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Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects
Jaime Freitas1,2, Susana Gomes Santos1,2,3, Raquel Madeira Gonçalves1,2
1i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-465 Porto, Portugal.
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.
Insights
Mesenchymal stem/stromal cells (MSCs) show promise for bone regeneration. Genetic engineering can enhance MSCs to improve bone healing in critical-size defects, offering new therapeutic strategies.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Orthopedic Research
Background:
- Bone regeneration is complex, often failing in large defects, leading to non-unions.
- Current therapies for bone defects are insufficient, necessitating novel approaches.
- Mesenchymal stem/stromal cells (MSCs) show potential for promoting bone repair.
Purpose of the Study:
- To review molecular candidates for enhancing MSCs for bone regeneration.
- To discuss methodologies for engineering and delivering MSCs.
- To evaluate the potential of MSCs and genetically engineered MSCs in bone fracture repair.
Main Methods:
- Literature review of in vivo animal studies on MSCs for bone regeneration.
- Analysis of genetic engineering strategies to improve MSC function (proliferation, osteogenesis, immunomodulation).
- Review of studies on MSC secretome and clinical trials involving MSCs.
Main Results:
- Specific molecular targets can enhance MSC pro-regenerative properties.
- Genetic engineering and optimized delivery methods show promise in preclinical models.
- Clinical studies indicate positive outcomes for MSC-based bone regeneration.
Conclusions:
- Genetically engineered MSCs offer enhanced potential for accelerating bone healing.
- MSC secretome and clinical applications warrant further investigation.
- MSCs and their engineered counterparts represent a promising therapeutic avenue for bone regeneration.
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