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Adipose-derived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro.
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2007 (English)In: Exp Neurol, ISSN 0014-4886, Vol. 207, no 2, 267-74 p.Article in journal (Refereed) Published
Abstract [en]

Experimentally, peripheral nerve repair can be enhanced by Schwann cell transplantation but the clinical application is limited by donor site morbidity and the inability to generate a sufficient number of cells quickly. We have investigated whether adult stem cells, isolated from adipose tissue, can be differentiated into functional Schwann cells. Rat visceral fat was enzymatically digested to yield rapidly proliferating fibroblast-like cells, a proportion of which expressed the mesenchymal stem cell marker, stro-1, and nestin, a neural progenitor protein. Cells treated with a mixture of glial growth factors (GGF-2, bFGF, PDGF and forskolin) adopted a spindle-like morphology similar to Schwann cells. Immunocytochemical staining and western blotting indicated that the treated cells expressed the glial markers, GFAP, S100 and p75, indicative of differentiation. When co-cultured with NG108-15 motor neuron-like cells, the differentiated stem cells enhanced the number of NG108-15 cells expressing neurites, the number of neurites per cell and the mean length of the longest neurite extended. Schwann cells evoked a similar response whilst undifferentiated stem cells had no effect. These results indicate adipose tissue contains a pool of regenerative stem cells which can be differentiated to a Schwann cell phenotype and may be of benefit for treatment of peripheral nerve injuries.

Place, publisher, year, edition, pages
2007. Vol. 207, no 2, 267-74 p.
Keyword [en]
Adipose Tissue/*cytology, Adult Stem Cells/drug effects/*physiology, Animals, Cell Count, Cell Differentiation/drug effects/*physiology, Cell Proliferation, Coculture Techniques/methods, Glial Fibrillary Acidic Protein/metabolism, Myelin Proteins/metabolism, Nerve Tissue Proteins/metabolism, Neuregulin-1/pharmacology, Neurites/drug effects/*physiology, Neuroblastoma/pathology, Neurons/*cytology, Rats, Rats; Sprague-Dawley, Schwann Cells/*physiology, Time Factors
URN: urn:nbn:se:umu:diva-8120DOI: 10.1016/j.expneurol.2007.06.029PubMedID: 17761164OAI: diva2:147791
Available from: 2008-01-21 Created: 2008-01-21 Last updated: 2016-02-22Bibliographically approved
In thesis
1. Nerve gap repair by the use of artificial conduits and cultured cells
Open this publication in new window or tab >>Nerve gap repair by the use of artificial conduits and cultured cells
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Peripheral nerve injuries are often associated with loss of nerve tissue and require autologous nerve grafts to provide a physical substrate for axonal growth. This thesis investigates the use of fibrin as both a tubular conduit to guide nerve regeneration and also as a matrix material to suspend various regenerative cell types within/on poly-3-hydroxybutyrate (PHB) nerve conduits. Adipose derived stem cells (ASC) are found in abundant quantities. In this thesis the ability of rat ASC to differentiate into Schwann cells was determined and a preliminary study of the neurotrophic potential of human ASC was also investigated.

Rat sciatic nerve axotomy was performed proximally in the thigh to create a 10-mm gap between the nerve stumps and the gap was bridged using the various conduits.  At early time points the nerve grafts were harvested and investigated for axonal and Schwann cell markers.  After 16 weeks the regenerative response from sensory and motor neurons was also evaluated following retrograde labelling with Fast Blue fluorescent tracer. Stem cells were treated with a mixture of glial growth factors and after 2 weeks in vitro the expression of Schwann cell markers was analysed by immunocytochemistry and Western blotting.  ASC were cocultured with the NG108-15 neuronal cell line to determine their ability to promote neurite outgrowth.  Human ASC were isolated from the deep and superficial layers of abdominal fat tissue obtained during abdominoplasty procedures.  RT-PCR was used to investigate the expression of neurotrophic factors.

Immunohistochemistry showed a superior nerve regeneration distance in the fibrin conduit compared with PHB. The fibrin conduit promoted regeneration of 60% of sensory neurones and 52% of motor neurones when compared with an autograft group at 16 weeks. The total number of myelinated axons in the distal nerve stump in the fibrin-conduit group reached 86% of the graft and the weight of gastrocnemius and soleus muscles recovered to 82% and 89% of the controls, respectively. In vitro studies showed that rat ASC could be differentiated to a Schwann cell phenotype. These treated cells enhanced both the number of NG108-15 cells expressing neurites and neurite length. In the same coculture model system, human superficial fat layer ASC induced significantly enhanced neurite outgrowth when compared with the deep layer fat cells. RT-PCR analysis showed ASC isolated from both layers expressed neurotrophic factors.

These results indicate that a tubular fibrin conduit can be used to promote neuronal regeneration following peripheral nerve injury. There was also a beneficial effect of using a fibrin matrix to seed cells within/on PHB conduits which should ultimately lead to improved functional recovery following nerve injury.  There might also be an advantage to use a simple strip of PHB rather than a conventional tube-like structure implying that single fascicle nerve grafting could be advantageous for nerve repair.  The results of in vitro experiments indicate adipose tissue contains a pool of regenerative stem cells which can be differentiated to a Schwann cell phenotype and given that human ASC express a range of neurotrophic factors they are likely to be of clinical benefit for treatment of peripheral nerve injuries.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2010. 54 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1369
adipose stem cells, cell matrix, fibrin, nerve conduit, nerve gap
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Research subject
urn:nbn:se:umu:diva-35582 (URN)978-91-7459-038-8 (ISBN)
Public defence
2010-09-20, BiA201, Biologihuset, Umeå, 13:00 (English)
Available from: 2010-08-30 Created: 2010-08-24 Last updated: 2010-08-30Bibliographically approved

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Kalbermatten, Daniel FWiberg, Mikael
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