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

Abstract:

: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.

journal_name

Int J Mol Sci

authors

Freitas J,Santos SG,Gonçalves RM,Teixeira JH,Barbosa MA,Almeida MI

doi

10.3390/ijms20143430

subject

Has Abstract

pub_date

2019-07-12 00:00:00

issue

14

issn

1422-0067

pii

ijms20143430

journal_volume

20

pub_type

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