| 1. |
- Aldskogius, Håkan, 1943-, et al.
(författare)
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Dorsal Root Injury : A Model for Exploring Pathophysiology and Therapeutic Strategies in Spinal Cord Injury
- 2021
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 10:9
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Forskningsöversikt (refereegranskat)abstract
- Unraveling the cellular and molecular mechanisms of spinal cord injury is fundamental for our possibility to develop successful therapeutic approaches. These approaches need to address the issues of the emergence of a non-permissive environment for axonal growth in the spinal cord, in combination with a failure of injured neurons to mount an effective regeneration program. Experimental in vivo models are of critical importance for exploring the potential clinical relevance of mechanistic findings and therapeutic innovations. However, the highly complex organization of the spinal cord, comprising multiple types of neurons, which form local neural networks, as well as short and long-ranging ascending or descending pathways, complicates detailed dissection of mechanistic processes, as well as identification/verification of therapeutic targets. Inducing different types of dorsal root injury at specific proximo-distal locations provide opportunities to distinguish key components underlying spinal cord regeneration failure. Crushing or cutting the dorsal root allows detailed analysis of the regeneration program of the sensory neurons, as well as of the glial response at the dorsal root-spinal cord interface without direct trauma to the spinal cord. At the same time, a lesion at this interface creates a localized injury of the spinal cord itself, but with an initial neuronal injury affecting only the axons of dorsal root ganglion neurons, and still a glial cell response closely resembling the one seen after direct spinal cord injury. In this review, we provide examples of previous research on dorsal root injury models and how these models can help future exploration of mechanisms and potential therapies for spinal cord injury repair.
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| 2. |
- Han, Yilin, et al.
(författare)
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Effects of microgravity on neural crest stem cells
- 2024
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to microgravity (μg) results in a range of systemic changes in the organism, but may also have beneficial cellular effects. In a previous study we detected increased proliferation capacity and upregulation of genes related to proliferation and survival in boundary cap neural crest stem cells (BC) after MASER14 sounding rocket flight compared to ground-based controls. However, whether these changes were due to μg or hypergravity was not clarified. In the current MASER15 experiment BCs were exposed simultaneously to μg and 1 g conditions provided by an onboard centrifuge. BCs exposed to μg displayed a markedly increased proliferation capacity compared to 1 g on board controls, and genetic analysis of BCs harvested 5 h after flight revealed an upregulation, specifically in μg-exposed BCs, of Zfp462 transcription factor, a key regulator of cell pluripotency and neuronal fate. This was associated with alterations in exosome microRNA content between μg and 1 g exposed MASER15 specimens. Since the specimens from MASER14 were obtained for analysis with 1 week’s delay, we examined whether gene expression and exosome content were different compared to the current MASER15 experiments, in which specimens were harvested 5 h after flight. The overall pattern of gene expression was different and Zfp462 expression was down-regulated in MASER14 BC μg compared to directly harvested specimens (MASER15). MicroRNA exosome content was markedly altered in medium harvested with delay compared to directly collected samples. In conclusion, our analysis indicates that even short exposure to μg alters gene expression, leading to increased BC capacity for proliferation and survival, lasting for a long time after μg exposure. With delayed harvest of specimens, a situation which may occur due to special post-flight circumstances, the exosome microRNA content is modified compared to fast specimen harvest, and the direct effects from μg exposure may be partially attenuated, whereas other effects can last for a long time after return to ground conditions.
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| 3. |
- Han, Yilin, et al.
(författare)
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Molecular genetic analysis of neural stem cells after space flight and simulated microgravity on earth
- 2021
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Ingår i: Biotechnology and Bioengineering. - : John Wiley & Sons. - 0006-3592 .- 1097-0290. ; 118:10, s. 3832-3846
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Tidskriftsartikel (refereegranskat)abstract
- Understanding how stem cells adapt to space flight conditions is fundamental for human space missions and extraterrestrial settlement. We analyzed gene expression in boundary cap neural crest stem cells (BCs), which are attractive for regenerative medicine by their ability to promote proliferation and survival of cocultured and co-implanted cells. BCs were launched to space (space exposed cells) (SEC), onboard sounding rocket MASER 14 as free-floating neurospheres or in a bioprinted scaffold. For comparison, BCs were placed in a random positioning machine (RPM) to simulate microgravity on earth (RPM cells) or were cultured under control conditions in the laboratory. Using next-generation RNA sequencing and data post-processing, we discovered that SEC upregulated genes related to proliferation and survival, whereas RPM cells upregulated genes associated with differentiation and inflammation. Thus, (i) space flight provides unique conditions with distinctly different effects on the properties of BC compared to earth controls, and (ii) the space flight exposure induces postflight properties that reinforce the utility of BC for regenerative medicine and tissue engineering.
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| 4. |
- Omelyanchik, Alexander, et al.
(författare)
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Boosting Magnetoelectric Effect in Polymer-Based Nanocomposites
- 2021
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Ingår i: Nanomaterials. - : MDPI. - 2079-4991. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Polymer-based magnetoelectric composite materials have attracted a lot of attention due to their high potential in various types of applications as magnetic field sensors, energy harvesting, and biomedical devices. Current researches are focused on the increase in the efficiency of magnetoelectric transformation. In this work, a new strategy of arrangement of clusters of magnetic nanoparticles by an external magnetic field in PVDF and PFVD-TrFE matrixes is proposed to increase the voltage coefficient (alpha ME) of the magnetoelectric effect. Another strategy is the use of 3-component composites through the inclusion of piezoelectric BaTiO3 particles. Developed strategies allow us to increase the alpha ME value from similar to 5 mV/cm.Oe for the composite of randomly distributed CoFe2O4 nanoparticles in PVDF matrix to similar to 18.5 mV/cm.Oe for a composite of magnetic particles in PVDF-TrFE matrix with 5%wt of piezoelectric particles. The applicability of such materials as bioactive surface is demonstrated on neural crest stem cell cultures.
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| 5. |
- Trolle, Carl, 1985-, et al.
(författare)
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Boundary cap neural crest stem cells promote angiogenesis after transplantation to avulsed dorsal roots in mice and induce migration of endothelial cells in 3D printed scaffolds
- 2024
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Ingår i: Neuroscience Letters. - : Elsevier. - 0304-3940 .- 1872-7972. ; 826
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Tidskriftsartikel (refereegranskat)abstract
- Dorsal root avulsion injuries lead to loss of sensation and to reorganization of blood vessels (BVs) in the injured area. The inability of injured sensory axons to re-enter the spinal cord results in permanent loss of sensation, and often also leads to the development of neuropathic pain. Approaches that restore connection between peripheral sensory axons and their CNS targets are thus urgently need. Previous research has shown that sensory axons from peripherally grafted human sensory neurons are able to enter the spinal cord by growing along BVs which penetrate the CNS from the spinal cord surface. In this study we analysed the distribution of BVs after avulsion injury and how their pattern is affected by implantation at the injury site of boundary cap neural crest stem cells (bNCSCs), a transient cluster of cells, which are located at the boundary between the spinal cord and peripheral nervous system and assist the growth of sensory axons from periphery into the spinal cord during development. The superficial dorsal spinal cord vasculature was examined using intravital microscopy and intravascular BV labelling. bNCSC transplantation increased vascular volume in a non-dose responsive manner, whereas dorsal root avulsion alone did not decrease the vascular volume. To determine whether bNCSC are endowed with angiogenic properties we prepared 3D printed scaffolds, containing bNCSCs together with rings prepared from mouse aorta. We show that bNCSC do induce migration and assembly of endothelial cells in this system. These findings suggest that bNCSC transplant can promote vascularization in vivo and contribute to BV formation in 3D printed scaffolds.
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