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1.
  • Liljebäck, Hanna, et al. (author)
  • Unsurpassed Intrahepatic Islet Engraftment : the Quest for New Sites for Beta Cell Replacement
  • 2019
  • In: Cell Medicine. - : Sage Publications. - 2155-1790. ; 11
  • Journal article (other academic/artistic)abstract
    • The liver is currently the site of choice for clinical islet transplantation, even though many alternative implantation sites have lately been proposed as more ideal for graft survival. The suggested sites, for example intramuscular space, omentum, bone marrow, and spleen, are sometimes difficult to compare due to differences in animal model, islet isolation procedure, and islet quality. In addition, the variation in transplanted islet mass is vast. The aim of this commentary is to review alternative implantation sites tested experimentally as well as in clinical islet transplantation. Although many sites have been investigated, none have convincingly proved better suited for clinical islet transplantation than intraportal injection to the liver, regardless of whether it is autologous or allogeneic transplantation. However, in order to fully evaluate upcoming bioengineering techniques, such as scaffolds containing insulin-producing cells derived from stem cells, the need of an alternative site has arisen to enable cellular monitoring, which currently cannot be achieved within the liver.
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2.
  • McGrath, Aleksandra M., et al. (author)
  • Long-Term Effects of Fibrin Conduit with Human Mesenchymal Stem Cells and Immunosuppression after Peripheral Nerve Repair in a Xenogenic Model
  • 2018
  • In: Cell Medicine. - : SAGE Publications. - 2155-1790. ; 10, s. 1-13
  • Journal article (peer-reviewed)abstract
    • Introduction: Previously we showed that a fibrin glue conduit with human mesenchymal stem cells (hMSCs) and cyclosporine A (CsA) enhanced early nerve regeneration. In this study long term effects of this conduit are investigated. Methods: In a rat model, the sciatic nerve was repaired with fibrin conduit containing fibrin matrix, fibrin conduit containing fibrin matrix with CsA treatment and fibrin conduit containing fibrin matrix with hMSCs and CsA treatment, and also with nerve graft as control. Results: At 12 weeks 34% of motoneurons of the control group regenerated axons through the fibrin conduit. CsA treatment alone or with hMSCs resulted in axon regeneration of 67% and 64% motoneurons respectively. The gastrocnemius muscle weight was reduced in the conduit with fibrin matrix. The treatment with CsA or CsA with hMSCs induced recovery of the muscle weight and size of fast type fibers towards the levels of the nerve graft group. Discussion: The transplantation of hMSCs for peripheral nerve injury should be optimized to demonstrate their beneficial effects. The CsA may have its own effect on nerve regeneration.
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3.
  • Molnar, Matyas, et al. (author)
  • Effects of Quantum Dot Labeling on Endothelial Progenitor Cell Function and Viability
  • 2010
  • In: Cell Medicine. ; 1:2, s. 105-112
  • Journal article (peer-reviewed)abstract
    • Endothelial progenitor cells (EPC) play an important role in repairing damaged endothelium. An effective imaging method for in vivo tracking of EPCs is essential for understanding EPC-based cell therapy. Fluorescent quantum dots (QDs) have attractive optical characteristics such as extreme brightness and photostability. QDs are currently being investigated as probes for stem cell labeling; however, there is concern about whether QDs can be used safely. We investigated whether quantum dot (QD) labeling would influence EPC viability and function. Rat bone marrow-derived EPCs were cultured and characterized. The cells were labeled with near-infrared-emitting, carboxyl-coated QDs (8 nM) for 24 h. QD labeling efficiency was higher than 97%. Using WST-1 assay, we showed that the viability of the QD-labeled EPCs was not different from that of the control EPCs. Moreover, QD labeling did not influence the ability of EPCs to form capillary tubes on Matrigel and to migrate. The percentage of QD-positive cells decreased with time, probably due to the rapid division of EPCs. These data suggest that the carboxyl-coated QD705 can be useful for labeling EPCs without interrupting their viability and functions.
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4.
  • Schive, Simen W., et al. (author)
  • Human Adipose-Derived Mesenchymal Stem Cells Respond to Short-Term Hypoxia by Secreting Factors Beneficial for Human Islets In Vitro and Potentiate Antidiabetic Effect In Vivo
  • 2017
  • In: Cell Medicine. - 2155-1790. ; 9:3, s. 103-116
  • Journal article (peer-reviewed)abstract
    • Adipose-derived mesenchymal stem cells (ASCs) release factors beneficial for islets in vitro and protect against hyperglycemia in rodent models of diabetes. Oxygen tension has been shown to induce metabolic changes and alter ASCs' release of soluble factors. The effects of hypoxia on the antidiabetic properties of ASCs have not been explored. To investigate this, we incubated human ASCs for 48 h in 21% (normoxia) or 1% O-2 (hypoxia) and compared viability, cell growth, surface markers, differentiation capability, and soluble factors in the conditioned media (CM). Human islets were exposed to CM from ASCs incubated in either normoxia or hypoxia, and islet function and apoptosis after culture with or without proinflammatory cytokines were measured. To test hypoxic preconditioned ASCs' islet protective effects in vivo, ASCs were incubated for 48 h in normoxia or hypoxia before being injected into Balb/c Rag 1(-/-) immunodeficient mice with streptozotocin-induced insulitis. Progression of diabetes and insulin content of pancreas were measured. We found that incubation in hypoxia was well tolerated by ASCs and that levels of VEGF-A, FGF-2, and bNGF were elevated in CM from ASCs incubated in hypoxia compared to normoxia. while levels of HGF, IL-8, and CXCL1 were reduced. CM from ASCs incubated in hypoxia significantly improved human islet function and reduced apoptosis after culture, and reduced cytokine-induced apoptosis. In our mouse model, pancreas insulin content was higher in both groups receiving ASCs compared to control, but the mice receiving preconditioned ASCs had lower random and fasting blood glucose, as well as improved oral glucose tolerance compared to untreated mice. In conclusion, our in vitro results indicate that the islet protective potential of ASCs improves in hypoxia, and we give insight into factors involved in this. Finally we show that hypoxic preconditioning potentiates ASCs' anti-diabetic effect in vivo.
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