Logo: to the web site of Uppsala University

uu.sePublikasjoner fra Uppsala universitet
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Forced Runx1 expression in human neural stem/progenitor cells transplanted to the rat dorsal root ganglion cavity results in extensive axonal growth specifically from spinal cord-derived neurospheres
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuroanatomi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuroanatomi.
Vise andre og tillknytning
2011 (engelsk)Inngår i: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 20, nr 11, s. 1847-1857Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Cell replacement therapy holds great promise for treating a wide range of human disorders. However, ensuring the predictable differentiation of transplanted stem cells, eliminating their risk of tumor formation, and generating fully functional cells after transplantation remain major challenges in regenerative medicine. Here, we explore the potential of human neural stem/progenitor cells isolated from the embryonic forebrain (hfNSPCs) or the spinal cord (hscNSPCs) to differentiate to projection neurons when transplanted into the dorsal root ganglion cavity of adult recipient rats. To stimulate axonal growth, we transfected hfNSPC- and hscNSPC-derived neurospheres, prior to their transplantation, with a Tet-Off Runx1-overexpressing plasmid to maintain Runx1 expression in vivo after transplantation. Although pronounced cell differentiation was found in the Runx1-expressing transplants from both cell sources, we observed extensive, long-distance growth of axons exclusively from hscNSPC-derived transplants. These axons ultimately reached the dorsal root transitional zone, the boundary separating peripheral and central nervous systems. Our data show that hscNSPCs have the potential to differentiate to projection neurons with long-distance axonal outgrowth and that Runx1 overexpression is a useful approach to induce such outgrowth in specific sources of NSPCs.

sted, utgiver, år, opplag, sider
2011. Vol. 20, nr 11, s. 1847-1857
HSV kategori
Forskningsprogram
Neurovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-161344DOI: 10.1089/scd.2010.0555ISI: 000296587400003PubMedID: 21322790OAI: oai:DiVA.org:uu-161344DiVA, id: diva2:455879
Merknad

De 2 första författarna delar förstaförfattarskapet.

Tilgjengelig fra: 2011-11-11 Laget: 2011-11-11 Sist oppdatert: 2017-12-08
Inngår i avhandling
1. Reconnecting the CNS and PNS with Stem Cell Transplantation
Åpne denne publikasjonen i ny fane eller vindu >>Reconnecting the CNS and PNS with Stem Cell Transplantation
2015 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2015. s. 54
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1105
Emneord
stem cell transplantation, regenerative neurobiology, nerve injury repair
HSV kategori
Forskningsprogram
Medicinsk vetenskap
Identifikatorer
urn:nbn:se:uu:diva-251546 (URN)978-91-554-9252-6 (ISBN)
Disputas
2015-06-08, B/C2:301, BMC, Husargatan 3, Uppsala, 10:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2015-05-18 Laget: 2015-04-20 Sist oppdatert: 2018-01-11

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekstPubMed

Person

König, NiclasVasylovska, SvitlanaNgamjariyawat, AnongnadTrolle, CarlAldskogius, HåkanKozlova, Elena N

Søk i DiVA

Av forfatter/redaktør
König, NiclasVasylovska, SvitlanaNgamjariyawat, AnongnadTrolle, CarlAldskogius, HåkanKozlova, Elena N
Av organisasjonen
I samme tidsskrift
Stem Cells and Development

Søk utenfor DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 888 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf