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Boundary cap neural crest stem cell transplants contribute Mts1/S100A4-expressing cells in the glial scar
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Regenerativ neurobiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Regenerativ neurobiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Regenerativ neurobiologi.ORCID-id: 0000-0001-5602-0850
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Regenerativ neurobiologi.
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2017 (Engelska)Ingår i: Regenerative Medicine, ISSN 1746-0751, E-ISSN 1746-076X, Vol. 12, nr 4, s. 339-351Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

AIM: During development, boundary cap neural crest stem cells (bNCSCs) assist sensory axon growth into the spinal cord. Here we repositioned them to test if they assist regeneration of sensory axons in adult mice after dorsal root avulsion injury.

MATERIALS & METHODS: Avulsed mice received bNCSC or human neural progenitor (hNP) cell transplants and their contributions to glial scar formation and sensory axon regeneration were analyzed with immunohistochemistry and transganglionic tracing.

RESULTS: hNPs and bNCSCs form similar gaps in the glial scar, but unlike hNPs, bNCSCs contribute Mts1/S100A4 (calcium-binding protein) expression to the scar and do not assist sensory axon regeneration.

CONCLUSION: bNCSC transplants contribute nonpermissive Mts1/S100A4-expressing cells to the glial scar after dorsal root avulsion.

Ort, förlag, år, upplaga, sidor
2017. Vol. 12, nr 4, s. 339-351
Nyckelord [en]
calcium-binding protein, glia, nerve degeneration, neural stem cell, sensory neuron, spinal cord
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:uu:diva-328589DOI: 10.2217/rme-2016-0163ISI: 000406147100006PubMedID: 28621171OAI: oai:DiVA.org:uu-328589DiVA, id: diva2:1136354
Forskningsfinansiär
Vetenskapsrådet, 20716Tillgänglig från: 2017-08-28 Skapad: 2017-08-28 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
Ingår i avhandling
1. Neural progenitors for sensory and motor repair
Öppna denna publikation i ny flik eller fönster >>Neural progenitors for sensory and motor repair
2017 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Injury and neurodegenerative conditions of the spinal cord can lead to paralysis and loss of sensation. Cell therapeutic approaches can restore sensory innervation of the spinal cord following injury and protect spinal cord cells from degeneration. This thesis primarily focuses on the restoration of deaffarented sensory fibres following injury to the dorsal root and spinal cord. These injuries lead to the formation of a non-permissive glial scar that prevents sensory axons from reinnervating spinal cord targets. It takes advantage of a dorsal root injury model that closely mimics spinal root avulsion injuries occurring in humans. In the first part of the thesis, three different neural progenitor types from human or murine sources are tested for their regenerative properties following their transplantation to the site of dorsal root avulsion injury. In the second part, the ability of murine neural progenitors to protect spinal motor neurons from a neurodegenerative process is tested.

In the first original research article, I show that human embryonic stem cell derived neural progenitors are able to restore sensorimotor functions, mediated by the formation of a tissue bridge that allows ingrowth of sensory axons into the spinal cord. In the second research article, I present that murine boundary cap neural crest stem cells, a special type of neural progenitor that governs the entry of sensory axons into the spinal cord during development, are unable to form a permissive tissue bridge. This is possibly caused by the contribution of transplant derived ingrowth non-permissive glial cells. In the third research article, I show that human neural progenitors derived from foetal sources are capable of stimulating sensory ingrowth and that they ameliorate the glial scar. When this approach is combined with the delivery of sensory outgrowth stimulating neurotrophic factors, these cells fail to form a permissive tissue bridge and fail to modify the glial scar. In the final research article, murine boundary cap neural crest stem cells are shown to protect motor neurons, which harbor an amyotrophic lateral sclerosis causing mutation, from oxidative stress. Oxidative stress is a pathological component of amyotrophic lateral sclerosis in human patients.

Taken together, this thesis provides first evidence that sensory regeneration following a spinal root avulsion injury can be achieved by transplantation of human neural progenitors. In addition, it introduces murine boundary cap neural crest stem cells as interesting candidates for the cell therapeutic treatment of amyotrophic lateral sclerosis.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2017. s. 67
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1365
Nyckelord
Regenerative Neurobiology, Stem cells, Sensory regeneration, Spinal cord injury, Amyotrophic Lateral Sclerosis, Neurodegeneration, Oxidative Stress
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
Medicinsk vetenskap
Identifikatorer
urn:nbn:se:uu:diva-328590 (URN)978-91-513-0058-0 (ISBN)
Disputation
2017-10-23, B/C8:305, Husargatan 3, Uppsala, 10:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2017-10-02 Skapad: 2017-08-31 Senast uppdaterad: 2018-01-13

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