Mesenchymal stem cells engrafted in a fibrin scaffold stimulate Schwann cell reactivity and axonal regeneration following sciatic nerve tubulization

Author(s)

Cartarozzi, Luciana P. ^[1] ; Spejo, Aline B. ^[1] ; Ferreira, Jr., Rui S. ^[2] ; Barraviera, Benedito ^[2] ; Duek, Eliana ^[3] ; Carvalho, Juliana L. ^[4] ; Goes, Alfredo M. ^[4] ; Oliveira, Alexandre L. R. ^[1]

Affiliation

^[1] Univ Estadual Campinas, Dept Struct & Funct Biol, BR-13083970 Campinas, SP - Brazil

^[2] UNESP, CEVAP, BR-18610307 Botucatu, SP - Brazil

^[3] Univ Estadual Campinas, Fac Mech Engn, BR-13083860 Campinas, SP - Brazil

^[4] Univ Fed Minas Gerais, Inst Biol Sci, BR-30121970 Belo Horizonte, MG - Brazil

• Document type: Journal article
• Source: Brain Research Bulletin; v. 112, p. 14-24, MAR 2015.
• Web of Science Citations: 22

Abstract

The present study investigated the effectiveness of mesenchymal stem cells (MSCs) associated with a fibrin scaffold (FS) for the peripheral regenerative process after nerve tubulization. Adult female Lewis rats received a unilateral sciatic nerve transection followed by repair with a polycaprolactone (PCL)-based tubular prosthesis. Sixty days after injury, the regenerated nerves were studied by immunohistochemistry. Anti-p75NTR immunostaining was used to investigate the reactivity of the MSCs. Basal labeling, which was upregulated during the regenerative process, was detected in uninjured nerves and was significantly greater in the MSC-treated group. The presence of GFP-positive MSCs was detected in the nerves, indicating the long term survival of such cells. Moreover, there was co-localization between MSCs and BNDF immunoreactivity, showing a possible mechanism by which MSCs improve the reactivity of SCs. Myelinated axon counting and morphometric analyses showed that MSC engrafting led to a higher degree of fiber compaction combined with a trend of increased myelin sheath thickness, when compared with other groups. The functional result of MSC engrafting was that the animals showed higher motor function recovery at the seventh and eighth week after lesion. The findings herein show that MSC+FS therapy improves the nerve regeneration process by positively modulating the reactivity of SCs. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 14/06892-3 - Use of mesenchymal stem cells in the CNS/PNS interface: repair of proximal lesions
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/08101-8 - In vivo imaging of nerve regeneration following ventral root replantation with fluo-stained fibrin sealant associated with mesenchymal stem cells
• Grantee: Rui Seabra Ferreira Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis
• Grantee: Suely Vilela
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/53846-9 - Recent acquisition of preparative high-performance liquid chromatograph for the purification and isolation of serine proteinases to produce fibrin sealant
• Grantee: Benedito Barraviera
• Support Opportunities: Multi-user Equipment Program