Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs)

Dorsal root rhizotomy (DRZ) is currently considered an untreatable injury, resulting in the loss of sensitive function and usually leading to neuropathic pain. In this context, we recently proposed a new surgical approach to treat DRZ that uses platelet-rich plasma (PRP) gel to restore the spinal re...

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Main Authors: Mateus Vidigal de Castro, Moníze Valéria Ramos da Silva, Gabriela Bortolança Chiarotto, Maria Helena Andrade Santana, Ângela Cristina Malheiros Luzo, Sergiy Kyrylenko, Alexandre Leite Rodrigues de Oliveira
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2020/8834360
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author Mateus Vidigal de Castro
Moníze Valéria Ramos da Silva
Gabriela Bortolança Chiarotto
Maria Helena Andrade Santana
Ângela Cristina Malheiros Luzo
Sergiy Kyrylenko
Alexandre Leite Rodrigues de Oliveira
author_facet Mateus Vidigal de Castro
Moníze Valéria Ramos da Silva
Gabriela Bortolança Chiarotto
Maria Helena Andrade Santana
Ângela Cristina Malheiros Luzo
Sergiy Kyrylenko
Alexandre Leite Rodrigues de Oliveira
author_sort Mateus Vidigal de Castro
collection DOAJ
description Dorsal root rhizotomy (DRZ) is currently considered an untreatable injury, resulting in the loss of sensitive function and usually leading to neuropathic pain. In this context, we recently proposed a new surgical approach to treat DRZ that uses platelet-rich plasma (PRP) gel to restore the spinal reflex. Success was correlated with the reentry of primary afferents into the spinal cord. Here, aiming to enhance previous results, cell therapy with bioengineered human embryonic stem cells (hESCs) to overexpress fibroblast growth factor 2 (FGF2) was combined with PRP. For these experiments, adult female rats were submitted to a unilateral rhizotomy of the lumbar spinal dorsal roots, which was followed by root repair with PRP gel with or without bioengineered hESCs. One week after DRZ, the spinal cords were processed to evaluate changes in the glial response (GFAP and Iba-1) and excitatory synaptic circuits (VGLUT1) by immunofluorescence. Eight weeks postsurgery, the lumbar intumescences were processed for analysis of the repaired microenvironment by transmission electron microscopy. Spinal reflex recovery was evaluated by the electronic Von Frey method for eight weeks. The transcript levels for human FGF2 were over 37-fold higher in the induced hESCs than in the noninduced and the wildtype counterparts. Altogether, the results indicate that the combination of hESCs with PRP gel promoted substantial and prominent axonal regeneration processes after DRZ. Thus, the repair of dorsal roots, if done appropriately, may be considered an approach to regain sensory-motor function after dorsal root axotomy.
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spelling doaj-art-c9f66832c04441ba87bdfca38079c7172025-02-03T06:05:34ZengWileyStem Cells International1687-966X1687-96782020-01-01202010.1155/2020/88343608834360Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs)Mateus Vidigal de Castro0Moníze Valéria Ramos da Silva1Gabriela Bortolança Chiarotto2Maria Helena Andrade Santana3Ângela Cristina Malheiros Luzo4Sergiy Kyrylenko5Alexandre Leite Rodrigues de Oliveira6Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, BrazilDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, BrazilDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, BrazilDepartment of Engineering of Materials and Bioprocesses, School of Chemical Engineering, University of Campinas, Campinas, São Paulo, BrazilHaematology and Hemotherapy Center, Umbilical Cord Blood Bank, University of Campinas, Campinas, São Paulo, BrazilDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, BrazilDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, BrazilDorsal root rhizotomy (DRZ) is currently considered an untreatable injury, resulting in the loss of sensitive function and usually leading to neuropathic pain. In this context, we recently proposed a new surgical approach to treat DRZ that uses platelet-rich plasma (PRP) gel to restore the spinal reflex. Success was correlated with the reentry of primary afferents into the spinal cord. Here, aiming to enhance previous results, cell therapy with bioengineered human embryonic stem cells (hESCs) to overexpress fibroblast growth factor 2 (FGF2) was combined with PRP. For these experiments, adult female rats were submitted to a unilateral rhizotomy of the lumbar spinal dorsal roots, which was followed by root repair with PRP gel with or without bioengineered hESCs. One week after DRZ, the spinal cords were processed to evaluate changes in the glial response (GFAP and Iba-1) and excitatory synaptic circuits (VGLUT1) by immunofluorescence. Eight weeks postsurgery, the lumbar intumescences were processed for analysis of the repaired microenvironment by transmission electron microscopy. Spinal reflex recovery was evaluated by the electronic Von Frey method for eight weeks. The transcript levels for human FGF2 were over 37-fold higher in the induced hESCs than in the noninduced and the wildtype counterparts. Altogether, the results indicate that the combination of hESCs with PRP gel promoted substantial and prominent axonal regeneration processes after DRZ. Thus, the repair of dorsal roots, if done appropriately, may be considered an approach to regain sensory-motor function after dorsal root axotomy.http://dx.doi.org/10.1155/2020/8834360
spellingShingle Mateus Vidigal de Castro
Moníze Valéria Ramos da Silva
Gabriela Bortolança Chiarotto
Maria Helena Andrade Santana
Ângela Cristina Malheiros Luzo
Sergiy Kyrylenko
Alexandre Leite Rodrigues de Oliveira
Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs)
Stem Cells International
title Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs)
title_full Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs)
title_fullStr Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs)
title_full_unstemmed Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs)
title_short Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs)
title_sort spinal reflex recovery after dorsal rhizotomy and repair with platelet rich plasma prp gel combined with bioengineered human embryonic stem cells hescs
url http://dx.doi.org/10.1155/2020/8834360
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