PMID- 21423756 OWN - NLM STAT- MEDLINE DCOM- 20110705 LR - 20211020 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 6 IP - 3 DP - 2011 Mar 14 TI - Adipose-derived stem cells stimulate regeneration of peripheral nerves: BDNF secreted by these cells promotes nerve healing and axon growth de novo. PG - e17899 LID - 10.1371/journal.pone.0017899 [doi] LID - e17899 AB - Transplantation of adipose-derived mesenchymal stem cells (ASCs) induces tissue regeneration by accelerating the growth of blood vessels and nerve. However, mechanisms by which they accelerate the growth of nerve fibers are only partially understood. We used transplantation of ASCs with subcutaneous matrigel implants (well-known in vivo model of angiogenesis) and model of mice limb reinnervation to check the influence of ASC on nerve growth. Here we show that ASCs stimulate the regeneration of nerves in innervated mice's limbs and induce axon growth in subcutaneous matrigel implants. To investigate the mechanism of this action we analyzed different properties of these cells and showed that they express numerous genes of neurotrophins and extracellular matrix proteins required for the nerve growth and myelination. Induction of neural differentiation of ASCs enhances production of brain-derived neurotrophic factor (BDNF) as well as ability of these cells to induce nerve fiber growth. BDNF neutralizing antibodies abrogated the stimulatory effects of ASCs on the growth of nerve sprouts. These data suggest that ASCs induce nerve repair and growth via BDNF production. This stimulatory effect can be further enhanced by culturing the cells in neural differentiation medium prior to transplantation. FAU - Lopatina, Tatiana AU - Lopatina T AD - Department of Biochemistry and Molecular Medicine, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia. t.lopatina@gmail.com FAU - Kalinina, Natalia AU - Kalinina N FAU - Karagyaur, Maxim AU - Karagyaur M FAU - Stambolsky, Dmitry AU - Stambolsky D FAU - Rubina, Kseniya AU - Rubina K FAU - Revischin, Alexander AU - Revischin A FAU - Pavlova, Galina AU - Pavlova G FAU - Parfyonova, Yelena AU - Parfyonova Y FAU - Tkachuk, Vsevolod AU - Tkachuk V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110314 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Drug Combinations) RN - 0 (GAP-43 Protein) RN - 0 (Laminin) RN - 0 (Nerve Growth Factors) RN - 0 (Proteoglycans) RN - 119978-18-6 (matrigel) RN - 9007-34-5 (Collagen) SB - IM EIN - PLoS One. 2019 Jul 12;14(7):e0219946. PMID: 31299059 MH - Adipose Tissue/*cytology MH - Animals MH - Axons/*metabolism MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Collagen/metabolism MH - Drug Combinations MH - Extracellular Matrix/metabolism MH - Female MH - GAP-43 Protein/metabolism MH - Humans MH - Implants, Experimental MH - Laminin/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Nerve Fibers/metabolism MH - Nerve Growth Factors/metabolism MH - Nerve Regeneration/*physiology MH - Peroneal Nerve/pathology/physiopathology MH - Proteoglycans/metabolism MH - Recovery of Function/physiology MH - *Stem Cell Transplantation MH - Stem Cells/cytology/*metabolism MH - *Wound Healing PMC - PMC3056777 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2011/03/23 06:00 MHDA- 2011/07/06 06:00 PMCR- 2011/03/14 CRDT- 2011/03/23 06:00 PHST- 2010/12/09 00:00 [received] PHST- 2011/02/14 00:00 [accepted] PHST- 2011/03/23 06:00 [entrez] PHST- 2011/03/23 06:00 [pubmed] PHST- 2011/07/06 06:00 [medline] PHST- 2011/03/14 00:00 [pmc-release] AID - PONE-D-10-06499 [pii] AID - 10.1371/journal.pone.0017899 [doi] PST - epublish SO - PLoS One. 2011 Mar 14;6(3):e17899. doi: 10.1371/journal.pone.0017899.