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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats

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Rodriguez-Sanchez, Diego Noe [1] ; Araujo Pinto, Giovana Boff [1] ; Cartarozzi, Luciana Politti [2] ; Rodrigues de Oliveira, Alexandre Leite [2] ; Carvalho Bovolato, Ana Livia [3] ; de Carvalho, Marcio [1] ; Lopes da Silva, Jorge Vicente [4] ; Dernowsek, Janaina de Andrea [4] ; Golim, Marjorie [5] ; Barraviera, Benedito [6] ; Ferreira, Rui Seabra [6] ; Deffune, Elenice [3] ; Bertanha, Mathues [3] ; Amorim, Rogerio Martins [1]
Total Authors: 14
[1] Sao Paulo State Univ, UNESP, Sch Vet Med & Anim Sci, Dept Vet Clin, Botucatu, SP - Brazil
[2] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil
[3] Sao Paulo State Univ, Blood Transfus Ctr, Botucatu Med Sch, Cell Engn Lab, Botucatu, SP - Brazil
[4] Three Dimens Technol Res Grp, Renato Archer Informat Technol Ctr CTI, Campinas, SP - Brazil
[5] Sao Paulo State Univ, Hemoctr Div, Botucatu Med Sch, Botucatu, SP - Brazil
[6] Sao Paulo State Univ, Ctr Study Venoms & Venomous Anim CEVAP, UNESP, Botucatu, SP - Brazil
Total Affiliations: 6
Document type: Journal article
Source: STEM CELL RESEARCH & THERAPY; v. 12, n. 1 MAY 29 2021.
Web of Science Citations: 1

BackgroundNerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration.Methods3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL+MSCs (NGC multi-functionalized with 10(6) canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12weeks. Morphometric analysis was performed after 8 and 12weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75(NTR) neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve.ResultsThe inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75(NTR) was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL+MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30days following repair.Conclusions3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats. (AU)

Grantee:Diego Noé Rodríguez Sánchez
Support type: Scholarships in Brazil - Doctorate