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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:50

Enthalten in:

Experimental & molecular medicine - 50(2018), 6 vom: 27. Juni, Seite 1-15

Sprache:

Englisch

Beteiligte Personen:

Wang, Yi-Jing [VerfasserIn]
Zhao, Pan [VerfasserIn]
Sui, Bing-Dong [VerfasserIn]
Liu, Nu [VerfasserIn]
Hu, Cheng-Hu [VerfasserIn]
Chen, Ji [VerfasserIn]
Zheng, Chen-Xi [VerfasserIn]
Liu, An-Qi [VerfasserIn]
Xuan, Kun [VerfasserIn]
Pan, Ya-Ping [VerfasserIn]
Jin, Yan [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Q369O8926L
Research Support, Non-U.S. Gov't
Resveratrol

Anmerkungen:

Date Completed 28.03.2019

Date Revised 06.03.2020

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s12276-018-0109-y

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM286024233