uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Stenfelt, Sonya
Alternative names
Publications (9 of 9) Show all publications
Stenfelt, S., Blixt, M. K. E., All-Ericsson, C., Hallböök, F. & Boije, H. (2017). Heterogeneity in retinoblastoma: a tale of molecules and models. CLINICAL AND TRANSLATIONAL MEDICINE, 6, Article ID 42.
Open this publication in new window or tab >>Heterogeneity in retinoblastoma: a tale of molecules and models
Show others...
2017 (English)In: CLINICAL AND TRANSLATIONAL MEDICINE, ISSN 2001-1326, Vol. 6, article id 42Article, review/survey (Refereed) Published
Abstract [en]

Retinoblastoma, an intraocular pediatric cancer, develops in the embryonic retina following biallelic loss of RB1. However, there is a wide range of genetic and epigenetic changes that can affect RB1 resulting in different clinical outcomes. In addition, other transformations, such as MYCN amplification, generate particularly aggressive tumors, which may or may not be RB1 independent. Recognizing the cellular characteristics required for tumor development, by identifying the elusive cell-of-origin for retinoblastoma, would help us understand the development of these tumors. In this review we summarize the heterogeneity reported in retinoblastoma on a molecular, cellular and tissue level. We also discuss the challenging heterogeneity in current retinoblastoma models and suggest future platforms that could contribute to improved understanding of tumor initiation, progression and metastasis in retinoblastoma, which may ultimately lead to more patient-specific treatments.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2017
Keywords
Cancer, Cell-of-origin, Genetics, Horizontal cells, MYCN, Photoreceptors, OTX2, RB1
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-346610 (URN)10.1186/s40169-017-0173-2 (DOI)000414747600001 ()
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2019-01-22Bibliographically approved
Piskounova, S., Gedda, L., Hulsart-Billström, G., Hilborn, J. & Bowden, T. (2014). Characterization of recombinant human bone morphogenetic protein-2 delivery from injectable hyaluronan-based hydrogels by means of I-125-radiolabelling. Journal of Tissue Engineering and Regenerative Medicine, 8(10), 821-830
Open this publication in new window or tab >>Characterization of recombinant human bone morphogenetic protein-2 delivery from injectable hyaluronan-based hydrogels by means of I-125-radiolabelling
Show others...
2014 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, no 10, p. 821-830Article in journal (Refereed) Published
Abstract [en]

This study presents a thorough in vitro and in vivo characterization of the delivery of bone morphogenetic protein 2 (BMP-2) from a hyaluronan-based hydrogel system. The in vitro release of BMP-2 from similar hydrogels has previously been studied by enzyme-linked immunosorbent assay (ELISA), by which only a fraction of the loaded protein is detected. In the current study, I-125 radiolabelling was used instead to monitor BMP-2 in vitro and in vivo. To minimize protein loss during handling, I-125-BMP-2 adsorption to different tubes was studied at different times and temperatures. The data showed that Protein LoBind tubes exhibited the lowest protein affinity. Furthermore, a biphasic release profile of biologically active BMP-2 was observed both in vitro and in vivo, with the initial fast phase during the first week, followed by a slower release during the remaining 3 weeks. The initial fast-release phase corresponded to the early bone formation observed after 8 days in an ectopic model in rats. Bone volume and mineral content increased until day 14, after which a decrease in bone volume was observed, possibly due to resorption in response to decreased amounts of released BMP-2. Overall, the results suggested that cautious protein handling and a reliable quantification technique are essential factors for successful design of a BMP-2 delivery system.

Keywords
BMP-2 delivery, radioactive labeling, hyaluronan hydrogels, reproducibility, ectopic bone formation, protein adsorption
National Category
Biomaterials Science
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-158961 (URN)10.1002/term.1584 (DOI)000343059700009 ()22927307 (PubMedID)
Available from: 2011-09-19 Created: 2011-09-19 Last updated: 2018-12-04
Hulsart-Billström, G., Piskounova, S., Gedda, L., Andersson, B.-M., Bergman, K., Hilborn, J., . . . Bowden, T. (2013). Morphological differences in BMP-2-induced ectopic bone between solid and crushed hyaluronan hydrogel templates. Journal of materials science. Materials in medicine, 24(5), 1201-1209
Open this publication in new window or tab >>Morphological differences in BMP-2-induced ectopic bone between solid and crushed hyaluronan hydrogel templates
Show others...
2013 (English)In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 24, no 5, p. 1201-1209Article in journal (Refereed) Published
Abstract [en]

The possibility to affect bone formation by using crushed versus solid hydrogels as carriers for bone morphogenetic protein 2 (BMP-2) was studied. Hydrogels, based on chemical crosslinking between hyaluronic acid and poly(vinyl alcohol) derivatives, were loaded with BMP-2 and hydroxyapatite. Crushed and solid forms of the gels were analyzed both in vitro via a release study using I-125 radioactive labeling of BMP-2, and in vivo in a subcutaneous ectopic bone model in rats. Dramatically different morphologies were observed for the ectopic bone formed in vivo in the two types of gels, even though virtually identical release profiles were observed in vitro. Solid hydrogels induced formation of a dense bone shell around non-degraded hydrogel, while crushed hydrogels demonstrated a uniform bone formation throughout the entire sample. These results suggest that by crushing the hydrogel, the construct's three-dimensional network becomes disrupted. This could expose unreacted functional groups, making the fragment's surfaces reactive and enable limited chemical fusion between the crushed hydrogel fragments, leading to similar in vitro release profiles. However, in vivo these interactions could be broken by enzymatic activity, creating a macroporous structure that allows easier cell infiltration, thus, facilitating bone formation.

National Category
Engineering and Technology Natural Sciences Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-201244 (URN)10.1007/s10856-013-4877-6 (DOI)000318510200008 ()
Available from: 2013-06-10 Created: 2013-06-10 Last updated: 2018-12-04
Billström, G. H., Piskounova, S., Gedda, L., Hilborn, J., Bowden, T. & Larsson, S. (2012). Improved bone formation by altering surface area of hyaluronan-based hydrogel carrier for bone morphogenetic protein-2. Paper presented at 39th Annual Congress of the European-Calcified-Tissue-Society (ECTS), MAY 19-23, 2012, Stockholm, SWEDEN. Bone, 50, S114-S114
Open this publication in new window or tab >>Improved bone formation by altering surface area of hyaluronan-based hydrogel carrier for bone morphogenetic protein-2
Show others...
2012 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, p. S114-S114Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences Polymer Chemistry
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-177449 (URN)10.1016/j.bone.2012.02.351 (DOI)000304503500324 ()
Conference
39th Annual Congress of the European-Calcified-Tissue-Society (ECTS), MAY 19-23, 2012, Stockholm, SWEDEN
Available from: 2012-12-13 Created: 2012-07-13 Last updated: 2018-12-04
Piskounova, S., Gedda, L., Hulsart Billström, G., Hilborn, J. & Bowden, T. (2012). The importance of proper protein handling and detection for the design of a BMP-2 release system. Journal of Tissue Engineering and Regenerative Medicine, 6(s1), 322-322
Open this publication in new window or tab >>The importance of proper protein handling and detection for the design of a BMP-2 release system
Show others...
2012 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, Vol. 6, no s1, p. 322-322Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Although various promising strategies have been proposed for the delivery of BMP-2 for bone regeneration, there is currently no ideal system out on the market. Proper handling and detection of BMP-2 are two factors that are commonly overlooked, resulting in inaccurate characterization of BMP-2 delivery systems. In this work we employed radiolabeling with 125I in an attempt study the growth factor release from a hydrogel system both in vitro and in vivo. BMP-2 (InductOs, Pfizer) was radiolabeled using a modified chloramine-T method and adsorption to sample tubes was studied at different times and temperatures. In vitro release of BMP-2 was compared to the ALP expression. In vivo release was correlated to bone formation in an intramuscular ectopic model in male Sprague–Dawley rats. The results showed that Protein LoBind tubes exhibited the lowest BMP-2 adsorption. Both release studies resulted in a biphasic profile of biologically active BMP-2. Mineralization was observed in vivo after 8 days, with increasing mineral volume and mineral content until day 14. The study confirmed the superiority of radiolabeling over conventional methods such as ELISA, as well as the importance of cautions handling and reliable quantification techniques for successful design of BMP-2 delivery systems

National Category
Medical and Health Sciences Polymer Chemistry
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-182413 (URN)10.1002/term.1586 (DOI)000308313002386 ()
Available from: 2012-10-11 Created: 2012-10-10 Last updated: 2018-12-04
Piskounova, S. (2011). Biomaterials for Promoting Self-Healing of Bone Tissue. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Biomaterials for Promoting Self-Healing of Bone Tissue
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The present work addresses poor bone/implant integration and severe bone defects. In both conditions external stimuli is required for new bone to form. A multilayered functional implant coating, comprised of an inner layer of crystalline titanium dioxide (TiO2) and an outer layer of hydroxyapatite (HAP), loaded with bone morphogenetic protein-2 (BMP-2), was proposed as a tool for providing both improved initial bone formation and long-term osseointegration. The in vitro characterization of the implant coatings showed that TiO2 and HAP were more favorable for cell viability, cell morphology and initial cell differentiation, compared to native titanium oxide. Furthermore, significantly higher cell differentiation was observed on surfaces with BMP-2, indicating that a simple soaking process can be used for incorporating bioactive molecules. Moreover, the results suggest that there could be a direct interaction between BMP-2 and HAP, which prolongs the retention of the growth factor, improving its therapeutic effect.

For treating severe bone defects a strategy involving BMP-2 delivery from hyaluronan hydrogels was explored. The hydrogels were prepared from two reactive polymers – an aldehyde-modified hyaluronan and a hydrazide-modified poly(vinyl alcohol). Upon mixing, the two components formed a chemically crosslinked hydrogel. In this work the mixing of the hydrogel components was optimized by rheological measurements. Furthermore, an appropriate buffer was selected for in vitro experiments by studying the swelling of hydrogels in PBS and in cell culture medium. A detection method, based on radioactive labeling of BMP-2 with 125I was used to monitor growth factor release both in vitro and in vivo. The results showed a biphasic release profile of BMP-2, where approximately 16 %  and 3 % of the growth factor remained inside the hydrogel after 4 weeks in vitro and in vivo, respectively. The initial fast release phase corresponded to the early ectopic bone formation observed 8 d after injection of the hydrogel formulation in the thigh muscle of rats. The hydrogel formulation could be improved by incorporation of HAP powder into the hydrogel formulation. Furthermore, bone formation could be increased by pre-incubation of the premixed hydrogel components inside the syringe prior to injection. Crushed hydrogels were also observed to induce more bone formation compared to solid hydrogels, when implanted subcutaneously in rats. This was thought to be due to increased surface area of the hydrogel, which allowed for improved cell infiltration.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. p. 70
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 857
Keywords
Osseointegration, implant coating, hyaluronan hydrogel, bone morphogenetic protein-2, hydroxyapatite, bone, delivery system, injectable, mixing, radioactive labeling
National Category
Biomaterials Science Polymer Chemistry
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-158939 (URN)978-91-554-8168-1 (ISBN)
Public defence
2011-11-11, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2011-10-21 Created: 2011-09-19 Last updated: 2011-11-04Bibliographically approved
Forsgren, J., Brohede, U., Piskounova, S., Mihranyan, A., Larsson, S., Maria, S. & Engqvist, H. (2011). In Vivo Evaluation of Functionalized Biomimetic Hydroxyapatite for Local Delivery of Active Agents. Journal of Biomaterials and Nanobiotechnology, 2(2), 149-154
Open this publication in new window or tab >>In Vivo Evaluation of Functionalized Biomimetic Hydroxyapatite for Local Delivery of Active Agents
Show others...
2011 (English)In: Journal of Biomaterials and Nanobiotechnology, ISSN 2158-7027, 2158-7043, Vol. 2, no 2, p. 149-154Article in journal (Refereed) Published
Abstract [en]

This study was carried out to investigate the biological response in vivo to biomimetic hydroxyapatite implant coatings functionalized with bisphosphonates and bone morphogenetic proteins. The functionalization was carried out by a simple soaking procedure in the operating room immediately prior to surgery. Cylindrical titanium samples with and without coatings were implanted in the distal femoral epiphysis of sheep and retrieved after 6 weeks. The histological analysis proved that all samples were integrated well in the tissue with no signs of intolerance. Fewer osteoclasts were observed in the vicinity of bisphosphonate-functionalized samples and the bone was denser around these samples compared to the other samples. Samples functionalized with bone morphogenetic protein induced more bone/implant contact but showed a more inconsistent outcome with reduced bone density around the samples. This study demonstrates a simple method to functionalize implant coatings, which provides surgeons with an option of patient-specific functionalization of implants. The observed biological impact due to the delivery of active molecules from the coatings suggests that this strategy may also be employed to deliver antibiotics from similar coatings.

National Category
Engineering and Technology Polymer Chemistry
Research subject
Engineering Science with specialization in Materials Science; Engineering Science with specialization in Nanotechnology and Functional Materials; Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-156129 (URN)10.4236/jbnb.2011.22019 (DOI)
Funder
Swedish Research Council
Available from: 2011-07-11 Created: 2011-07-11 Last updated: 2018-02-08Bibliographically approved
Piskounova, S., Rojas, R., Bergman, K. & Hilborn, J. (2011). The Effect of Mixing on the Mechanical Properties of Hyaluronan-Based Injectable Hydrogels. Macromolecular materials and engineering (Print), 296(10), 944-951
Open this publication in new window or tab >>The Effect of Mixing on the Mechanical Properties of Hyaluronan-Based Injectable Hydrogels
2011 (English)In: Macromolecular materials and engineering (Print), ISSN 1438-7492, E-ISSN 1439-2054, Vol. 296, no 10, p. 944-951Article in journal (Refereed) Published
Abstract [en]

A method for determining the correlation between the mixing of two reactive polymers and the structural and mechanical properties of the formed hydrogels is presented. Rheological measurements show that insufficient mixing gives rise to soft and not fully crosslinked hydrogels while excessive mixing beyond gel point results in weaker hydrogels due to potential breakage of their 3D network. Furthermore, the hydrogels swell significantly more in cell culture medium than in phosphate-buffered saline, attributed to interactions with additional molecules such as proteins. Thus, moderate mixing gives rise to the most homogenous and mechanically stable hydrogels and the choice of medium e.g., for release experiments, should be consistent in order to avoid unnecessary variations in the data caused by different swelling profiles.

Keywords
Hydrogels, mixing, polymer, rheology, swelling
National Category
Polymer Chemistry
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-158952 (URN)10.1002/mame.201100008 (DOI)000296421800008 ()
Available from: 2011-09-19 Created: 2011-09-19 Last updated: 2017-12-08Bibliographically approved
Ossipov, D. A., Piskounova, S., Varghese, O. P. & Hilborn, J. (2010). Functionalization of Hyaluronic Acid with Chemoselective Groups via a Disulfide-Based Protection Strategy for In Situ Formation of Mechanically Stable Hydrogels. Biomacromolecules, 11(9), 2247-2254
Open this publication in new window or tab >>Functionalization of Hyaluronic Acid with Chemoselective Groups via a Disulfide-Based Protection Strategy for In Situ Formation of Mechanically Stable Hydrogels
2010 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 11, no 9, p. 2247-2254Article in journal (Refereed) Published
Abstract [en]

Functionalization of hyaluronic acid (HA) with chemoselective groups enables in situ (in vivo) formation of HA-based materials in minimally invasive injectable manner. Current methods of HA modification with such groups primarily rely on the use of a large excess of a reagent to introduce a unique reactive handle into HA and, therefore, are difficult to control. We have developed the new protective group strategy based on initial mild cleavage of a disulfide bond followed by elimination of the generated 2-thioethoxycarbonyl moiety ultimately affording free amine-type functionality, such as hydrazide, aminooxy, and carbazate. Specifically, new modifying homobifunctional reagents have been synthesized that contain a new divalent disulfide-based protecting group. Amidation of HA with these reagents gives rise to either one-end coupling product or to intra/intermolecular cross-linking of the HA chains. However, after subsequent treatment of the amidation reaction mixture with dithiothreitol (DTT), these cross-linkages are cleaved, ultimately exposing free amine-type groups. The same methodology was applied to graft serine residues to the HA backbone, which were subsequently oxidized into aldehyde groups. The strategy therefore encompasses a new approach for mild and highly controlled functionalization of HA with both nucleophilic and electrophilic chemoselective functionalities with the emphasis for the subsequent conjugation and in situ cross-linking. A series of new hydrogel materials were prepared by mixing the new HA-aldehyde derivative with different HA-nucleophile counterparts. Rheological properties of the formed hydrogels were determined and related to the structural characteristics of the gel networks. Human dermal fibroblasts remained viable while cultured with the hydrogels for 3 days, with no sign of cytotoxicity, suggesting that the gels described in this study are candidates for use as growth factors delivery vehicles for tissue engineering applications.

National Category
Polymer Chemistry
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-134904 (URN)10.1021/bm1007986 (DOI)000281629600008 ()
Available from: 2010-12-02 Created: 2010-12-02 Last updated: 2017-12-12Bibliographically approved
Organisations

Search in DiVA

Show all publications