Human Olfactory-derived Mesenchymal Stem Cell Transplantation as a Candidate for CNS Repair

Lindsay, S. , Toft, A., Riddell, J. and Barnett, S. C. (2013) Human Olfactory-derived Mesenchymal Stem Cell Transplantation as a Candidate for CNS Repair. Glia 63(S1):E428. Meeting Abstract: XII European Meeting on Glial Cell Function in Health and Disease, Bilbao, Spain, 15-18th July 2015. (doi: 10.1002/glia.22870)

Abstract

Previously we have identified and characterised a source of adult MSCs from the uniquely regenerative human olfactory mucosa (OM-MSCs) and shown that they have enhanced clonogenicity, proliferation rate and in vitro CNS myelination compared to bone marrow derived MSCs (BM-MSCs). For comparison of the two MSC types, microRNA-based (miRNA) fingerprinting was carried out, which demonstrated 64% homology between the two MSC types. Interestingly, 26 miRNAs were differentially expressed, and of these, we focussed on miR-146a-5p due to its reported role in the regulation of chemokine production. We found that CXCL12, a chemokine regulated by this microRNA was differentially secreted by OM-MSCs. Addition of CXCL12 to myelinating cultures promoted myelination and a selective CXCL12 receptor blocker and anti-CXCL12 prevented the promyelinating effect. Transduction with the miR-140-5p antagomir and mimic produced inverse changes in CXCL12 RNA, confirming the regulatory role of miR-140-5p for CXCL12. To assess the repair potential of human OM-MSCs GFP tagged-cells were transplanted 3 weeks post-injury into the spinal cord of rats with a thoracic level 9 injury. Cells filled the lesion surviving until at least 4 weeks post-transplant and resulted in reduced level of cavitation, and a greater amount of neurofilament positive fibres within the lesion site. Data obtained using a treadmill-based gait analysis system suggested that transplanted animals recovered co-ordinated stepping earlier than control animals with immunohistochemical assessment revealing enhanced peripheral myelination within the cavity and within ventral and lateral areas of the cord by invading Schwann cells. These data suggest that OM-MSCs promote both de novo myelination and re-myelination of injured/spared axons which could account for the quicker restoration of co-ordinated stepping that was found within transplanted animals. Thus, tissue niche may play an important role in determining how beneficial a particular MSC type might be in terms of SCI repair and that OM-MSCs which promote myelination could be a better MSC choice for use in the clinic.

• Item Type: Conference or Workshop Item
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Riddell, Professor John and Barnett, Professor Susan and Lindsay, Dr Susan
• Authors: Lindsay, S., Toft, A., Riddell, J., and Barnett, S. C.
• Subjects: Q Science > Q Science (General); Q Science > QP Physiology
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• ISSN: 1098-1136