Resveratrol enhances the functionality and improves the regeneration of mesenchymal stem cell aggregates

• Published in: Experimental & molecular medicine 2018, 50(0), , pp.1-15
• Main Authors: Wang, Yi-Jing, Zhao, Pan, Sui, Bing-Dong, Liu, Nu, Hu, Cheng-Hu, Chen, Ji, Zheng, Chen-Xi, Liu, An-Qi, Xuan, Kun, Pan, Ya-Ping, Jin, Yan
• Format: Article
• Language: English
• Subjects: 13/1; 13/100; 13/107; 13/21; 13/31; 13/51; 13/95; 14/63; 38/77; 631/532/2074; 631/532/489; 631/61/2035; 64/60; 692/308/153; 692/308/575; 96/98; Adult; Autografts; Biomedical and Life Sciences; Biomedicine; Data processing; Female; Humans; Inflammation; Male; Medical Biochemistry; Mesenchymal Stem Cells - metabolism; Mesenchymal Stem Cells - pathology; Mesenchyme; Microenvironments; Molecular Medicine; Osteogenesis; Patients; Periodontal ligament; Periodontal Ligament - metabolism; Periodontal Ligament - pathology; Periodontitis; Periodontitis - metabolism; Periodontitis - pathology; Regeneration - drug effects; Regenerative medicine; Resveratrol; Resveratrol - pharmacokinetics; Stem Cells; Tumor necrosis factor-TNF; Tumor necrosis factor-α; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-018-0109-y

Mesenchymal stem cell (MSC)-based regeneration, specifically cell aggregate or cell sheet engineering, is a promising approach for tissue reconstruction. Considering the advantages of ease of harvest and lack of immune rejection, the application of autologous MSCs (i.e., patients’ own MSCs) in regenerative medicine has developed considerable interest. However, the impaired cell viability and regenerative potential following MSCs impacted by disease remain a major challenge. Resveratrol (RSV) exhibits reliable and extensive rejuvenative activities that have received increasing clinical attention. Here, we uncovered that resveratrol enhances the functionality and improves the regeneration of mesenchymal stem cell aggregates. Periodontal ligament MSCs (PDLSCs) from normal control subjects (N-PDLSCs) and periodontitis patients (P-PDLSCs) were investigated. Compared to N-PDLSCs, P-PDLSCs were less capable of forming cell aggregates, and P-PDLSC aggregates showed impaired osteogenesis and regeneration. These functional declines could be mimicked in N-PDLSCs by tumor necrosis factor alpha (TNF-α) treatment. Notably, a TNF-α-induced functional decline in N-PDLSC aggregates was rescued by RSV application. More importantly, in both N-PDLSCs and P-PDLSCs, RSV promoted cell aggregate formation and improved their osteogenic potential. Furthermore, as proven ectopically in vivo, the tissue regenerative capability of P-PDLSC aggregates was also enhanced after RSV treatment during aggregate formation in vitro. Finally, in a rat in situ regeneration model, we successfully applied both N-PDLSC aggregates and P-PDLSC aggregates to repair periodontal defects upon long-term functional improvements by RSV preconditioning. Together, our data unravel a novel methodology for using pharmacology (i.e., RSV)-based cell aggregate engineering to improve the functionality and facilitate the regeneration of MSCs from both healthy and inflammatory microenvironments, shedding light on improving the application of autologous MSC-mediated regenerative medicine. Regenerative medicine: Red wine compound helps rejuvenate stem cells A molecule found in the skin of red grapes enhances the regenerative capacity of adult stem cells. Researchers in China led by Yan Jin from Fourth Military Medical University, Xi’an, and Ya-Ping Pan from China Medical University, Shenyang, isolated stem cells capable of making the different specialized cells found in the skeletal tissues from the connective tissue lo