PMID- 28629798 OWN - NLM STAT- MEDLINE DCOM- 20180525 LR - 20181202 IS - 1876-7737 (Electronic) IS - 1874-3919 (Linking) VI - 165 DP - 2017 Aug 8 TI - Proteomic analysis of mesenchymal to Schwann cell transdifferentiation. PG - 93-101 LID - S1874-3919(17)30221-X [pii] LID - 10.1016/j.jprot.2017.06.011 [doi] AB - While transplantation of Schwann cells facilitates axon regeneration, remyelination and repair after peripheral nerve injury clinical use is limited by cell bioavailability. We posit that such limitation in cell access can be overcome by the use of autologous bone-marrow derived mesenchymal stem cells (MSCs). As MSCs can transdifferentiate to Schwann cell-phenotypes and accelerate nerve regeneration we undertook proteomic evaluation of the cells to uncover the protein contents that affects Schwann cell formulation. Transdifferentiated MSCs secrete significant amounts of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in cell-conditioned media that facilitated neurite outgrowth. MSC proteins significantly regulated during Schwann cell transdifferentiation included, but were not limited to, GNAI2, MYL9, ACTN4, ACTN1, ACTB, CAV-1, HSPB1, PHB2, TBB4B, CTGF, TGFI1, ARF6, EZR, GELS, VIM, WNT5A, RTN4, EFNB1. These support axonal guidance, myelination, neural development and neural growth and differentiation. The results unravel the molecular events that underlie cell transdifferentiation that ultimately serve to facilitate nerve regeneration and repair in support of cell transplantation. SIGNIFICANCE STATEMENT: While Schwann cells facilitate axon regeneration, remyelination and repair after peripheral nerve injury clinical use is limited by cell bioavailability. We posit that such limitation in cell access can be overcome by the use of bone-marrow derived mesenchymal stem cells (MSCs) transdifferentiated to Schwann cell-phenotypes. In the present study, we undertook the first proteomic evaluation of these transdifferentiated cells to uncover the protein contents that affects Schwann cell formulation. Furthermore, these transdifferentiated MSCs secrete significant amounts of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in cell-conditioned media that facilitated neurite outgrowth. Our results demonstrate that a number of MSC proteins were significantly regulated following transdifferentiation of the MSCs supporting roles in axonal guidance, myelination, neural development and differentiation. The conclusions of the present work unravel the molecular events that underlie cell transdifferentiation that ultimately serve to facilitate nerve regeneration and repair in support of cell transplantation. Our study was the first proteomic comparison demonstrating the transdifferentiation of MSCs and these reported results can affect a wide field of stem cell biology, tissue engineering, and proteomics. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Sharma, Anup D AU - Sharma AD AD - Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011-2230, USA; Neuroscience Program, Iowa State University, Ames, IA 50011, USA. FAU - Wiederin, Jayme AU - Wiederin J AD - Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA. FAU - Uz, Metin AU - Uz M AD - Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011-2230, USA. FAU - Ciborowski, Pawel AU - Ciborowski P AD - Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA. FAU - Mallapragada, Surya K AU - Mallapragada SK AD - Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011-2230, USA; Neuroscience Program, Iowa State University, Ames, IA 50011, USA. FAU - Gendelman, Howard E AU - Gendelman HE AD - Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA. FAU - Sakaguchi, Donald S AU - Sakaguchi DS AD - Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011-1031, USA; Neuroscience Program, Iowa State University, Ames, IA 50011, USA. Electronic address: dssakagu@iastate.edu. LA - eng GR - P30 GM103509/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20170617 PL - Netherlands TA - J Proteomics JT - Journal of proteomics JID - 101475056 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 9061-61-4 (Nerve Growth Factor) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/analysis MH - *Cell Transdifferentiation MH - Cells, Cultured MH - Mesenchymal Stem Cells/chemistry/*cytology MH - Nerve Growth Factor/analysis MH - Nerve Regeneration MH - Proteomics/*methods MH - Rats MH - Schwann Cells/chemistry/*cytology OTO - NOTNLM OT - Axon regeneration OT - Brain-derived neurotrophic factor OT - Mesenchymal stem cells OT - Nerve growth factor OT - Neurite outgrowth OT - Peripheral nerve regeneration OT - Proteomics OT - Remyelination OT - Schwann cells OT - Systems biology OT - Transdifferentiation EDAT- 2017/06/21 06:00 MHDA- 2018/05/26 06:00 CRDT- 2017/06/21 06:00 PHST- 2017/04/18 00:00 [received] PHST- 2017/05/31 00:00 [revised] PHST- 2017/06/13 00:00 [accepted] PHST- 2017/06/21 06:00 [pubmed] PHST- 2018/05/26 06:00 [medline] PHST- 2017/06/21 06:00 [entrez] AID - S1874-3919(17)30221-X [pii] AID - 10.1016/j.jprot.2017.06.011 [doi] PST - ppublish SO - J Proteomics. 2017 Aug 8;165:93-101. doi: 10.1016/j.jprot.2017.06.011. Epub 2017 Jun 17.