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In vitro generation of motor neuron precursors from mouse embryonic stem cells using mesoporous nanoparticles
Stockholm University.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Regenerativ neurobiologi. (Regenerative Neurobiology)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Regenerativ neurobiologi. (Regenerative Neurobiology)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. (Regenerative Neurobiology)
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2014 (Engelska)Ingår i: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 9, nr 16, s. 2457-2466Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Aim: Stem cell-derived motor neurons (MNs) are utilized to develop replacement strategies for spinal cord disorders. Differentiation of embryonic stem cells into MN precursors involves factors and their repeated administration. We investigated if delivery of factors loaded into mesoporous nanoparticles could be effective for stem cell differentiation in vitro.

Materials & methods: We used a mouse embryonic stem cell line expressing green fluorescent protein under the promoter for the MN-specific gene Hb9 to visualize the level of MN differentiation. The differentiation of stem cells was evaluated by expression of MN-specific transcription factors monitored by quantitative real-time PCR reactions and immunocytochemistry.

Results: Mesoporous nanoparticles have strong affiliation to the embryoid bodies, penetrate inside the embryoid bodies and come in contact with differentiating cells.

Conclusion: Repeated administration of soluble factors into a culture medium can be avoided due to a sustained release effect using mesoporous silica.

Ort, förlag, år, upplaga, sidor
2014. Vol. 9, nr 16, s. 2457-2466
Nationell ämneskategori
Neurovetenskaper Medicinsk bioteknologi Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
URN: urn:nbn:se:uu:diva-224650DOI: 10.2217/nnm.14.23ISI: 000346177600004OAI: oai:DiVA.org:uu-224650DiVA, id: diva2:717653
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Tillgänglig från: 2014-05-16 Skapad: 2014-05-16 Senast uppdaterad: 2018-01-11Bibliografiskt granskad
Ingår i avhandling
1. Stem cell transplantation and regeneration after dorsal root avulsion
Öppna denna publikation i ny flik eller fönster >>Stem cell transplantation and regeneration after dorsal root avulsion
2016 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2016. s. 62
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1162
Nyckelord
Regeneration, dorsal root, sensory nerve, nerve injury, cell transplantation
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
Medicinsk vetenskap
Identifikatorer
urn:nbn:se:uu:diva-265853 (URN)978-91-554-9410-0 (ISBN)
Disputation
2016-01-08, B/C2:301, BMC, Husargatan 3, Uppsala, 10:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2015-12-17 Skapad: 2015-11-03 Senast uppdaterad: 2018-01-10

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Regenerativ neurobiologiInstitutionen för neurovetenskap
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Nanomedicine
NeurovetenskaperMedicinsk bioteknologiMedicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

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