PMID- 22020320 OWN - NLM STAT- MEDLINE DCOM- 20120406 LR - 20111214 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 199 DP - 2011 Dec 29 TI - Nerve repair with adipose-derived stem cells protects dorsal root ganglia neurons from apoptosis. PG - 515-22 LID - 10.1016/j.neuroscience.2011.09.064 [doi] AB - Novel approaches are required in the clinical management of peripheral nerve injuries because current surgical techniques result in deficient sensory recovery. Microsurgery alone fails to address extensive cell death in the dorsal root ganglia (DRG), in addition to poor axonal regeneration. Incorporation of cultured cells into nerve conduits may offer a novel approach in which to combine nerve repair and enhance axonal regeneration with neuroprotective therapies. We examined apoptotic mediator expression in rat DRG neurons following repair of a 10-mm sciatic nerve gap using a novel synthetic conduit made of poly epsilon-caprolactone (PCL) and primed with adipose-derived stem cells (ADSC) differentiated towards a Schwann cell phenotype or with primary adult Schwann cells. Differentiated ADSC expressed a range of neurotrophic factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), and neurotrophin-4 (NT4). Incorporation of either differentiated ADSC or Schwann cells significantly increased anti-apoptotic Bcl-2 mRNA expression (P<0.001) in the DRG, while significantly decreasing pro-apoptotic Bax (P<0.001) and caspase-3 mRNA (P<0.01) expression. Cleaved caspase-3 protein was observed in the DRG following nerve injury which was attenuated when nerve repair was performed using conduits seeded with cells. Cell incorporation into conduit repair of peripheral nerves demonstrates experimental promise as a novel intervention to prevent DRG neuronal loss. CI - Copyright (c) 2011 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Reid, A J AU - Reid AJ AD - Blond McIndoe Research Labs, Regenerative Biomedicine Group, University of Manchester, UK. adam.reid@manchester.ac.uk FAU - Sun, M AU - Sun M FAU - Wiberg, M AU - Wiberg M FAU - Downes, S AU - Downes S FAU - Terenghi, G AU - Terenghi G FAU - Kingham, P J AU - Kingham PJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111006 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Nerve Growth Factors) RN - 0 (Polyesters) RN - 24980-41-4 (polycaprolactone) SB - IM MH - Adipose Tissue/cytology/*transplantation MH - Animals MH - Apoptosis/physiology MH - Cell Differentiation/physiology MH - Ganglia, Spinal/*metabolism/pathology MH - Nerve Growth Factors/metabolism MH - Nerve Regeneration/*physiology MH - Neurons/cytology MH - Peripheral Nerve Injuries/surgery MH - Polyesters MH - Prostheses and Implants MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction MH - Schwann Cells/cytology/*transplantation MH - Sciatic Nerve/injuries/surgery MH - Stem Cell Transplantation/*methods MH - Tissue Engineering/*methods EDAT- 2011/10/25 06:00 MHDA- 2012/04/07 06:00 CRDT- 2011/10/25 06:00 PHST- 2011/08/02 00:00 [received] PHST- 2011/09/25 00:00 [revised] PHST- 2011/09/28 00:00 [accepted] PHST- 2011/10/25 06:00 [entrez] PHST- 2011/10/25 06:00 [pubmed] PHST- 2012/04/07 06:00 [medline] AID - S0306-4522(11)01150-X [pii] AID - 10.1016/j.neuroscience.2011.09.064 [doi] PST - ppublish SO - Neuroscience. 2011 Dec 29;199:515-22. doi: 10.1016/j.neuroscience.2011.09.064. Epub 2011 Oct 6.