| 1. |
- Edström, Dag, et al.
(författare)
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Integrin α10β1-selected mesenchymal stem cells reduced hypercoagulopathy in a porcine model of acute respiratory distress syndrome
- 2023
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Ingår i: Respiratory Research. - 1465-9921. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stem cells (MSCs) have been studied for their potential benefits in treating acute respiratory distress syndrome (ARDS) and have reported mild effects when trialed within human clinical trials. MSCs have been investigated in preclinical models with efficacy when administered at the time of lung injury. Human integrin α10β1-selected adipose tissue-derived MSCs (integrin α10β1-MSCs) have shown immunomodulatory and regenerative effects in various disease models. We hypothesized that integrin α10β1 selected-MSCs can be used to treat a sepsis-induced ARDS in a porcine model when administering cells after established injury rather than simultaneously. This was hypothesized to reflect a clinical picture of treatment with MSCs in human ARDS. 12 pigs were randomized to the treated or placebo-controlled group prior to the induction of mild to moderate ARDS via lipopolysaccharide administration. The treated group received 5 × 10 6 cells/kg integrin α10β1-selected MSCs and both groups were followed for 12 h. ARDS was confirmed with blood gases and retrospectively with histological changes. After intervention, the treated group showed decreased need for inotropic support, fewer signs of histopathological lung injury including less alveolar wall thickening and reduction of the hypercoagulative disease state. The MSC treatment was not associated with adverse events over the monitoring period. This provides new opportunities to investigate integrin α10β1-selected MSCs as a treatment for a disease which does not yet have any definitive therapeutic options.
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| 2. |
- Gautam, Narinder, et al.
(författare)
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Heparin-binding protein (HBP/CAP37): A missing link in neutrophil-evoked alteration of vascular permeability
- 2001
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 7:10, s. 1123-1127
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphonuclear leukocyte infiltration into tissues in host defense and inflammatory diseasecauses increased vascular permeability and edema formation through unknown mechanisms.Here, we report the involvement of a paracrine mechanism in neutrophil-evoked alteration inendothelial barrier function. We show that upon neutrophil adhesion to the endothelial lining,leukocytic 2 integrin signaling triggers the release of neutrophil-borne heparin-binding protein(HBP), also known as CAP37/azurocidin, a member of the serprocidin family of neutrophilcationic proteins. HBP induced Ca++-dependent cytoskeletal rearrangement and intercellular gapformation in endothelial-cell monolayers in vitro, and increased macromolecular efflux in microvesselsin vivo. Moreover, selective inactivation of HBP prevented the neutrophils from inducingendothelial hyperpermeability. Our data suggest a fundamental role of neutrophil-derivedHBP in the vascular response to neutrophil trafficking in inflammation. Targeting this moleculein inflammatory disease conditions offers a new strategy for prevention of endothelial barrierdysfunction caused by misdirected leukocyte activation.
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| 3. |
- Peterson, Lars, 1936, et al.
(författare)
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Autologous chondrocyte transplantation. Biomechanics and long-term durability.
- 2002
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Ingår i: The American journal of sports medicine. - 0363-5465 .- 1552-3365. ; 30:1, s. 2-12
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the durability of autologous chondrocyte transplantation grafts in 61 patients treated for isolated cartilage defects on the femoral condyle or the patella and followed up for a mean of 7.4 years (range, 5 to 11). Durability was determined by comparing the clinical status at the long-term follow-up with that found 2 years after the transplantation. After 2 years, 50 of the 61 patients had good or excellent clinical results, and 51 of 61 had good or excellent results at 5 to 11 years later. Grafted areas from 11 of the patients were evaluated with an electromechanical indentation probe during a second-look arthroscopy procedure (mean follow-up, 54.3 months; range, 33 to 84); stiffness measurements were 90% or more of those of normal cartilage in eight patients. Eight of twelve 2-mm biopsy samples taken from these patients showed hyaline characteristics with safranin O staining and a homogeneous appearance in polarized light. Three fibrous and eight hyaline biopsy specimens stained positive to aggrecan and to cartilage oligomeric matrix protein. Hyaline-like specimens stained positive for type II collagen, and fibrous, for type I collagen. Autologous chondrocyte transplantation for the treatment of articular cartilage injuries has a durable outcome for as long as 11 years.
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| 4. |
- Thorén, Matilda Munksgaard, et al.
(författare)
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Integrin α10, a novel therapeutic target in glioblastoma, regulates cell migration, proliferation, and survival
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- New, effective treatment strategies for glioblastomas (GBMs), the most malignant and invasive brain tumors in adults, are highly needed. In this study, we investigated the potential of integrin α10Β1 as a therapeutic target in GBMs. Expression levels and the role of integrin α10Β1 were studied in patient-derived GBM tissues and cell lines. The effect of an antibody-drug conjugate (ADC), an integrin a10 antibody conjugated to saporin, on GBM cells and in a xenograft mouse model was studied. We found that integrin α10Β1 was strongly expressed in both GBM tissues and cells, whereas morphologically unaffected brain tissues showed only minor expression. Partial or no overlap was seen with integrins α3, α6, and α7, known to be expressed in GBM. Further analysis of a subpopulation of GBM cells selected for high integrin α10 expression demonstrated increased proliferation and sphere formation. Additionally, siRNA-mediated knockdown of integrin α10 in GBM cells led to decreased migration and increased cell death. Furthermore, the ADC reduced viability and sphere formation of GBM cells and induced cell death both in vitro and in vivo. Our results demonstrate that integrin α10Β1 has a functional role in GBM cells and is a novel, potential therapeutic target for the treatment of GBM.
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