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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.
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2011 (Engelska)Ingår i: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 20, nr 11, s. 1847-1857Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
2011. Vol. 20, nr 11, s. 1847-1857
Nationell ämneskategori
Medicin och hälsovetenskap
Forskningsämne
Neurovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-161344DOI: 10.1089/scd.2010.0555ISI: 000296587400003PubMedID: 21322790OAI: oai:DiVA.org:uu-161344DiVA, id: diva2:455879
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Tillgänglig från: 2011-11-11 Skapad: 2011-11-11 Senast uppdaterad: 2017-12-08
Ingår i avhandling
1. Reconnecting the CNS and PNS with Stem Cell Transplantation
Öppna denna publikation i ny flik eller fönster >>Reconnecting the CNS and PNS with Stem Cell Transplantation
2015 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2015. s. 54
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1105
Nyckelord
stem cell transplantation, regenerative neurobiology, nerve injury repair
Nationell ämneskategori
Neurovetenskaper Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Forskningsämne
Medicinsk vetenskap
Identifikatorer
urn:nbn:se:uu:diva-251546 (URN)978-91-554-9252-6 (ISBN)
Disputation
2015-06-08, B/C2:301, BMC, Husargatan 3, Uppsala, 10:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2015-05-18 Skapad: 2015-04-20 Senast uppdaterad: 2018-01-11

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

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