to prevent tissue contraction. The myofibroblasts play a key role in the contraction of granulation tissue during scar formation, but their presence should normally decrease after wound re-epithelialization. In hypertrophic scars the myofibroblasts persist and is believed to cause further hypertrophy. Previous studies have shown that mechanical tension leads to increased myofibroblast numbers in granulation tissue. In order to evaluate the effect mechanical tension as a result of stretching has on the number of myofibroblasts in burn wound scars, an in vitro model was used. This model used human burn scar biopsies which were stretched and examined after 1 and 6 days to evaluate the effect on the number of myofibroblasts. The stretching caused an increase in the number of myofibroblasts after mechanical stimulation. This indicates that mechanical stimulation using stretching induces fibroblast to myofibroblast transdifferentiation, thus underlining the importance of further investigations of optimal methods of this regime for treating burn scars.
|
|
| 2. |
- Cieślar-Pobuda, Artur, et al.
(författare)
-
The expression pattern of PFKFB3 enzyme distinguishes between induced-pluripotent stem cells and cancer stem cells.
- 2015
-
Ingår i: Oncotarget. - Albany, NY, USA : Impact Journals LLC. - 1949-2553. ; 6:30, s. 29753--29770
-
Tidskriftsartikel (refereegranskat)abstract
- Induced pluripotent stem cells (iPS) have become crucial in medicine and biology. Several studies indicate their phenotypic similarities with cancer stem cells (CSCs) and a propensity to form tumors. Thus it is desirable to identify a trait which differentiates iPS populations and CSCs. Searching for such a feature, in this work we compare the restriction (R) point-governed regulation of cell cycle progression in different cell types (iPS, cancer, CSC and normal cells) based on the expression profile of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 (PFKFB3) and phosphofructokinase (PFK1). Our study reveals that PFKFB3 and PFK1 expression allows discrimination between iPS and CSCs. Moreover, cancer and iPS cells, when cultured under hypoxic conditions, alter their expression level of PFKFB3 and PFK1 to resemble those in CSCs. We also observed cell type-related differences in response to inhibition of PFKFB3. This possibility to distinguish CSC from iPS cells or non-stem cancer cells by PFKB3 and PFK1 expression improves the outlook for clinical application of stem cell-based therapies and for more precise detection of CSCs.
|
|
| 3. |
|
|
| 4. |
- Forsberg, Sofi, 1980-
(författare)
-
Human Epidermal Growth Factor Receptors and Biological Effects of HER-directed Molecules on Skin Epithelialization
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human skin forms a biologically active barrier and maintains vital protective functions through continuous regeneration of cells within its outermost layer, the epidermis. In healthy skin, renewal of epithelial cells is a tightly regulated process in which the epidermal growth factor receptor (EGFR or HER1) and its various ligands are involved. The biological role of other EGFR family members (HER2–4) in normal and diseased human skin has gained less interest. The purpose of this work was to investigate the expression and contribution of different HERs in cultured epidermis and psoriatic skin. Epidermal regeneration was studied by fluorescence imaging of a skin explant model exposed to anti-psoriatic drugs, HER ligands or HER-blocking molecules. EGFR, HER2 and HER3 were all markedly expressed with an in vivo-like immunostaining pattern in cultured neoepidermis, whereas only low amounts of HER4 were detected at protein and mRNA levels. Re-epithelialization was associated with receptor activation. Application of HER-selective tyrosine kinase inhibitors and monoclonal antibodies reduced the proliferative activity, receptor phosphorylation and radial outgrowth from normal skin explants. Similar anti-dynamic effects were obtained with HER kinase inhibition of neoepidermis generated from psoriatic skin. Among the HER receptors, EGFR seemed to be the dominant subtype during epithelialization in vitro although HER2 and HER3 were also involved. HER2 probably functioned as a co-receptor for the kinase-deficient HER3 in neoepidermis. In vivo, expression of HER4 mRNA was detected in normal and uninvolved psoriatic skin but was virtually absent in lesional skin, a potentially important finding for HER signalling in psoriasis. This thesis demonstrates the utility of combined dynamic and biochemical analyses of re-epithelialization and highlights the role of EGFR and other HERs for epidermal growth. It also underscores the potential of HER-directed inhibition to control hyperproliferative states of the epidermis.
|
|
| 5. |
- Fossum, M., et al.
(författare)
-
Autologous in vitro cultured urothelium in hypospadias repair{star, open}
- 2007
-
Ingår i: Journal of Pediatric Urology. - : Elsevier BV. - 1477-5131 .- 1873-4898. ; 3:1, s. 10-18
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To treat severe hypospadias with a transplant of autologous in vitro cultured urothelial cells on acellular dermis. Patients and methods: During 2000-2002 six patients aged 14-44 months with severe hypospadias were treated surgically with autologous urothelial cell transplants. All were born with scrotal or perineal hypospadias and pronounced chordee. All patients were subjected to a two-staged procedure starting with repair of the chordee. Urothelial cell harvesting via bladder lavage was performed during the first operation. The neourethra was constructed by using a transplant with cultured urothelium in an on-lay fashion. Patients have been followed 3-5.5 years. Results: All six boys are voiding through their neourethra without straining and have no residual urine after micturition. Five patients are using a standing voiding position and present bell shaped, urinary flow curves. One developed a stricture treated conservatively with persisting good effect (after more than 5 years). Two developed a fistula requiring surgical correction that was uneventful. The last patient developed an obstruction in the proximal anastomosis that was treated with an internal urethrotomy. Cosmetic appearance is good in all cases with good parental satisfaction. Urethroscopy in all patients show a wide penile neourethra. Biopsies indicate a mucosal lining consisting of urothelial cells in three cases. Conclusion: This technique is feasible for treatment of a selected group of hypospadias where pronounced chordee and shortage of preputial and penile skin complicates the creation of a neourethra. It may have other clinical implications including disorders such as bladder exstrophy and cloacal malformations, as well as mutilating traumatic injuries or cancer therapy. © 2006 Journal of Pediatric Urology Company.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Fossum, Magdalena, et al.
(författare)
-
Long-term culture of human urothelial cells : a qualitative analysis
- 2005
-
Ingår i: Cells Tissues Organs. - : S. Karger AG. - 1422-6405 .- 1422-6421. ; 181:1, s. 11-22
-
Tidskriftsartikel (refereegranskat)abstract
- Today, in vitro culturing of autologous cells is an established method in the field of tissue reconstruction. It can be applied to urothelial cells and could have many clinical implications in urological reconstructive surgery. This development calls for quality controls concerning cells used for clinical treatment when cells are autotransplanted back to the patient. We have studied cultured cells in order to detect whether genetic or morphologic changes occur. Urothelial cells isolated from bladder lavage were cultured according to different protocols based on the presence or absence of feeder cells. Genetic studies were performed by means of karyotyping with standard G-banding and interphase fluorescent in situ hybridization (FISH) analyses. The morphology of these epithelial cells was judged as well as immunostaining for epithelial cell markers. In addition, to minimize the risk of feeder cell contamination, proliferation studies were performed on cultures including feeder cells that had been pretreated with different doses of mitomycin or radiation. In initial studies, when using feeder cells in each passage according to standard protocols, urothelial cells proliferated unfavourably after the fourth passage with increasing numbers of mouse cells as well as urothelial tetraploid cells. We could also show that urothelial cells from bladder lavage need feeder cells in order to establish primary cultures. Further propagation up to 14 passages was performed without feeder cells and the urothelial cells retained normal karyotypes. We also found that mitomycin treatment had its main effect on feeder cells during the first 2 h. When feeder cells were irradiated, 20 Gy was effective and no feeder cell contamination was seen. In conclusion, we found that a high standard of quality in urothelial cell culturing can be achieved with a careful culturing technique.
|
|
| 9. |
|
|
| 10. |
- Fransson, Rebecca, et al.
(författare)
-
Exploration and pharmacokinetic profiling of phenylalanine based carbamates as novel substance p 1-7 analogues
- 2014
-
Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 5:12, s. 1272-1277
-
Tidskriftsartikel (refereegranskat)abstract
- The bioactive metabolite of Substance P, the heptapeptide SP1-7 (H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), has been shown to attenuate signs of hyperalgesia in diabetic mice, which indicate a possible use of compounds targeting the SP1-7 binding site as analgesics for neuropathic pain. Aiming at the development of drug-like SP1-7 peptidomimetics we have previously reported on the discovery of H-Phe-Phe-NH2 as a high affinity lead compound. Unfortunately, the pharmacophore of this compound was accompanied by a poor pharmacokinetic (PK) profile. Herein, further lead optimization of H-Phe-Phe-NH2 by substituting the N-terminal phenylalanine for a benzylcarbamate group giving a new type of SP1-7 analogues with good binding affinities is reported. Extensive in vitro as well as in vivo PK characterization is presented for this compound. Evaluation of different C-terminal functional groups, i.e., hydroxamic acid, acyl sulfonamide, acyl cyanamide, acyl hydrazine, and oxadiazole, suggested hydroxamic acid as a bioisosteric replacement for the original primary amide.
|
|
