New research has discovered how dental tissue stem cells retain their growth and immunomodulatory characteristics, even in older donors, offering exciting opportunities for stem cell therapy.
With their multilineage differentiation abilities and prompt availability in clinically relevant quantities, it is no surprise that mesenchymal stem cells (MSCs) are at the forefront of stem cell research. However, various studies demonstrated the deleterious effects of natural aging on the quality of MSCs, hindering their use for autologous transplantation in older patients.
The study, published in Science Advances, investigated the effect of aging on the biological properties of gingival mesenchymal stem cells (GMSCs). Gingival are dental tissues containing stem cells, offering great potential use in regenerative medicine.
The new research was led by a team from the Institute of Bioinformatics and Biotechnology. The authors said, “Our data shows that increased donor age does not deteriorate GMSCs in terms of quantity and quality.”
Firstly, comparative analysis of a mean transit time (MTT) assay showed no significant proliferative differences between GMSCs cultured from different age groups.
The study found that proliferation rates of GMSCs in younger donors expanded rapidly and underwent faster in-vitro replicative senescence. Meanwhile, GMCSCs from older patients expressed higher levels of p53, a protein found to act as a tumour suppressor.
The authors reported, “The high levels of p53 are correlated to the maintenance of genomic integrity by suppressing dysplastic proliferation, and their replicative abilities of GMSCs in older donors are compensated by the expression of growth factor receptors.”
The results suggested that GMSCs can enhance proliferation despite the stressful conditions that build up with age, to facilitate a healthy stem cell pool in gingival tissue.
The researchers induced cultures of GMSCs of ranging age groups for adipogenic, osteogenic and neurogenic differentiation. The team found that older differentiated GMSCs displayed a reduction in differentiated adipocytes. A reduction in osteogenic cultures were also observed by a decrease calcium phosphate mineralisation.
“It seemed their ability to synthesize matrix proteins and to incorporate phosphate within the matrix at later stages of differentiation declines with age,” the authors noted.
However, the neurogenic differentiation ability of GMSCs stayed the same amongst all age groups. The team proposed that this could be because gingival tissues originate from the neural crest and noted that this could explain GMSC’s skew in maturation towards the neuronal lineage.
Immunoregulatory and immunosuppressive effects of GMSCs
The team administered GMSCs into a lipopolysaccharide (LPS)- induced acute lung injury (ALI) mouse model. Here, GMSCs from all age groups showed a downregulation in gene expression of pro-inflammatory cytokines such as TNFα and TNFβ. Immunosuppressive abilities, independent of age, were further highlighted by histopathological analysis. Administration of GMSCs in LPS-induced ALI mice resulted in the reduction of infiltrated neutrophils in both alveolar and interstitial spaces; reduced thrombosis and promoted structural improvements across all age groups.
GMSCs offer a unique opportunity into potential treatment strategies for neuronal regeneration therapy due to their skewed neurogenic differentiation.
The authors said, “The coronavirus disease 2019 pandemic has awakened the world to great consequences of biological risk and brought our attention toward the most vulnerable population of elderly individuals.”
The study has opened doors to utilising gingival tissue as a source of mesenchymal stem cells for autologous transplants in older patients.
Written by Harry Yuen, Science Writer Intern
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