Genetically engineered-MSC therapies for non-unions, delayed unions and critical-size bone defects

Autor: José H. Teixeira, Susana G. Santos, Jaime Freitas, Maria Inês Almeida, Raquel Gonçalves, Mário A. Barbosa
Přispěvatelé: Instituto de Investigação e Inovação em Saúde
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Bone Regeneration
Review
immunomodulation
lcsh:Chemistry
Fractures
Bone
Mesenchymal Stem Cell Transplantation / methods
Osteogenesis
Osteogenic differentiation
lcsh:QH301-705.5
Spectroscopy
Fracture Healing
Clinical Studies as Topic
Cell Differentiation
General Medicine
Mesenchymal Stem Cells / metabolism
Computer Science Applications
Treatment Outcome
Bone repair
Fractures
Bone / pathology
Genetic Engineering
Genetic Engineering / methods
Cell type
Stromal cell
Fractures
Bone / etiology
osteogenic differentiation
Context (language use)
Bone healing
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells / cytology
Catalysis
Inorganic Chemistry
Immunomodulation
Fractures
Bone / therapy
medicine
Regeneration
Animals
Humans
Physical and Theoretical Chemistry
Bone regeneration
Molecular Biology
business.industry
Regeneration (biology)
Organic Chemistry
Mesenchymal stem cell
Mesenchymal Stem Cells
Bone fracture
medicine.disease
bone repair
Disease Models
Animal
lcsh:Biology (General)
lcsh:QD1-999
regeneration
Cancer research
business
Biomarkers
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 14, p 3430 (2019)
International Journal of Molecular Sciences
Popis: 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. This project is supported by Fundação para a Ciência e a Tecnologia (FCT)—in the framework of the project POCI-01-0145-FEDER-031402-R2Bone, under the PORTUGAL 2020 Partnership Agreement, through ERDF, co-funded by FEDER/FNR, and national funding (through FCT – Fundação para a Ciência e a Tecnologia, I.P., provided by the contract-program and according to numbers 4, 5 and 6 of art. 23 of Law No. 57/2016 of 29 August 2016, as amended by Law No. 57/2017 of 19 July 2017). RG, JHT, and MIA are supported by FCT, through the FCT Investigator Program (IF/00638/2014), SFRH/BD/112832/2015, and DL 57/2016/CP1360/CT0008, respectively.
Databáze: OpenAIRE
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