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Human spinal cord neural progenitors alone but not in combination with growth factor mimetic loaded mesoporous silica assist regeneration of sensory fibers into the spinal cord after dorsal root avulsion
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Elena Kozlova, Regenerative Medicine)
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Spinal root avulsion injuries result in permanent loss of sensory function and often cause neuropathic pain. We recently showed that human embryonic stem cells derived neural progenitors (hNP) transplanted to the site of avulsed dorsal roots assist regeneration of sensory fibers into the adult mouse spinal cord. Here, we explored the potential of human spinal cord neural stem/progenitor cells (hscNSPCs) and of growth factor mimetics loaded nanoparticles to repair spinal root avulsion injury. We found that hscNSPCs and to some extent mimetic loaded nanoparticles support regeneration of sensory axons into the spinal cord when they are applied separately, whereas hscNSPCs implanted together with mimetic-loaded nanoparticles failed to support sensory  regeneration. These findings suggest that the positive effect of hscNSPCs may be eliminated by nanoparticle mediated release of neurotrophic factors due to changes in stem cell properties or surrounding cells at the place of avulsion, preventing growth of injured sensory axons into the spinal cord. Thus, hscNSPCs are able to assist restoration of sensory connections between the PNS and spinal cord, although not in combination with nanoparticle-delivered neurotrophic factor mimetics.

National Category
URN: urn:nbn:se:uu:diva-251490OAI: oai:DiVA.org:uu-251490DiVA: diva2:806355
Swedish Research Council, 20716
Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2015-07-07
In thesis
1. Reconnecting the CNS and PNS with Stem Cell Transplantation
Open this publication in new window or tab >>Reconnecting the CNS and PNS with Stem Cell Transplantation
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Severe injury may result in disconnection between the peripheral and central nervous system. Regeneration of the central portion of sensory neurons into the spinal cord is notoriously poor in adult mammals, with low regenerative drive and an unpermissive central environment, most likely resulting in persistent loss of sensory function. A variety of strategies have been addressedto augment regeneration, including application of growth promoting factors, counteraction of inhibitory molecules, and provision of growth permissive substrates. Stem cells have been investigated in these contexts, as well as for the possibility of providing new neurons to act as a relay between the periphery and spinal cord. Here we have investigated different sources of neural stem cells for their ability to form neurons and glia after transplantation to the periphery; to project axons into the spinal cord; and to assist regeneration of surviving sensory neurons. These have been performed at two locations: the "dorsal root ganglion cavity", and the transitional zone following dorsal root avulsion. Neurons and glia were generated form mouse boundary cap neural crest stem cells and embryonic stem cell derived ventral spinal cord progenitors, and in addition to this, regeneration of sensory fibers was observed after transplantation of human fetal spinal cord derived progenitors and human embryonic stem cell derived ventral spinal cord progenitors. Further, delivery of neurotrophic factor mimetics via mesoporous silica nanoparticles proved a valuable tool for stem cell survival and differentiation. While technological advances make in vivo differentiation a realistic goal, our findings indicate that so far assisting regeneration of host sensory fibers to reconnect with the spinal cord by transplantation of stem cells is a more reliable strategy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 54 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1105
stem cell transplantation, regenerative neurobiology, nerve injury repair
National Category
Neurosciences Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Medical Science
urn:nbn:se:uu:diva-251546 (URN)978-91-554-9252-6 (ISBN)
Public defence
2015-06-08, B/C2:301, BMC, Husargatan 3, Uppsala, 10:00 (English)
Available from: 2015-05-18 Created: 2015-04-20 Last updated: 2015-07-07

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König, Niclas
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