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Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects
The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678255/ https://www.ncbi.nlm.nih.gov/pubmed/31336890 http://dx.doi.org/10.3390/ijms20143430 |
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author | Freitas, Jaime Santos, Susana Gomes Gonçalves, Raquel Madeira Teixeira, José Henrique Barbosa, Mário Adolfo Almeida, Maria Inês |
author_facet | Freitas, Jaime Santos, Susana Gomes Gonçalves, Raquel Madeira Teixeira, José Henrique Barbosa, Mário Adolfo Almeida, Maria Inês |
author_sort | Freitas, Jaime |
collection | PubMed |
description | The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair. |
format | Online Article Text |
id | pubmed-6678255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66782552019-08-19 Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects Freitas, Jaime Santos, Susana Gomes Gonçalves, Raquel Madeira Teixeira, José Henrique Barbosa, Mário Adolfo Almeida, Maria Inês Int J Mol Sci Review The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair. MDPI 2019-07-12 /pmc/articles/PMC6678255/ /pubmed/31336890 http://dx.doi.org/10.3390/ijms20143430 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Freitas, Jaime Santos, Susana Gomes Gonçalves, Raquel Madeira Teixeira, José Henrique Barbosa, Mário Adolfo Almeida, Maria Inês Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects |
title | Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects |
title_full | Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects |
title_fullStr | Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects |
title_full_unstemmed | Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects |
title_short | Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects |
title_sort | genetically engineered-msc therapies for non-unions, delayed unions and critical-size bone defects |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678255/ https://www.ncbi.nlm.nih.gov/pubmed/31336890 http://dx.doi.org/10.3390/ijms20143430 |
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