| 1. |
- Granath, Carl, et al.
(författare)
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Characterization of Laminins in Healthy Human Aortic Valves and a Modified Decellularized Rat Scaffold
- 2020
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Ingår i: BioResearch Open Access. - : Mary Ann Liebert. - 2164-7844 .- 2164-7860. ; 9:1, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- Aortic valve stenosis is one of the most common cardiovascular diseases in western countries and can only be treated by replacement with a prosthetic valve. Tissue engineering is an emerging and promising treatment option, but in-depth knowledge about the microstructure of native heart valves is lacking, making the development of tissue-engineered heart valves challenging. Specifically, the basement membrane (BM) of heart valves remains incompletely characterized, and decellularization protocols that preserve BM components are necessary to advance the field. This study aims to characterize laminin isoforms expressed in healthy human aortic valves and establish a small animal decellularized aortic valve scaffold for future studies of the BM in tissue engineering. Laminin isoforms were assessed by immunohistochemistry with antibodies specific for individual alpha, beta, and gamma chains. The results indicated that LN-411, LN-421, LN-511, and LN-521 are expressed in human aortic valves (n = 3), forming a continuous monolayer in the endothelial BM, whereas sparsely found in the interstitium. Similar results were seen in rat aortic valves (n = 3). Retention of laminin and other BM components, concomitantly with effective removal of cells and residual DNA, was achieved through 3 h exposure to 1% sodium dodecyl sulfate and 30 min exposure to 1% Triton X-100, followed by nuclease processing in rat aortic valves (n = 3). Our results provide crucial data on the microenvironment of valvular cells relevant for research in both tissue engineering and heart valve biology. We also describe a decellularized rat aortic valve scaffold useful for mechanistic studies on the role of the BM in heart valve regeneration.
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| 2. |
- Rossi, Fiorella, et al.
(författare)
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Differences and similarities between cancer and somatic stem cells : therapeutic implications
- 2020
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Ingår i: Stem Cell Research & Therapy. - : BMC. - 1757-6512. ; 11:1
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Forskningsöversikt (refereegranskat)abstract
- Over the last decades, the cancer survival rate has increased due to personalized therapies, the discovery of targeted therapeutics and novel biological agents, and the application of palliative treatments. Despite these advances, tumor resistance to chemotherapy and radiation and rapid progression to metastatic disease are still seen in many patients. Evidence has shown that cancer stem cells (CSCs), a sub-population of cells that share many common characteristics with somatic stem cells (SSCs), contribute to this therapeutic failure. The most critical properties of CSCs are their self-renewal ability and their capacity for differentiation into heterogeneous populations of cancer cells. Although CSCs only constitute a low percentage of the total tumor mass, these cells can regrow the tumor mass on their own. Initially identified in leukemia, CSCs have subsequently been found in cancers of the breast, the colon, the pancreas, and the brain. Common genetic and phenotypic features found in both SSCs and CSCs, including upregulated signaling pathways such as Notch, Wnt, Hedgehog, and TGF-beta. These pathways play fundamental roles in the development as well as in the control of cell survival and cell fate and are relevant to therapeutic targeting of CSCs. The differences in the expression of membrane proteins and exosome-delivered microRNAs between SSCs and CSCs are also important to specifically target the stem cells of the cancer. Further research efforts should be directed toward elucidation of the fundamental differences between SSCs and CSCs to improve existing therapies and generate new clinically relevant cancer treatments.
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