| 1. |
- Håkansson, Joakim, 1975, et al.
(författare)
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Individualized tissue-engineered veins as vascular grafts: A proof of concept study in pig
- 2021
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Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 15:10, s. 818-830
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Tidskriftsartikel (refereegranskat)abstract
- Personalized tissue engineered vascular grafts are a promising advanced therapy medicinal product alternative to autologous or synthetic vascular grafts utilized in blood vessel bypass or replacement surgery. We hypothesized that an individualized tissue engineered vein (P-TEV) would make the body recognize the transplanted blood vessel as autologous, decrease the risk of rejection and thereby avoid lifelong treatment with immune suppressant medication as is standard with allogenic organ transplantation. To individualize blood vessels, we decellularized vena cava from six deceased donor pigs and tested them for cellular removal and histological integrity. A solution with peripheral blood from the recipient pigs was used for individualized reconditioning in a perfusion bioreactor for seven days prior to transplantation. To evaluate safety and functionality of the individualized vascular graft in vivo, we transplanted reconditioned porcine vena cava into six pigs and analyzed histology and patency of the graft at different time points, with three pigs at the final endpoint 4-5 weeks after surgery. Our results showed that the P-TEV was fully patent in all animals, did not induce any occlusion or stenosis formation and we did not find any signs of rejection. The P-TEV showed rapid recellularization in vivo with the luminal surface covered with endothelial cells. In summary, the results indicate that P-TEV is functional and have potential for use as clinical transplant grafts.
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| 2. |
- Leiva, Maria Carmen, et al.
(författare)
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Breast cancer patient-derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments
- 2021
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Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541 .- 1097-4652. ; 236:6, s. 4709-4724
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a heterogeneous disease where the tumor microenvironment, including extracellular components, plays a crucial role in tumor progression, potentially modulating treatment response. Different approaches have been used to develop three-dimensional models able to recapitulate the complexity of the extracellular matrix. Here, we use cell-free patient-derived scaffolds (PDSs) generated from breast cancer samples that were recellularized with cancer cell lines as an in vivo-like culture system for drug testing. We show that PDS cultured MCF7 cancer cells increased their resistance against the front-line chemotherapy drugs 5-fluorouracil, doxorubicin and paclitaxel in comparison to traditional two-dimensional cell cultures. The gene expression of the environmentally adapted cancer cells was modulated in different ways depending on the drug and the concentration used. High doses of doxorubicin reduced cancer stem cell features, whereas 5-fluorouracil increased stemness and decreased the proliferative phenotype. By using PDSs repopulated with other breast cancer cell lines, T-47D and MDA-MB-231, we observed both general and cell line specific drug responses. In summary, PDSs can be used to examine the extracellular matrix influence on cancer drug responses and for testing novel compounds in in vivo-like microenvironments.
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| 3. |
- Parkinson, Gabrielle T., et al.
(författare)
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Patient-derived scaffolds as a model of colorectal cancer
- 2021
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 10:3, s. 867-882
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Tidskriftsartikel (refereegranskat)abstract
- Background Colorectal cancer is the second most common cause of cancer-related death worldwide and standardized therapies often fail to treat the more aggressive and progressive types of colorectal cancer. Tumor cell heterogeneity and influence from the surrounding tumor microenvironment (TME) contribute to the complexity of the disease and large variability in clinical outcomes. Methods To model the heterogeneous nature of colorectal cancer, we used patient-derived scaffolds (PDS), which were obtained via decellularization of surgically resected tumor material, as a growth substrate for standardized cell lines. Results After confirmation of native cell absence and validation of the structural and compositional integrity of the matrix, 89 colorectal PDS were repopulated with colon cancer cell line HT29. After 3 weeks of PDS culture, HT29 cells varied their gene and protein expression profiles considerably compared to 2D-grown HT29 cells. Markers associated with proliferation were consistently decreased, while markers associated with pluripotency were increased in PDS-grown cells compared to their 2D counterparts. When comparing the PDS-induced changes in HT29 cells with clinically relevant tumor information from individual patients, we observed significant associations between stemness/pluripotency markers and tumor location, and between epithelial-to-mesenchymal transition (EMT) markers and cancer mortality. Kaplan-Meier analysis revealed that low PDS-induced EMT correlated with worse cancer-specific survival. Conclusions The colorectal PDS model can be used as a simplified personalized tool that can potentially reveal important diagnostic and pathophysiological information related to the TME.
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| 4. |
- Ujigo, Satoshi, et al.
(författare)
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Structural Analysis of Experimentally Induced Disc Herniation-Like Changes in the Rat
- 2020
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Ingår i: Spine Surgery and Related Research. - : Japanese Society for Spine Surgery and Related Research. - 2432-261X. ; 4:2, s. 117-123
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A disc herniation has traditionally been considered as disc tissue that has slipped out from an intervertebral disc. However, it was recently suggested that the disc herniation mass is a product of bioactive substances from the disc and that the disc hernia would more likely be scar tissue than herniated disc material. In this study, we aimed to analyze the structural components of experimentally induced disc herniations and compare with scar tissue and nucleus pulposus, in the rat. Methods: Twenty-eight rats had their L4-5 discs punctured. After three weeks, the nodule that had been formed over the puncture site, scar tissue from the spine musculature, and normal nucleus pulposus were harvested and processed for further analysis. Results: Proteomics analysis demonstrated that the formed nodule was more similar to scar tissue than to nucleus pulposus. Gene expression analysis showed that there was no resemblance between any tissues when looking at inflammatory genes but that, there was a clear resemblance between the nodule and scar tissue when analyzing extracellular matrix-related genes. Analysis of the GAG and polysaccharide size distribution revealed that only the nodule and scar tissue contained the shorter versions, potentially short chain hyaluronic acid that is known to induce inflammatory responses. The hematoxylin and eosin stained sections of the nodule, disc tissue, and scar tissue indicated that the morphology of the nodule and scar tissue was very similar. Conclusions: The nodule formed after experimental disc puncture, and that resembles a disc hernia, has a more structural resemblance to scar tissue than disc tissue. The nodule is, therefore, more likely to be induced by disc-derived bioactive substances than being formed by herniated disc material.
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| 5. |
- von Kieseritzky, J., et al.
(författare)
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DendroPrime as an adhesion barrier on fracture fixation plates: an experimental study in rabbits
- 2020
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Ingår i: Journal of Hand Surgery-European Volume. - : SAGE Publications. - 1753-1934 .- 2043-6289. ; 45:7, s. 742-747
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Tidskriftsartikel (refereegranskat)abstract
- We tested the anti-adhesional effect of a new thiol-ene-based coating in a rabbit model. In 12 New Zealand white rabbits, the periosteum and cortex of the proximal phalanx of the second toe of both hind paws was scratched. Stainless steel plates were fixated with screws. One plate was coated with DendroPrime and the other left bare. The non-operated second toes of both hind paws of an additional four rabbits served as controls. Seven weeks after surgery, the soft tissue adhesion to the plates was evaluated macroscopically, and joint mobility was measured biomechanically. Toe joint mobility was about 20% greater and statistically significant in specimens with coated plates compared with the bare plates. Soft tissue overgrowth and, in some cases, synovitis or adhesions between the plate and the tendon were observed on all bare plates but not on any of the coated plates. We conclude that the thiol-ene-based coating can improve joint mobility by about 20%. This material has a potential to reduce adhesion around plates in fracture surgery.
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