| 1. |
- Abdel-Khalik, Jonas, et al.
(författare)
-
Bile acid biosynthesis in Smith-Lemli-Opitz syndrome bypassing cholesterol: Potential importance of pathway intermediates.
- 2021
-
Ingår i: The Journal of steroid biochemistry and molecular biology. - : Elsevier BV. - 1879-1220 .- 0960-0760. ; 206
-
Tidskriftsartikel (refereegranskat)abstract
- Bile acids are the end products of cholesterol metabolism secreted into bile. They are essential for the absorption of lipids and lipid soluble compounds from the intestine. Here we have identified a series of unusual Δ5-unsaturated bile acids in plasma and urine of patients with Smith-Lemli-Opitz syndrome (SLOS), a defect in cholesterol biosynthesis resulting in elevated levels of 7-dehydrocholesterol (7-DHC), an immediate precursor of cholesterol. Using liquid chromatography - mass spectrometry (LC-MS) we have uncovered a pathway of bile acid biosynthesis in SLOS avoiding cholesterol starting with 7-DHC and proceeding through 7-oxo and 7β-hydroxy intermediates. This pathway also occurs to a minor extent in healthy humans, but elevated levels of pathway intermediates could be responsible for some of the features SLOS. The pathway is also active in SLOS affected pregnancies as revealed by analysis of amniotic fluid. Importantly, intermediates in the pathway, 25-hydroxy-7-oxocholesterol, (25R)26-hydroxy-7-oxocholesterol, 3β-hydroxy-7-oxocholest-5-en-(25R)26-oic acid and the analogous 7β-hydroxysterols are modulators of the activity of Smoothened (Smo), an oncoprotein that mediates Hedgehog (Hh) signalling across membranes during embryogenesis and in the regeneration of postembryonic tissue. Computational docking of the 7-oxo and 7β-hydroxy compounds to the extracellular cysteine rich domain of Smo reveals that they bind in the same groove as both 20S-hydroxycholesterol and cholesterol, known activators of the Hh pathway.
|
|
| 2. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
-
Human Embryonic Stem Cell-Derived Mesodermal Progenitors Display Substantially Increased Tissue Formation Compared to Human Mesenchymal Stem Cells Under Dynamic Culture Conditions in a Packed Bed/Column Bioreactor.
- 2013
-
Ingår i: Tissue engineering. Part A. - 1937-335X. ; 19:1-2, s. 175-87
-
Tidskriftsartikel (refereegranskat)abstract
- Bone tissue engineering represents a promising strategy to obviate bone deficiencies, allowing the ex vivo construction of bone substitutes with unprecedented potential in the clinical practice. Considering that in the human body cells are constantly stimulated by chemical and mechanical stimuli, the use of bioreactor is emerging as an essential factor for providing the proper environment for the reproducible and large-scale production of the engineered substitutes. Human mesenchymal stem cells (hMSCs) are experimentally relevant cells but, regardless the encouraging results reported after culture under dynamic conditions in bioreactors, show important limitations for tissue engineering applications, especially considering their limited proliferative potential, loss of functionality following protracted expansion, and decline in cellular fitness associated with aging. On the other hand, we previously demonstrated that human embryonic stem cell-derived mesodermal progenitors (hES-MPs) hold great potential to provide a homogenous and unlimited source of cells for bone engineering applications. Based on prior scientific evidence using different types of stem cells, in the present study we hypothesized that dynamic culture of hES-MPs in a packed bed/column bioreactor had the potential to affect proliferation, expression of genes involved in osteogenic differentiation, and matrix mineralization, therefore resulting in increased bone-like tissue formation. The reported findings suggest that hES-MPs constitute a suitable alternative cell source to hMSCs and hold great potential for the construction of bone substitutes for tissue engineering applications in clinical settings.
|
|
| 3. |
- de Peppo, Giuseppe Maria, et al.
(författare)
-
Human embryonic stem cell-derived mesodermal progenitors display substantially increased tissue formation compared to human mesenchymal stem cells under dynamic culture conditions in a packed Bed/Column bioreactor
- 2013
-
Ingår i: Tissue Engineering. Part A. - : Mary Ann Liebert Inc. - 1937-3341 .- 1937-335X. ; 19:1-2, s. 175-187
-
Tidskriftsartikel (refereegranskat)abstract
- Bone tissue engineering represents a promising strategy to obviate bone deficiencies, allowing the ex vivo construction of bone substitutes with unprecedented potential in the clinical practice. Considering that in the human body cells are constantly stimulated by chemical and mechanical stimuli, the use of bioreactor is emerging as an essential factor for providing the proper environment for the reproducible and large-scale production of the engineered substitutes. Human mesenchymal stem cells (hMSCs) are experimentally relevant cells but, regardless the encouraging results reported after culture under dynamic conditions in bioreactors, show important limitations for tissue engineering applications, especially considering their limited proliferative potential, loss of functionality following protracted expansion, and decline in cellular fitness associated with aging. On the other hand, we previously demonstrated that human embryonic stem cell-derived mesodermal progenitors (hES-MPs) hold great potential to provide a homogenous and unlimited source of cells for bone engineering applications. Based on prior scientific evidence using different types of stem cells, in the present study we hypothesized that dynamic culture of hES-MPs in a packed bed/column bioreactor had the potential to affect proliferation, expression of genes involved in osteogenic differentiation, and matrix mineralization, therefore resulting in increased bone-like tissue formation. The reported findings suggest that hES-MPs constitute a suitable alternative cell source to hMSCs and hold great potential for the construction of bone substitutes for tissue engineering applications in clinical settings.
|
|
| 4. |
- de Peppo, Giuseppe Maria, et al.
(författare)
-
Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
- 2014
-
Ingår i: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 9:1, s. 2499-2515
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role inthe osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenicdifferentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration.
|
|
| 5. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
-
Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
- 2014
-
Ingår i: International journal of nanomedicine. - : Informa UK Limited. - 1176-9114 .- 1178-2013. ; 9:1, s. 2499-2515
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role in the osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenic differentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Lindgren, Johan, et al.
(författare)
-
Interpreting melanin-based coloration through deep time : A critical Review
- 2015
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : Royal Society of London. - 0962-8452 .- 1471-2954. ; 282:1813
-
Forskningsöversikt (refereegranskat)abstract
- Colour, derived primarily from melanin and/or carotenoid pigments, is integral to many aspects of behaviour in living vertebrates, including social signalling, sexual display and crypsis. Thus, identifying biochromes in extinct animals can shed light on the acquisition and evolution of these biological traits. Both eumelanin and melanin-containing cellular organelles (melanosomes) are preserved in fossils, but recognizing traces of ancient melanin-based coloration is fraught with interpretative ambiguity, especially when observations are based on morphological evidence alone. Assigning microbodies (or, more often reported, their ‘mouldic impressions’) as melanosome traces without adequately excluding a bacterial origin is also problematic because microbes are pervasive and intimately involved in organismal degradation. Additionally, some forms synthesize melanin. In this review, we survey both vertebrate and microbial melanization, and explore the conflicts influencing assessment of microbodies preserved in association with ancient animal soft tissues.We discuss the types of data used to interpret fossil melanosomes and evaluate whether these are sufficient for definitive diagnosis. Finally, we outline an integrated morphological and geochemical approach for detecting endogenous pigment remains and associated microstructures in multimillion-year-old fossils.
|
|
| 10. |
- Magnusson, Ylva, 1967, et al.
(författare)
-
Lipid imaging of human skeletal muscle using TOF-SIMS with bismuth cluster ion as a primary ion source.
- 2008
-
Ingår i: Clinical physiology and functional imaging. - 1475-0961 .- 1475-097X. ; 28:3, s. 202-9
-
Tidskriftsartikel (refereegranskat)abstract
- Intramyocellular lipids are of importance in lipid-related diseases. The techniques in this field are limited because of a lack of adequate tools for localization of various lipids. The most usual methods for the localization of lipid distribution in the skeletal muscle are histochemistry and fluorescence probes. Different chromatography methods and mass spectrometry techniques have also been used for lipid identification. Our aim was to localize the spatial distribution of lipids in their native forms by using static time-of-flight secondary-ion mass spectrometry (TOF-SIMS). Human percutaneous skeletal muscle biopsies were obtained from the middle part of the lateral vastus muscle in the right leg of healthy adolescents with a body mass index >30. Samples were prepared by high-pressure freezing, freeze-fracturing and freeze-drying, and analysed by imaging TOF-SIMS equipped with a Bi3+ cluster ion gun. In the positive spectra, we identified phosphocholine, cholesterol, diacylglycerol, phospholipids and triacylglycerol. Phosphocholine was localized to the edge of the fibre, representing the sarcoplasma or endomysium. Weak cholesterol signals were observed in the intracellular areas. High diacylglycerol and low triacylglycerol signal intensities were seen in intracellular spaces of the transversal area of the muscle fibre. In the negative spectra, we identified fatty acids. We observed co-localization of fatty acids and diacylglycerol, which may indicate lipid-storing parts of the skeletal muscle. Thus, TOF-SIMS imaging can be used to depict the heterogeneous localization of lipids in human skeletal muscle.
|
|
