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Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects

i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-465 Porto, Portugal
INEB—Instituto de Engenharia Biomédica, University of Porto, 4200-465 Porto, Portugal
ICBAS—Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4200-465 Porto, Portugal
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(14), 3430;
Received: 16 June 2019 / Revised: 8 July 2019 / Accepted: 9 July 2019 / Published: 12 July 2019
(This article belongs to the Special Issue Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration)
PDF [312 KB, uploaded 12 July 2019]


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. View Full-Text
Keywords: regeneration; osteogenic differentiation; immunomodulation; bone repair regeneration; osteogenic differentiation; immunomodulation; bone repair

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Freitas, J.; Santos, S.G.; Gonçalves, R.M.; Teixeira, J.H.; Barbosa, M.A.; Almeida, M.I. Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects. Int. J. Mol. Sci. 2019, 20, 3430.

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