Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Boundary cap neural crest stem cells homotopically implanted to the injured dorsal root transitional zone give rise to different types of neurons and glia in adult rodents
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
Show others and affiliations
2014 (English)In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 15, 60- p.Article in journal (Refereed) Published
Abstract [en]

The boundary cap is a transient group of neural crest-derived cells located at the presumptive dorsal root transitional zone (DRTZ) when sensory axons enter the spinal cord during development. Later, these cells migrate to dorsal root ganglia and differentiate into subtypes of sensory neurons and glia. After birth when the DRTZ is established, sensory axons are no longer able to enter the spinal cord. Here we explored the fate of mouse bNCSCs implanted to the uninjured DRTZ after dorsal root avulsion for their potential to assist sensory axon regeneration. Grafted cells showed extensive survival and differentiation after transplantation to the avulsed DRTZ. Transplanted cells located outside the spinal cord organized elongated tubes of Sox2/GFAP expressing cells closely associated with regenerating sensory axons or appeared as small clusters on the surface of the spinal cord. Others, migrating into the host spinal cordas single cells, differentiated to spinal cord neurons with different neurotransmitter characteristics, extensive fiber organization, and in some cases surrounded by glutamatergic terminal-like profiles. These findings demonstrate that bNCSCs implanted at the site of dorsal root avulsion injury display remarkable differentiation plasticity inside the spinal cord and in the peripheral compartment where they organize tubes associated with regenerating sensory fibers. These properties offer a basis for exploring the ability of bNCSCs to assist regeneration of sensory axons into the spinal cord and replace lost neurons in the injured spinal cord.

Place, publisher, year, edition, pages
BioMed Central, 2014. Vol. 15, 60- p.
Keyword [en]
neural stem cell, sensory neuron, spinal cord injury, cell differentiation, nerve regeneration, cell replacement
National Category
Neurosciences Neurology
Research subject
Neuroscience
Identifiers
URN: urn:nbn:se:uu:diva-218685DOI: 10.1186/1471-2202-15-60ISI: 000337318200001OAI: oai:DiVA.org:uu-218685DiVA: diva2:696530
Funder
Swedish Research Council, 20716Swedish Research Council, 5420
Available from: 2014-02-14 Created: 2014-02-14 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Stem Cell Transplantation in Dorsal Root Injury
Open this publication in new window or tab >>Stem Cell Transplantation in Dorsal Root Injury
2014 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

After traumatic injuries to the brachial plexus there is a risk that one or more of the spinal roots are torn from the spinal cord, known as avulsion injury. This often leads to paralysis and chronic pain, notoriously difficult to treat with current pharmacotherapy. Surgical treatment may improve motor function but sensory recovery is usually poor as sensory axons fail to establish functional connections inside the spinal cord. The aims of this thesis were to develop a model for dorsal root avulsion in rodents in order to investigate the potentials of stem cell therapy for enhancing sensory regeneration after spinal root avulsion. Two different types of stem cells, embryonic and neural crest stem cells, have been transplanted to the avulsion model and analysed using immunohistochemical methods. The results indicate that stem cells survive after transplantation to the avulsed dorsal root and associate with regenerating axons. Furthermore, the different stem cells display different phenotypes after transplantation where embryonic stem cells give rise to neurons located outside the spinal cord that could serve as projection neurons whereas the neural crest stem cells form elongated tubes outlining the avulsed dorsal root and are associated with regenerating neuronal fibers. We have also discovered that the neural crest stem cells migrate into the damaged spinal cord as single cells. The neural crest stem cells also display a diversity in generating both neuronal and glial cells that may have different beneficial effects in neural repair following dorsal root avulsion. To improve the survival of stem cell transplants, the potentials of co-transplanting embryonic stem cells together with nanoparticle delivered growth factor mimetics has been investigated. The results indicate that nanoparticle delivered growth factors improve both transplant survival and maturation in comparison to untreated controls and may be a promising strategy in stem cell transplantation.

Place, publisher, year, edition, pages
Uppsala: Institutionen för neurovetenskap, 2014. x+46 p.
Keyword
Sensory Neuron, Regeneration, Spinal Root, Stem Cell
National Category
Neurosciences
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-218686 (URN)
Presentation
2014-03-18, BMC A7:115, Husargatan 3, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2014-02-26 Created: 2014-02-14 Last updated: 2014-03-20Bibliographically approved
2. 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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1105
Keyword
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
Identifiers
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)
Opponent
Supervisors
Available from: 2015-05-18 Created: 2015-04-20 Last updated: 2015-07-07
3. Stem cell transplantation and regeneration after dorsal root avulsion
Open this publication in new window or tab >>Stem cell transplantation and regeneration after dorsal root avulsion
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Spinal root avulsion leads to paralysis and loss of sensory function. Surgical methods can improve motor function and ameliorate pain but sensory recovery in adults is poor. Previous studies have shown that cell transplantation or treatment with trophic factors can improve functional outcome in rodents after dorsal root transection or crush. Here, a dorsal root injury model, more similar to human avulsion injuries, was used. The aims of this thesis were to investigate the behaviour of different stem cells following transplantation to avulsed dorsal roots and asses their potential to serve as possible regenerative therapy. In paper I, different murine stem cell types were transplanted to avulsed dorsal roots in rats. Murine embryonic stem cells remained outside the spinal cord and were surrounded by glutamatergic terminals. Boundary cap neural crest stem cells (bNCSC) formed elongated bands outside the spinal cord and migrated to the spinal cord as single cells. In paper II, transplanted bNCSC were further characterized. bNCSC remaining outside the spinal cord expressed glial markers and were associated with different types of sensory fibres. bNCSC that migrated into the injured spinal cord expressed different neuronal markers. In paper III, effects of bNCSC transplantation on local vasculature and glial scar formation were studied. bNCSC increase angiogenesis in a non dose response manner and participate in boundary glial scar formation. In paper IV, bNCSC spinal migration was analysed using two different injury models - dorsal root transection and dorsal root avulsion. In addition, bNCSC capacity to support sensory regeneration was assessed and the results suggest that bNCSC do not support robust regeneration of avulsed afferents. In paper V, an in vitro stem cell model system was used to assess the possibility of using artificial nanomaterials to deliver differentiation factors. Cells treated with either soluble factors or particle-delivered factors showed similar differentiation patterns. Stem cell transplantation offers several opportunities following dorsal root avulsion, including cell replacement and regenerative support. By elucidating the mechanisms by which stem cells can assist regeneration of avulsed afferents will allow for more targeted or combinatorial approaches, including growth factor treatment.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 62 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1162
Keyword
Regeneration, dorsal root, sensory nerve, nerve injury, cell transplantation
National Category
Neurosciences
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-265853 (URN)978-91-554-9410-0 (ISBN)
Public defence
2016-01-08, B/C2:301, BMC, Husargatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2015-12-17 Created: 2015-11-03 Last updated: 2016-01-27

Open Access in DiVA

fulltext(3402 kB)208 downloads
File information
File name FULLTEXT01.pdfFile size 3402 kBChecksum SHA-512
75f902c9aa9ece061b70d5396c183078835f1ef8965a77f3105e14239127313975c0706b0cb806b76c7be05152a4621bb69c496802c37b4fb01790fad6e169a8
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Trolle, CarlAbrahamsson, NinnieKönig, NiclasVasylovska, SvitlanaKozlova, Elena
By organisation
Regenerative neurobiology
In the same journal
BMC neuroscience (Online)
NeurosciencesNeurology

Search outside of DiVA

GoogleGoogle Scholar
Total: 208 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 703 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf