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  • 1.
    Omran, Ahmed
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Atanasova, Diana
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Landgren, Filip
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Magnusson, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Sclerostin: From Molecule to Clinical Biomarker2022Inngår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, nr 9, artikkel-id 4751Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Sclerostin, a glycoprotein encoded by the SOST gene, is mainly produced by mature osteocytes and is a critical regulator of bone formation through its inhibitory effect on Wnt signaling. Osteocytes are differentiated osteoblasts that form a vast and highly complex communication network and orchestrate osteogenesis in response to both mechanical and hormonal cues. The three most commonly described pathways of SOST gene regulation are mechanotransduction, Wnt/beta-catenin, and steroid signaling. Downregulation of SOST and thereby upregulation of local Wnt signaling is required for the osteogenic response to mechanical loading. This review covers recent findings concerning the identification of SOST, in vitro regulation of SOST gene expression, structural and functional properties of sclerostin, pathophysiology, biological variability, and recent assay developments for measuring circulating sclerostin. The three-dimensional structure of human sclerostin was generated with the AlphaFold Protein Structure Database applying a novel deep learning algorithm based on the amino acid sequence. The functional properties of the 3-loop conformation within the tertiary structure of sclerostin and molecular interaction with low-density lipoprotein receptor-related protein 6 (LRP6) are also reviewed. Second-generation immunoassays for intact/biointact sclerostin have recently been developed, which might overcome some of the reported methodological obstacles. Sclerostin assay standardization would be a long-term objective to overcome some of the problems with assay discrepancies. Besides the use of age- and sex-specific reference intervals for sclerostin, it is also pivotal to use assay-specific reference intervals since available immunoassays vary widely in their methodological characteristics.

    Fulltekst (pdf)
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  • 2.
    Mak, Wing Cheung
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensor- och aktuatorsystem. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Magne, B.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Cheung, Kitt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Atanasova, Diana
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. University of Montreal, Canada.
    Thermo-rheological responsive microcapsules for time-dependent controlled release of human mesenchymal stromal cells2017Inngår i: Biomaterials Science, ISSN 2047-4830, E-ISSN 2047-4849, Vol. 5, nr 11, s. 2241-2250Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human mesenchymal stromal cells (hMSCs) are adult-source cells that have been extensively evaluated for cell-based therapies. hMSCs delivered by intravascular injection have been reported to accumulate at the sites of injury to promote tissue repair and can also be employed as vectors for the delivery of therapeutic genes. However, the full potential of hMSCs remains limited as the cells are lost after injection due to anoikis and the adverse pathologic environment. Encapsulation of cells has been proposed as a means of increasing cell viability. However, controlling the release of therapeutic cells over time to target tissue still remains a challenge today. Here, we report the design and development of thermo-rheological responsive hydrogels that allow for precise, time dependent controlled-release of hMSCs. The encapsulated hMSCs retained good viability from 76% to 87% dependent upon the hydrogel compositions. We demonstrated the design of different blended hydrogel composites with modulated strength (S parameter) and looseness of hydrogel networks (N parameter) to control the release of hMSCs from thermoresponsive hydrogel capsules. We further showed the feasibility for controlled-release of encapsulated hMSCs within 3D matrix scaffolds. We reported for the first time by a systematic analysis that there is a direct correlation between the thermo-rheological properties associated with the degradation of the hydrogel composite and the cell release kinetics. This work therefore provides new insights into the further development of smart carrier systems for stem cell therapy.

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