Mesenchymal Stem Cells from Extra-Embryonic Tissues for Tissue Engineering – Regeneration of the Peripheral Nerve

Gärtner, Andrea; Pereira, Tiago; Gomes, Rui; Luís, Ana Lúcia; França, Miguel Lacueva; Geuna, Stefano; Armada-da-Silva, Paulo; Maurício, Ana Colette

doi:10.5772/53336

Cited by 11 publications

(34 citation statements)

References 111 publications

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“…It is important to reduce this variability in kinematics analysis to assess functional recovery after neurogenic muscle atrophy and neurotmesis/axonotmesis injuries. One evident advantage is that using a treadmill the operator reduces step-by-step variability in joint kinematics [59] which has the disadvantage of being expensive equipment. Also the possibility of combining kinematic analysis with other data, such as ground reaction forces, should be consider for a more accurate evaluation of nerve regeneration [59,64,65] .…”

Section: Discussionmentioning

confidence: 99%

“…One evident advantage is that using a treadmill the operator reduces step-by-step variability in joint kinematics [59] which has the disadvantage of being expensive equipment. Also the possibility of combining kinematic analysis with other data, such as ground reaction forces, should be consider for a more accurate evaluation of nerve regeneration [59,64,65] . Our research group has recently analyzed hip, knee and ankle joint kinematics during recovery of rat sciatic nerve axonotmesis injury, using reflective markers attached to the rat hind-limb to track the motion with infra-red capture cameras, to better assess the rat sciatic nerve model hind-limb joint kinematics during walking.…”

Section: Discussionmentioning

confidence: 99%

“…The present experimental work includes a variety of independent evaluation tools considering the morphologic and functional recovery, in order to understand and estimate the potential therapeutic benefit of a nerve repair strategy [9] . EPT, WRL, SSI and SFI, have been proven to be valid methods and to give some information to determine functional recovery following sciatic nerve injury, including motor and nociceptive evaluation [59] . The use of biomechanical techniques and rat's gait kinematic evaluation was a progress in documenting functional recovery, largely published by our research group [3,9,17,31,33,35] .…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of biodegradable electric conductive tube-guides and mesenchymal stem cells

Ribeiro¹,

Pereira²,

Caseiro³

et al. 2015

WJSC

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Evaluation of biodegradable electric conductive tube-guides and mesenchymal stem cells

Ribeiro¹,

Pereira²,

Caseiro³

et al. 2015

WJSC

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“…27,49,50 The EPT and WRL tests have been proven to be reliable, valid and highly efficient tests when it comes to determine the functional recovery following sciatic nerve injury. 93 The EPT and WRL measurements also provide a quantitative measurement of motor and sensitive function recoveries, respectively, they are simple, easy to execute, and give consistently less variation between measurements. 68 Also, SFI tests provide a quantitative measure of degree of functional deficit, but can be cumbersome, messy, time consuming, and variable, especially considering the evaluation of neurotmesis injuries recoveries, since autotomy is frequently observed in these experimental animals.…”

Section: Discussionmentioning

confidence: 99%

Regeneration of the peripheral nerve — Development and evaluation of guide tubes of biodegradable polymer

Gomes

Santos

Maurício

2017

2017 IEEE 5th Portuguese Meeting on Bioengineering (ENBENG)

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ii © Joana Gomes, 2014 iii iv ResumoDanos nas fibras nervosas periféricas resultam em perda axonal e desmielinização, seguidos de regeneração e remielinização sob condições ideais com a possibilidade de alguma recuperação funcional. Estudos recentes indicam que a diferença na regeneração axonal entre o sistema nervoso periférico (PNS) e o sistema nervoso central (CNS) resulta da presença de fatores permissivos presentes no PNS e fatores inibitórios ativos presentes no CNS.Pacientes com lesões no nervo periférico estão muitas vezes no auge da sua atividade laboral, o que faz da regeneração do nervo periférico um foco principal de pesquisa. Assim, o desafio experimental consiste em acelerar a regeneração axonal para promover a reinervação e melhorar a recuperação funcional após uma lesão no nervo periférico. Algumas das abordagens experimentais para melhorar a recuperação funcional incluem a aplicação focal de fatores neurotróficos, o bloqueio de moléculas inibidoras da regeneração axonal e o transplante de células.Depois de ocorrer uma lesão quer de axonotmese quer de neurotmese, os axónios periféricos têm a capacidade de se regenerar e de se ligar novamente aos seus alvos, sendo que no primeiro caso não há necessidade de reconstrução cirúrgica uma vez que o endoneuro, perineuro e epineuro são mantidos. No entanto, o estado funcional resultante pode não ser o melhor uma vez que a regeneração é demorada e conduz à atrofia neurogénica dos músculos regionais. Na prática clínica, a reparação cirúrgica ideal em situações de neurotmese (seccionamento total do nervo) considera-se ser a sutura topo-a-topo, de modo a aproximar o topo distal do topo proximal, sem haver tensão no local da sutura. Alternativamente, nervos autólogos são o gold standard deste tipo de procedimentos sempre que ocorre perda de substância e não seja possível executar uma sutura topo-a-topo sem tensão. No entanto, o uso de autoenxertos está limitado pelos inconvenientes inerentes uma vez que requer uma segunda cirurgia, com sacrifício de um nervo funcional, o que resulta em perda sensorial e morbidade do local de doação, entre outros.Nas últimas décadas, os diferentes tipos de enxertos artificiais ou biológicos foram desenvolvidos e investigados para que pudesse ser estabelecida uma relação entre eles e os enxertos de nervos autólogos em termos dos resultados da regeneração do nervo e da v recuperação funcional. Estes tubos-guia são projetados para preencher a lacuna existente num nervo seccionado quando existe um gap, para limitar a fibrose e orientar as fibras em regeneração na direção do topo distal. O enxerto de nervo artificial é um canal tubular feito de materiais sintéticos ou biodegradáveis e que pode orientar a regeneração do axónio sem inibir o crescimento e maturação. O canal tubular pode ser implantado vazio ou preenchido com fatores de crescimento, células ou fibras. Devido à sua capacidade de renovação, multiplicação e diferenciação, as células estaminais mesenquimatosas (MSCs) têm sido usadas para suplementar os tubos-guia, sendo ...

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“…Cell transplantation has been proposed as a method of improving peripheral nerve regeneration, enhancing axon outgrowth and survival both in vitro and in vivo [5,6]. Mesenchymal stem cells (MSCs) are one of the most interesting cell products that can be harvested from different sources, including extra-fetal tissues without any religious or ethical concern [7]. Tissue engineering of peripheral nerves associates biomaterials, some of them, previously studied by our group [1,4,8] to cellular systems, able to differentiate into neuroglial-like cells or even by modulating the inflammatory process, which might improve nerve regeneration, in terms of motor and sensory recovery, and also, by shortening the healing period avoiding regional muscular atrophy [5,6].…”

Section: Introductionmentioning

confidence: 99%

Neuro-muscular Regeneration Using Scaffolds with Mesenchymal Stem Cells (MSCs) Isolated from Human Umbilical Cord Wharton's Jelly: Functional and Morphological Analysis Using Rat Sciatic Nerve Neurotmesis Injury Model

Caseiro

Pereira

Ribeiro

et al. 2015

Procedia Engineering

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Peripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. Neonatal tissues are routinely discarded at parturition so little ethical controversy attends the harvest of the Mesenchymal Stem Cells (MSCs) which may play an important therapeutic role through the secretion of soluble trophic factors which enhance and assist in repair by paracrine activation of surrounding cells. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in our recent research work we have been evaluating the therapeutic value of MSCs isolated from the Wharton jelly (WJ) in nerve repair associated to different tube-guides made of biodegradable and biocompatible biomaterials. The WJ MSCs in vitro studies included cell characterization by immunocytochemistry, karyotype analysis, tri-lineage differentiation capacity and flow cytometry and also citocompatibility by measuring the intracellular calcium concentration ([Ca 2+ ]i) in the presence of different tube-guides.Biomaterials like PVA, PVA loaded with MWCNTs (functionalized carbon nanotubes, PVA-CNTs), PVA loaded with polypyrrole (PVA-PPy), and PLC associated to MSCs were tested in terms of cytocompatibility and in vivo in the rat sciatic nerve neurotmesis injury model. The regenerated nerves and tibialis anterior (TA) muscles were processed for stereological studies after 20 weeks. The functional recovery was assessed serially for gait biomechanical analysis, by EPT, SFI and SSI, and by WRL. Histopathology of lung, liver, kidneys, regional lymph nodes ensured the biomaterials biocompatibility. The karyotype analysis of the MSCs excluded the presence of neoplastic signs, thus supporting the suitability of isolation and expansion protocols. The MSCs were positive for C-kit, Nanog and vimentin, and negative for CD31, following the International Society for Cellular Therapy (ISCT) definition. Results obtained from epifluorescence by measuring the [Ca 2+ ]i of the MSCs cultured on tube-guides confirmed the ability to support their expansion, adhesion, and differentiation. Our results showed that the use of MSCs enhanced the recovery of sensory and motor function in neurotmesis injuries showing a thicker myelin sheath. MSCs isolated from WJ delivered through biomaterials should be regarded as a potentially valuable tool to improve clinical outcome especially after trauma to sensory nerves. In addition, these cells represent a non controversial source of primitive mesenchymal progenitor cells that can be harvested after birth, cryogenically stored, thawed, and expanded for therapeutic uses.

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Mesenchymal Stem Cells from Extra-Embryonic Tissues for Tissue Engineering – Regeneration of the Peripheral Nerve

Cited by 11 publications

References 111 publications

Evaluation of biodegradable electric conductive tube-guides and mesenchymal stem cells

Evaluation of biodegradable electric conductive tube-guides and mesenchymal stem cells

Regeneration of the peripheral nerve — Development and evaluation of guide tubes of biodegradable polymer

Neuro-muscular Regeneration Using Scaffolds with Mesenchymal Stem Cells (MSCs) Isolated from Human Umbilical Cord Wharton's Jelly: Functional and Morphological Analysis Using Rat Sciatic Nerve Neurotmesis Injury Model

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