title: Promoting nerve regeneration in a neurotmesis rat model using poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly: in vitro and in vivo analysis.
abstract: In peripheral nerves MSCs can modulate Wallerian degeneration and the overall regenerative response by acting through paracrine mechanisms directly on regenerating axons or upon the nerve-supporting Schwann cells. In the present study, the effect of human MSCs from Wharton's jelly (HMSCs), differentiated into neuroglial-like cells associated to poly (DL-lactide-ε-caprolactone) membrane, on nerve regeneration, was evaluated in the neurotmesis injury rat sciatic nerve model. Results in vitro showed successful differentiation of HMSCs into neuroglial-like cells, characterized by expression of specific neuroglial markers confirmed by immunocytochemistry and by RT-PCR and qPCR targeting specific genes expressed. In vivo testing evaluated during the healing period of 20 weeks, showed no evident positive effect of HMSCs or neuroglial-like cell enrichment at the sciatic nerve repair site on most of the functional and nerve morphometric predictors of nerve regeneration although the nociception function was almost normal. EPT on the other hand, recovered significantly better after HMSCs enriched membrane employment, to values of residual functional impairment compared to other treated groups. When the neurotmesis injury can be surgically reconstructed with an end-to-end suture or by grafting, the addition of a PLC membrane associated with HMSCs seems to bring significant advantage, especially concerning the motor function recovery.
authors.affiliation: Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências e Tecnologias Agrárias e Agro-Alimentares (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
authors.forename: T
authors.initials: T
authors.lastname: Pereira
authors.affiliation: Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências e Tecnologias Agrárias e Agro-Alimentares (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Gärtner
authors.affiliation: Departamento de Patologia e de Imunologia Molecular, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Instituto Português de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Amorim
authors.affiliation: Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências e Tecnologias Agrárias e Agro-Alimentares (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal ; Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), Rua Alexandre Herculano No. 321, 4000-055 Porto, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Almeida
authors.affiliation: Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências e Tecnologias Agrárias e Agro-Alimentares (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal ; Centro para o Desenvolvimento Rápido e Sustentado de Produto (CDRsp), Instituto Politécnico de Leiria (IPL), Centro Empresarial da Marinha Grande, Rua de Portugal-Zona Industrial, 2430-028 Marinha Grande, Portugal.
authors.forename: A R
authors.initials: AR
authors.lastname: Caseiro
authors.affiliation: Faculdade de Motricidade Humana (FMH), Universidade Técnica de Lisboa (UTL), Estrada da Costa, 1499-002 Cruz Quebrada-Dafundo, Portugal ; CIPER-FMH, Centro Interdisciplinar de Estudo de Performance Humana, Faculdade de Motricidade Humana (FMH), Universidade Técnica de Lisboa (UTL), Estrada da Costa, 1499-002 Cruz Quebrada-Dafundo, Portugal.
authors.forename: Paulo A S
authors.initials: PA
authors.lastname: Armada-da-Silva
authors.affiliation: CIPER-FMH, Centro Interdisciplinar de Estudo de Performance Humana, Faculdade de Motricidade Humana (FMH), Universidade Técnica de Lisboa (UTL), Estrada da Costa, 1499-002 Cruz Quebrada-Dafundo, Portugal ; UIS-IPL, Unidade de Investigação em Saúde da Escola Superior de Saúde de Leiria, Instituto Politécnico de Leiria, Morro do Lena, Alto do Vieiro, Apartado 4137, 2411-901 Leiria, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Amado
authors.affiliation: Neuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Regione Gonzole 10, Orbassano, 10043 Turin, Italy ; Department of Clinical and Biological Sciences, University of Turin, 10126 Turin, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Fregnan
authors.affiliation: Department of Veterinary Sciences, CIDESD, University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal.
authors.forename: A S P
authors.initials: AS
authors.lastname: Varejão
authors.affiliation: CEMUC, Departamento de Engenharia Metalúrgica e Materiais, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
authors.forename: J D
authors.initials: JD
authors.lastname: Santos
authors.affiliation: Centro para o Desenvolvimento Rápido e Sustentado de Produto (CDRsp), Instituto Politécnico de Leiria (IPL), Centro Empresarial da Marinha Grande, Rua de Portugal-Zona Industrial, 2430-028 Marinha Grande, Portugal ; School of Mechanical, Aerospace and Civil Engineering & Manchester Institute of Biotechnology, The University of Manchester, Manchester M13 9PL, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Bartolo
authors.affiliation: Neuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Regione Gonzole 10, Orbassano, 10043 Turin, Italy ; Department of Clinical and Biological Sciences, University of Turin, 10126 Turin, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Geuna
authors.affiliation: Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências e Tecnologias Agrárias e Agro-Alimentares (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
authors.forename: A L
authors.initials: AL
authors.lastname: Luís
authors.affiliation: Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal ; Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências e Tecnologias Agrárias e Agro-Alimentares (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal.
authors.forename: A C
authors.initials: AC
authors.lastname: Mauricio
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D008567:Membranes, Artificial; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D011091:Polyesters / Q000494:pharmacology*; D051381:Rats; D011930:Reaction Time; D012018:Reflex / Q000187:drug effects; D015203:Reproducibility of Results; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D059631:Wharton Jelly / Q000166:cytology*
chemical_list: D008567:Membranes, Artificial; D011091:Polyesters; C062968:lactide-caprolactone copolymer