uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • 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
Stem Cell Transplantation in Dorsal Root Injury
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
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 [sv]
Sensory Neuron, Regeneration, Spinal Root, Stem Cell
National Category
Neurosciences
Research subject
Neuroscience
Identifiers
URN: urn:nbn:se:uu:diva-218686OAI: oai:DiVA.org:uu-218686DiVA: diva2:696547
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
List of papers
1. Murine neural crest stem cells and embryonic stem cell derived neuron precursors survive and differentiate after transplantation in a model of dorsal root avulsion
Open this publication in new window or tab >>Murine neural crest stem cells and embryonic stem cell derived neuron precursors survive and differentiate after transplantation in a model of dorsal root avulsion
Show others...
2017 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 11, no 1, 129-137 p.Article in journal (Refereed) Published
Abstract [en]

Spinal root avulsion results in paralysis and sensory loss, and is commonly associated with chronic pain. In addition to the failure of avulsed dorsal root axons to regenerate into the spinal cord, avulsion injury leads to extensive neuroinflammation and degeneration of second order neurons in the dorsal horn. The ultimate objective with the treatment of this condition is to counteract degeneration of spinal cord neurons and to achieve functionally useful regeneration/reconnection of sensory neurons with spinal cord neurons. Here we explore if stem cells transplanted on the surface of avulsed spinal cord can survive, differentiate and migrate into the damaged spinal cord during the first few weeks after this intervention. Murine boundary cap neural crest stem cells (bNCSCs) or embryonic stem cell (ESC)-derived, pre-differentiated neuron precursors were implanted acutely at the junction between avulsed dorsal roots L3-L6 and the spinal cord. Both types of cells survived transplantation, but showed distinctly different modes of differentiation. Thus, bNCSCs migrated into the spinal cord, expressed glial markers, and formed elongated tubes in the peripheral nervous system (PNS) compartment of the avulsed dorsal root transitional zone(DRTZ) area. In contrast, the ESC-transplants remained at the site of implantation and differentiated to motor neurons and interneurons. These data show that both stem cell types successfully survive implantation to the acutely injured spinal cord and maintained their differentiation and migration potential. These data suggest that depending on the source of neural stem cells, they can play different beneficial roles for recovery after dorsal root avulsion.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keyword
sensory neuron, spinal cord, dorsal root transitional zone, regeneration, migration, glial cells, Schwann cells, motor neurons
National Category
Neurosciences
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-218684 (URN)10.1002/term.1893 (DOI)000394173600012 ()24753366 (PubMedID)
Funder
Swedish Research Council, 20716
Available from: 2014-02-14 Created: 2014-02-14 Last updated: 2017-12-06Bibliographically approved
2. 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
Open this publication in new window or tab >>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
Show others...
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
Keyword
neural stem cell, sensory neuron, spinal cord injury, cell differentiation, nerve regeneration, cell replacement
National Category
Neurosciences Neurology
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-218685 (URN)10.1186/1471-2202-15-60 (DOI)000337318200001 ()
Funder
Swedish Research Council, 20716Swedish Research Council, 5420
Available from: 2014-02-14 Created: 2014-02-14 Last updated: 2017-12-06Bibliographically approved
3. Delivery of Differentiation Factors by Mesoporous Silica Particles Assists Advanced Differentiation of Transplanted Murine Embryonic Stem Cells
Open this publication in new window or tab >>Delivery of Differentiation Factors by Mesoporous Silica Particles Assists Advanced Differentiation of Transplanted Murine Embryonic Stem Cells
Show others...
2013 (English)In: Stem Cells Translational Medicine, ISSN 2157-6564, E-ISSN 2157-6580, Vol. 2, no 11, 906-915 p.Article in journal (Refereed) Published
Abstract [en]

Stem cell transplantation holds great hope for the replacement of damaged cells in the nervous system. However, poor long-term survival after transplantation and insufficiently robust differentiation of stem cells into specialized cell types in vivo remain major obstacles for clinical application. Here, we report the development of a novel technological approach for the local delivery of exogenous trophic factor mimetics to transplanted cells using specifically designed silica nanoporous particles. We demonstrated that delivering Cintrofin and Gliafin, established peptide mimetics of the ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, respectively, with these particles enabled not only robust functional differentiation of motor neurons from transplanted embryonic stem cells but also their long-term survival in vivo. We propose that the delivery of growth factors by mesoporous nanoparticles is a potentially versatile and widely applicable strategy for efficient differentiation and functional integration of stem cell derivatives upon transplantation.

Keyword
Cell transplantation, Differentiation, Embryonic stem cells, Nervous system, Neural differentiation, Neural stem cell, Stem cell culture, Transplantation
National Category
Natural Sciences Engineering and Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-211443 (URN)10.5966/sctm.2013-0072 (DOI)000326312000017 ()
Note

De 3 första författarna delar förstaförfattarskapet

Available from: 2013-11-27 Created: 2013-11-25 Last updated: 2017-12-06Bibliographically approved

Open Access in DiVA

fulltext(6981 kB)1052 downloads
File information
File name FULLTEXT01.pdfFile size 6981 kBChecksum SHA-512
6eaa8dc7f791c034aabebf33e7945c6b4e81863c79f0c01d543a3276061a8d9624565544bfb8a3bb85026f82f95c0746a8757ec5d973ea82e594a9c9acc4a347
Type fulltextMimetype application/pdf
errata(74 kB)157 downloads
File information
File name ERRATA01.pdfFile size 74 kBChecksum SHA-512
cf8c3ed28a40d170b1f079086452e2967435cdef98972f61f3597d12e69ac236e339b611ff58fe0aa3733e173dbb39f902b1ee7ca6e9b3bc015457a687f5cd0d
Type errataMimetype application/pdf

Authority records BETA

Trolle, Carl

Search in DiVA

By author/editor
Trolle, Carl
By organisation
Department of Neuroscience
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 1052 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

urn-nbn

Altmetric score

urn-nbn
Total: 954 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • 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