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

• Published in: Experimental & molecular medicine Vol. 50; no. 6; 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: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2018; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• 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; 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 located at the root of tooth-bearing bones. They showed that stem cells taken from people with serious gum disease could not mature and develop into tissue-forming aggregates as well as stem cells taken from healthy individuals. Treatment of healthy stem cells with a pro-inflammatory signaling molecule impaired development, but subsequent exposure to resveratrol, the compound in grape skin, restored cellular health. Resveratrol also promoted regeneration in the diseased stem cells and in rodent models of gum disease.