| 1. |
- Gustafsson, Håkan, et al.
(författare)
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EPR oximetry of cetuximab-treated head-and-neck tumours in a mouse model
- 2017
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Ingår i: Cell Biochemistry and Biophysics. - : Humana Press. - 1085-9195 .- 1559-0283. ; 75:3-4, s. 299-309
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Tidskriftsartikel (refereegranskat)abstract
- Head and neck squamous cell carcinoma (HNSCC) tumours are associated with high mortality despite advances in therapy. The monoclonal antibody cetuximab (Erbitux®) has been approved for the treatment of advanced HNSCC. However, only a subset of HNSC patients receiving cetuximab actually responds to treatment, underlining the need for a means to tailor treatments of individual patients. The aim of the present study was to investigate the effect of cetuximab treatment on tumour growth, on tumour partial oxygen pressure as measured by LiPc electron paramagnetic resonance oximetry and on the expression of proteins involved in tumour growth, metabolism and hypoxia. Two HNSCC cell lines, UT-SCC-2 and UT-SCC-14, were used to generate xenografts on female BALB/c (nu/nu) nude mice. Mice with xenografts were given three injections of intraperitoneal cetuximab or phosphate-buffered saline, and the tumour volume was recorded continuously. After treatment the tumour partial oxygen pressure was measured by LiPc electron paramagnetic resonance oximetry and the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, Ki-67, MCT1, MCT4, GLUT1, CAIX and HIF-1α were investigated by immunohistochemistry. In xenografts from both cell lines (UT-SCC-2 and UT-SCC-14) cetuximab had effect on the tumour volume but the effect was more pronounced on UT-SCC-14 xenografts. A higher tumour oxygenation was measured in cetuximab-treated tumours from both cell lines compared to untreated controls. Immunocytochemical staining after cetuximab treatment shows a significantly decreased expression of EGFR, pEGFR, Ki67, CAIX and nuclear HIF-1α in UT-SCC-14 tumours compared to untreated controls. MCT1 and GLUT1 were significantly decreased in tumours from both cell lines but more pronounced in UT-SCC-14 tumours. Taken together, our results show that cetuximab treatment decreases the tumour growth and increases the tumour partial oxygen pressure of HNSCC xenografts. Furthermore we found a potential connection between the partial oxygen pressure of the tumours and the expression of proteins involved in tumour growth, metabolism and hypoxia.
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| 2. |
- Jiao, Yu, et al.
(författare)
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BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage
- 2014
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Ingår i: BioMed Research International. - : Hindawi Publishing Corporation. - 2314-6133 .- 2314-6141. ; 2014
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM). Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel), in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC) integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF) treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN).
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| 3. |
- Kaiser, Andreas, et al.
(författare)
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Brain stern slice conditioned medium contains endogenous BDNF and GDNF that affect neural crest boundary cap cells in co-culture
- 2014
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1566, s. 12-23
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Tidskriftsartikel (refereegranskat)abstract
- Conditioned medium (CM), made by collecting medium after a few days in cell culture and then re-using it to further stimulate other cells, is a known experimental concept since the 1950s. Our group has explored this technique to stimulate the performance of cells in culture in general, and to evaluate stem- and progenitor cell aptitude for auditory nerve repair enhancement in particular. As compared to other mediums, all primary endpoints in our published experimental settings have weighed in favor of conditioned culture medium, where we have shown that conditioned culture medium has a stimulatory effect on cell survival. In order to explore the reasons for this improved survival we set out to analyze the conditioned culture medium. We utilized ELISA kits to investigate whether brain stem (BS) slice CM contains any significant amounts of brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF). We further looked for a donor cell with progenitor characteristics that would be receptive to BDNF and GDNF. We chose the well-documented boundary cap (BC) progenitor cells to be tested in our in vitro co-culture setting together with cochlear nucleus (CN) of the BS. The results show that BS CM contains BDNF and GDNF and that survival of BC cells, as well as BC cell differentiation into neurons, were enhanced when BS CM were used. Altogether, we conclude that BC cells transplanted into a BDNF and GDNF rich environment could be suitable for treatment of a traumatized or degenerated auditory nerve.
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| 4. |
- Kaiser, Andreas, et al.
(författare)
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The Effects of Matrigel® on the Survival and Differentiation of a Human Neural Progenitor Dissociated Sphere Culture
- 2020
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Ingår i: Anatomical Record Part A-discoveries in Molecular Cellular and Evolutionary Biology. - : Wiley. - 1552-4884 .- 1932-8494 .- 1932-8486. ; 303:3, s. 441-450
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Tidskriftsartikel (refereegranskat)abstract
- We have previously developed an in vitro organotypic culture setting in order to investigate the performance of cellular substrates transplanted to the auditory nervous system. We have utilized this system to predict the efficacy of human neural progenitor cells (HNPCs) in transplantation to the auditory nerve to facilitate regeneration of sensory auditory nerve structures in vivo and in vitro. To optimize the growth and differentiation of HNPCs we have introduced an expansion of our in vitro system, exploring the impact of a growth factor‐altered microenvironment. Here, we seeded HNPCs as a dissociated sphere culture on a hydrogel matrix coating (Matrigel®). We evaluated the performance of HNPCs by studying their survival, differentiation, and their axon‐forming capacity. In identical culture conditions, we found that the overall survival rate of HNPCs on Matrigel coated surfaces was better than that on surfaces that were not coated with Matrigel. Furthermore, cells on Matrigel differentiated into neuronal cells to a far greater extent leading to strong synaptic marker signatures. Overall, our findings show that the present Matrigel matrix setting offers an experimental environment for the HNPCs to grow where these cells show novel and promising phenotypic characteristics suitable for further in vivo transplantation to the auditory nerve.
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| 5. |
- Kale, Ajay, et al.
(författare)
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Exogenous BDNF and Chondroitinase ABC Consisted Biomimetic Microenvironment Regulates Survival, Migration and Differentiation of Human Neural Progenitor Cells Transplanted into a Rat Auditory Nerve
- 2014
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Ingår i: Neuroscience & Medicine. - : Scientific Research Publishing. - 2158-2912 .- 2158-2947. ; 5:2, s. 86-100
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Tidskriftsartikel (refereegranskat)abstract
- Current putative regeneration oriented studies express possible role of stem cell based implantation strategy in the restoration of fundamental perception of hearing. The present work utilizes arat auditory nerve (AN) directed transplantation of human neural progenitor cells (HNPCs) as acell replacement therapy for impaired auditory function. Groups of β-bungarotoxin induced auditory function compromised female rats were used to transplant HNPCs in the nerve trunk. In thetreatment groups, brain derived neurotrophic factor (BDNF), peptide amphiphile nanofiber bioactive gel (Bgel) and Chondroitinase ABC (ChABC), a digestive enzyme that cleaves the core of chondroitin sulphate proteoglycans, were added along with HNPCs while the control groups were withPA inert gel (Igel) and devoid of ChABC. Six weeks post transplantation survival, migration, and differentiation of HNPCs were studied and compared. The groups treated with BDNF and Bgelshowed improved survival and differentiation of transplanted HNPCs while the ChABC treatedgroup showed significant migration of HNPCs along the AN and elongation of neuronal fibers alongthe nerve towards the cochlear nucleus (CN) which was characterized by immunocytochemicalmarkers for human Nuclei (HuN), human mitochondria (HuM) and neuronal β-tubulin (Tuj1).These findings show that addition of BDNF and ChABC consisted Bgel environment facilitatedHNPC survival, migration and differentiation along the transplanted rat AN towards the CN. Thistransplantation strategy provides unique experimental validation for futuristic role of cell basedbiomaterial consisted neurotrophic factor application in clinically transferable treatment of sensorineural hearing loss (SNHL) along with cochlear implants (CI).
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