CD146 controls the quality of clinical grade mesenchymal stem cells from human dental pulp

Abstract

Background Human mesenchymal stem cells from dental pulp (hMSC-DP), including dental pulp stem cells from permanent teeth and exfoliated deciduous teeth, possess unique MSC characteristics such as expression of specific surface molecules and a high proliferation rate. Since hMSC-DP have been applied in numerous clinical studies, it is necessary to establish criteria to evaluate their potency for cell-based therapies. Methods We compared stem cell properties of hMSC-DP at passages 5, 10 and 20 under serum (SE) and serum-free (SF) culture conditions. Cell morphology, proliferation capacity, chromosomal stability, surface phenotypic profiles, differentiation and immunoregulation ability were evaluated. In addition, we assessed surface molecule that regulates hMSC-DP proliferation and immunomodulation. Results hMSC-DP exhibited a decrease in proliferation rate and differentiation potential, as well as a reduced expression of CD146 when cultured under continuous passage conditions. SF culture conditions failed to alter surface marker expression, chromosome stability or proliferation rate when compared to SE culture. SF-cultured hMSC-DP were able to differentiate into osteogenic, adipogenic and neural cells, and displayed the capacity to regulate immune responses. Notably, the expression level of CD146 showed a positive correlation with proliferation, differentiation, and immunomodulation, suggesting that CD146 can serve as a surface molecule to evaluate the potency of hMSC-DP. Mechanistically, we found that CD146 regulates proliferation and immunomodulation of hMSC-DP through the ERK/p-ERK pathway. Conclusion This study indicates that SF-cultured hMSC-DP are appropriate for producing clinical-grade cells. CD146 is a functional surface molecule to assess the potency of hMSC-DP.

Effect of Human Platelet Lysate as Cultivation Nutrient Supplement on Human Natal Dental Pulp Stem Cell In Vitro Expansion

“…Higher expression of CD105 might be explained by the fact that hPL is rich in several growth factors, including insulin-like growth factor 1 (IGF-1), transforming growth factor-beta (TGF-β1, TGF-β2). Ma et al concluded that the expression level of CD146 showed a positive correlation with proliferation, differentiation, and immunomodulation, suggesting that CD146 can serve as a surface molecule to evaluate the potency of human dental pulp stem cells cultivated in the serum-free medium [ 51 ]. To summarize all the above, hNDP-SCs seem more affected by changes in serum-free growth medium than other mesenchymal stem cells, and hPL keeps hNDP-SCs less differentiated and prepared for wider differentiation into mature cells lines.…”

A New Target of Dental Pulp-Derived Stem Cell-Based Therapy on Recipient Bone Marrow Niche in Systemic Lupus Erythematosus

“…Indeed, the clinical application of hDPSCs has started in dental pulp regeneration of injured teeth [ 32 ]. Recently, quality-controlled clinical-grade hDPSCs were manufactured for regenerative medicine applications [ 33 , 34 ].…”

Odontogenic MSC Heterogeneity: Challenges and Opportunities for Regenerative Medicine

“…CD146 is usually coexpressed with CD73, CD90, CD105, and CD44 on pericytes located outside of capillaries and microvessels in various tissues, such as the muscles, adipose tissue, BM and placenta ( Crisan et al, 2008 ). Several studies suggest that CD146 identifies MSCs with multidirectional differentiation potential ( Ma et al, 2021 ). Compared with CD146 - cells, CD146 + cells showed the potential to differentiate into adipocytes, chondrocytes, and osteoblasts, while CD146 - cells did not ( Baksh et al, 2007 ).…”