Human Adipose-Derived Mesenchymal Stem Cells Systemically Injected Promote Peripheral Nerve Regeneration in the Mouse Model of Sciatic Crush
- 1 June 2012
- journal article
- research article
- Published by Mary Ann Liebert Inc in Tissue Engineering, Part A
- Vol. 18 (11-12), 1264-1272
- https://doi.org/10.1089/ten.tea.2011.0491
Abstract
Mesenchymal stem cells (MSCs) represent a promising therapeutic approach in nerve tissue engineering. To date, the local implantation of MSC in injured nerves has been the only route of administration used. In case of multiple sites of injury, the systemic administration of cells capable of reaching damaged nerves would be advisable. In this regard, we found that an intravenous administration of adipose-derived MSC (ASC) 1 week after sciatic nerve crush injury, a murine model of acute axonal damage, significantly accelerated the functional recovery. Sciatic nerves from ASC-treated mice showed the presence of a restricted number of undifferentiated ASC together with a significant improvement in fiber sprouting and the reduction of inflammatory infiltrates for up to 3 weeks. Besides the immune modulatory effect, our results show that ASC may contribute to peripheral nerve regeneration because of their ability to produce in culture neuroprotective factors such as insulin-like growth factor I, brain-derived neurotrophic factor, or basic fibroblast growth factor. In addition to this production in vitro, we interestingly found that the concentration of glial-derived neurotrophic factor (GDNF) was significantly increased in the sciatic nerves in mice treated with ASC. Since no detectable levels of GDNF were observed in ASC cultures, we hypothesize that ASC induced the local production of GDNF by Schwann cells. In conclusion, we show that systemically injected ASC have a clear therapeutic potential in an acute model of axonal damage. Among the possible mechanisms promoting nerve regeneration, our results rule out a process of trans-differentiation and rather suggest the relevance of a bystander effect, including the production of in situ molecules, which, directly or indirectly through a cross-talk with local glial cells, may modulate the local environment with the down-regulation of inflammation and the promotion of axonal regeneration.Keywords
This publication has 42 references indexed in Scilit:
- Function and mechanism of axonal targeting of voltage-sensitive potassium channelsProgress in Neurobiology, 2011
- Construction of tissue engineered nerve grafts and their application in peripheral nerve regenerationProgress in Neurobiology, 2011
- Repairing injured peripheral nerves: Bridging the gapProgress in Neurobiology, 2010
- Measuring nerve regeneration in the mouseExperimental Neurology, 2010
- Transplantation of bone marrow stromal cells for peripheral nerve repairExperimental Neurology, 2007
- Peripheral nerve regeneration by transplantation of bone marrow stromal cell—derived Schwann cells in adult ratsJournal of Neurosurgery, 2004
- Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nervesExperimental Neurology, 2004
- Transplanted neuronal progenitor cells in a peripheral nerve gap promote nerve repairBrain Research, 2003
- Nerve Injury, Axonal Degeneration and Neural Regeneration: Basic InsightsBrain Pathology, 1999
- Mechanisms of Immune Regulation in the Peripheral Nervous SystemBrain Pathology, 1999