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- Brohlin, Maria
(författare)
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Mesenchymal stem cells for repair of the peripheral and central nervous system
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bone marrow-derived mesenchymal stem cells (MSC) have been shown to provide neuroprotection after transplantation into the injured nervous system. The present thesis investigates whether adult human and rat MSC differentiated along a Schwann cell lineage could increase their expression of neurotrophic factors and promote regeneration after transplantation into the injured peripheral nerve and spinal cord. Human and rat mesenchymal stem cells (hMSC and rMSC) expressed characteristic stem cell surface markers, mRNA transcripts for different neurotrophic factors and demonstrated multi-lineage differentiation potential. Following treatment with a cocktail of growth factors, the hMSC and rMSC expressed typical Schwann cells markers at both the transcriptional and translational level and significantly increased production of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). Age and time in culture are of relevance for clinical settings and growth-promoting effects of hMSC from young donors (16-18 years) and old donors (67-75 years) were compared. Undifferentiated hMSC from both young and old donors increased total neurite length of cultured dorsal root ganglion (DRG) neurons. Differentiation of hMSC from the young donors, but not the eldery donors, further enhanced the neurite outgrowth. Undifferentiated hMSC were cultured for eleven weeks in order to examine the effect of in vitro expansion time on neurite outgrowth. hMSC from the young donors maintained their proliferation rate and their ability to enhance neurite outgrowth from DRG neurons. Using a sciatic nerve injury model, a 10mm gap was bridged with either an empty tubular fibrin glue conduit, or conduits containing hMSC, with and without cyclosporine treatment. Cells were labeled with PKH26 prior to transplantation. At 3 weeks after injury the conduits with cells and immunosuppression increased regeneration compared with an empty conduit. PKH26 labeled human cells survived in the rat model and the inflammatory reaction could be suppressed by cyclosporine. After cervical C4 hemisection, BrdU/GFP-labeled rMSC were injected into the lateral funiculus rostral and caudal to the spinal cord lesion site. Spinal cords were analyzed 2-8 weeks after transplantation. Transplanted MSC remained at the injection sites and in the trauma zone for several weeks and were often associated with numerous neurofilament-positive axons. Transplanted rMSC induced up-regulation of vascular endothelial growth factor in spinal cord tissue rostral to the injury site, but did not affect expression of brain-derived neurotrophic factor. Although rMSC provided neuroprotection for rubrospinal neurons and significantly attenuated astroglial and microglial reaction, cell transplantation caused aberrant sprouting of calcitonin gene-related peptide immunostained sensory axons in the dorsal horn. In summary these results demonstrate that both rat and human MSC can be differentiated towards the glial cell lineage, and show functional characteristics similar to Schwann cells. hMSC from the young donors represent a more favorable source for neurotransplantation since they maintain proliferation rate and preserve their growth-promoting effects in long-term cultures. The data also suggest that differentiated MSC increase expression of neurotrophic factors and support regeneration after peripheral nerve and spinal cord injury.
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- Kristoffersen Wiberg, Maria
(författare)
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Magnetic resonance imaging in breast diagnosis
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- MRI of the breast has, since the introduction of gadolinium contrast agents, been increasingly used in breast investigations. MRI has been found to have a high sensitivity but a low specificity in cancer detection. The aim of this thesis was to study and establish the role of MRI in the clinical diagnosis of breast lesions. Which kind of lesions and which patients would benefit the most from MRI of the breast as an adjunct to other breast imaging modalities, and how should MRI be used in a clinical setting? In study I a comparison of the appearance of 27 lesions in two different T1-weighted 3D sequences regarding the contrast inherent in the sequences and following contrast enhancement was performed. Due to strong and widespread enhancement on the routine FLASH-sequence these lesions were examined with another T1-weighted sequence. The FLASH-sequence was found to have a high sensitivity, revealing contrast-enhancing areas, and therefore remains the first choice for routine examinations. The MPRAGE-sequence was found to increase the specificity by downgrading false positive lesions to true negatives. In study II the histological changes caused by fine needle aspiration biopsy (FNAB) that theoretically might affect the evaluation of breast lesions on semidynamic MRI was evaluated in 17 lesions. According to our result MRI can be performed irrespective of the time interval to a performed FNAB, as the evaluations were not impaired. In study III dynamic contrast enhanced MRI (CE-MRI) was found to be a valuable adjunctive method to clinical examination, mammography and FNAB (triple diagnosis,TD) due to high sensitivity, but at the cost of a decreased specificity. This decrease was less pronounced in mammographically dense breasts, and hence these patients might benefit most from CE-MRI as an adjunctive investigation. In study IV lesion size at CE-MRI and mammography were compared to histopathological size. The size of a breast cancer is of importance in the choice of treatment, in particular when breast-conserving surgery is considered. CE-MRI and mammography were both good at measuring the size of detected invasive breast malignancies. The total sizes of malignant lesions were frequently underestimated by both methods. In study V the diagnostic accuracy of CE-MRI and scinti-mammography was compared, and the clinical value as an adjunct to mammography was evaluated. Dynamic CE-MRI and 99mTc-sestamibi scinti-mammography showed comparable diagnostic accuracy, but a better accuracy was found for the combination of CE-MRI and mammography when using ROC curves for evaluation. In lesions smaller than 10 mm in size 99mTc-sestamibi scinti-mammography was found to be less reliable due to the low spatial resolution. In conclusion, MRI is a useful tool in breast diagnosis, in particular due to its high sensitivity, the ability to exclude multifocality/multicentricity and accuracy in determining size and extent of a lesion. Due to the low specificity MRI is not to be recommended as a general screening tool, but as an adjunctive method in selected cases.
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- Lauvrud, Anne Therese, 1975-
(författare)
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Optimizing stem cells for reconstructive surgery
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fat grafting has become an established method in plastic surgery for treating soft tissue defects. The results for survival of the fat being transplanted is unpredictable and supplementation of the graft with the Stromal Vascular Fraction (SVF) or cultures Adipose tissue-derived stem cells (ASCs) can enhance graft viability. The ASCs are a heterogenous group of cells with various cell membrane markers, and differing growth promoting and differentiation characteristics of the stem cells derived from the fat. It is of high importance when expanding cells prior to the transplantation of the cells into patients, that the culture conditions are well defined and ideally are xenofree, avoiding use of animal-derived products. Furthermore, the procedures must be safe and not increase risk for recurrence of cancer after reconstructive surgeries. This thesis explores the phenotypic properties of a selected population of ASCs, with a view to determining their suitability for transplantation into fat grafts. ASCs were isolated from SVF of human abdominal fat and CD146+ cells were selected using immunomagnetic beads. The proliferation, angiogenic and adipogenic properties were significantly higher in the CD146+ cells. Stem cells were also isolated from lipoaspirate obtained using two different liposuction methods. Waterjet lipoaspirates yielded the greatest number of CD146+ cells with high adipogenic potential and angiogenic activity. The cells could also be successfully isolated using a closed processing system. Cells were expanded in either foetal bovine serum, platelet lysate or a chemically defined xenofree (XV) medium. Cultures in XV medium proliferated the fastest, expressed the highest number of CD146+ cells, and showed the best adipogenic and angiogenic properties. To test possible ASCs interactions with cancer cells, co-cultures with MCF-7 breast cancer cells were established. Conditioned medium from co-cultures significantly increased the migration of the cancer cells but not their proliferation, and there was increased expression of Tenascin-C in these cultures. The research in this thesis work has shown more optimal ways to isolate and expand ASCs, potentially offering new therapeutic reconstructive treatment options for a variety of medical conditions.
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- Mantovani, Maria Cristina, 1974-
(författare)
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Schwann cells and mesenchymal stem cells as promoter of peripheral nerve regeneration
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The transplantation of primary Schwann cells (SC) has been shown to improve nerve regeneration. However, to monitor the survival of transplanted cells within the host, a stable labelling method is required. The in vitro characteristics of green fluorescent protein labelled SC (GFP SC) and their effects in an in vivo peripheral nerve injury model were investigated. The GFP-SC were readily visualised ex vivo and stimulated significantly better axonal regeneration compared to controls. Clinical use of autologous SC for the treatment of nerve injuries is of limited use due to difficulty in obtaining clinically useful numbers. However, bone marrow mesenchymal stem cells (MSC) can trans-differentiate into SC like cells (dMSC). The in vitro and in vivo differentiation of MSC was explored, and the study extended to include the easily-accessible adipose stem cells (ASC). In vitro, glial growth factor stimulated MSC express S100, a SC marker, and its expression is maintained following in vivo transplantation. Similarly, untreated MSC transplanted in vivo also expressed S100, which indicates glial differentiation in response to local cytokines and growth factors. Using an in vitro model, comprising dMSC or dASC co-cultured with adult dorsal root ganglia (DRG) neurons, the capacity of the dMSC and SC like differentiated ASC (dASC) to promote axon myelination was verified: both cell types expressed transcripts for protein zero, peripheral myelin protein-22 and myelin basic protein.The potential of stem cells in nerve repair may be limited by innate cellular senescence or donor age affecting cell functionality thus it was essential to determine the effects of donor age on morphology and functionality of stem cells. The proliferation rates, expression of senescence markers (p38 and p53) and the stimulation of neurite outgrowth from DRG neurons by stem cells isolated from neonatal, young or old rats were very similar. However, the distribution and ultrastructure of mitochondria in dMSC and dASC from young and old rats were quite different, and seem to indicate physiological senescence of the aged cells. Given the wide-ranging influence of Notch signalling in cell differentiation, including the neural crest to a glial cell type switch, and self-renewal in mammals, its role in the differentiation of stem cells to SC was investigated. The mRNA for notch-1 and -2 receptors were expressed in the dASC, blockage of notch signaling did not affect the neurotrophic and myelination potential of dASC. In conclusion, these findings show that GFP labelling has no deleterious effect on SC survival and function. MSC and ASC differentiated into glial-type cells acquire SC morphology, and express characteristic SC markers, and the differentiation process was independent of the Notch signaling pathway. Also, following transplantation into a nerve gap injury dMSC improve regeneration. This study established that following co-culture with DRG neurons, dMSC and dASC were able to express peripheral myelin proteins. Also, the functional bioactivity of these cells is independent of the donor animal age. Finally, although the glial lineage differentiated aged cells characterized in this study expressed markers typical of senescence they retained the potential to support axon regeneration.
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- McGrath, Aleksandra, et al.
(författare)
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Fibrin conduit supplemented with human mesenchymal stem cells supports regeneration after peripheral nerve injury
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- To address the need for the development of bioengineered replacement of a nerve graft for treatment of peripheral nerve injuries a novel two component fibrin glue conduit was combined with human mesenchymal stem cells (hMSC) and immunosupressive treatment with cyclosporine. MSC possess the advantage of lower donor site morbidity and easier expandability in vitro compared with Schwann cells. The effects of hMSC on axonal regeneration in the conduit and reaction of activated macrophages was investigated using sciatic nerve injury model. The experiments were performed on 20 female Fischer rats (8-10 weeks old). A 10mm gap in the sciatic nerve was created and repaired either with fibrin glue conduit containing diluted fibrin matrix or fibrin glue conduit containing fibrin matrix with hMSC at concentration of 80x106 cells per ml. Cells were labeled with PKH26 prior to transplantation. The animals were allowed to survive for 3 weeks and some groups were treated with daily injections of cyclosporine. After 3 weeks the conduits were harvested and the distance of regeneration and area occupied by regenerating axons together with ED1 staining of activated macrophages was measured. hMSC survived in the conduit and enhanced axonal regeneration only when transplantation was combined with cyclosporine treatment. Moreover, cyclosporine significantly reduced the ED1 macrophage reaction.
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- Pettersson, Karin, 1972, et al.
(författare)
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Metoder och verktyg för utvärdering av kursinslag i informationskompetens
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet har varit att skapa en verktygslåda med förslag på metoder och verktyg att använda vid utvärdering av kursinslag inom området informationskompetens, av relevans för högskole- och gymnasiebibliotek. Projektet har haft tre faser. I den första gjordes en litteraturgenomgång av internationell forskningslitteratur kring utvärdering. Litteraturstudien mynnade ut i en sammanställning av metoder och verktyg för utvärdering av kursinslag i informationskompetens. I fas två testades ett urval av de sammanställda utvärderingsverktygen på biblioteken i Göteborg, Lund och Mölnlycke. Resultaten från testerna integrerades med sammanställningen från litteraturstudien till det som är projektets huvudresultat, verktygslådan. Projektets tredje fas är spridning av resultaten i form av verktygslådan.
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- Poikolainen Rosén, Anton, 1992-
(författare)
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Noticing nature : exploring more-than-human-centred design in urban farming
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis articulates, theorises and furthers the concept of “more-than-human-centred design” by studying the use and design of technology for noticing nature and caring for nature. The emerging field of more-than-human-centred design focuses on the mutual interdependence between humans and non-humans (e.g. organisms such as animals, plants and microbes, as well as autonomous technologies). It is a step away from seeing other organisms as inferior to humans or valuable only as resources. This implies that design research frameworks and methods need to be remade. How can we design for and with other organisms? What needs to be accommodated in a paradigm that allows for more-than-human-centred design? What are concrete design examples and implications of this kind of thinking? In short, there is a need to investigate what it means to design for more-than-human worlds.This is investigated in the thesis through a series of studies and design experiments, including ethnography (participant observation, interviews, surveys and workshops), design projects (design ideation, development and analysis of prototypes) and design critique of existing artefacts. Most of these studies are conducted within a four-year ethnography of a regenerative urban farming community in Stockholm, Sweden.The thesis draws on posthuman theory. This theory examines the implications of expanding concern and subjectivities beyond the human, and aims to understand the human subject and its relationship to the world in a non-anthropocentric light. Phenomenological analysis is further applied to articulate and understand the human-technology-nature relationship as it is experienced first-person.The thesis contributes an articulation of a more-than-human-centred design programme. Here, two design implications are suggested, “expanding the sensible” and “design for sensory-rich experiences”. Methods for noticing the more-than-human world are suggested, along with principles for designing for and with other organisms, such as finding leverage points in systems and providing a scaffold for naturally occurring processes. The meaning of “design”, “the designer” and “the user” is discussed. Lastly, a manifesto for more-than-human-centred design is proposed.
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