Abstract

Endocrine-disrupting chemicals (EDCs) are prevalent in the environment, and epidemiologic studies have suggested that human exposure is linked to chronic diseases, such as obesity and diabetes. In vitro experiments have further demonstrated that EDCs promote changes in mesenchymal stem cells (MSCs), leading to increases in adipogenic differentiation, decreases in osteogenic differentiation, activation of pro-inflammatory cytokines, increases in oxidative stress, and epigenetic changes. Studies have also shown alteration in trophic factor production, differentiation ability, and immunomodulatory capacity of MSCs, which have significant implications to the current studies exploring MSCs for tissue engineering and regenerative medicine applications and the treatment of inflammatory conditions. Thus, the consideration of the effects of EDCs on MSCs is vital when determining potential therapeutic uses of MSCs, as increased exposure to EDCs may cause MSCs to be less effective therapeutically. This review focuses on the adipogenic and osteogenic differentiation effects of EDCs as these are most relevant to the therapeutic uses of MSCs in tissue engineering, regenerative medicine, and inflammatory conditions. This review will highlight the effects of EDCs, including organophosphates, plasticizers, industrial surfactants, coolants, and lubricants, on MSC biology.

Highlights

  • Reviewed by: Sylvie Babajko, Centre de Recherche des Cordeliers, France Ren-Shan Ge, Wenzhou Medical University, China

  • This review focuses on the adipogenic and osteogenic differentiation effects of endocrine-disrupting chemical (EDC) as these are most relevant to the therapeutic uses of mesenchymal stem cell (MSC) in tissue engineering, regenerative medicine, and inflammatory conditions

  • In the context of tissue engineering for critical-sized defects and fractures, tissue scaffolds may be seeded with MSCs that have been exposed to EDCs, and the EDC exposure may impair the capacity of the MSCs for osteogenic differentiation

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Summary

EDC Effects in MSCs

Mesenchymal stem cells are multipotent cells that maintain homeostasis in the human body by regeneration and repair of damaged and aged tissues. Scaffolds provide a three-dimensional structure to mechanically stimulate MSCs to undergo osteogenic differentiation or to secrete paracrine factors [10,11,12,13] Together, these studies suggest that MSCs may have potential applications in the repair of fractures and bony defects [10,11,12,13]. MSCs suppress T-cell proliferation and cytotoxic potential, inhibit maturation and T-cell stimulation by dendritic cells, inhibit B-cell proliferation and differentiation, reduce production of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), and enhance production of anti-inflammatory cytokines, such as interleukin 10 (IL-10) and interleukin 4 [8, 9, 14,15,16,17,18]. MSCs may have broad therapeutic uses in the prevention and treatment of diseases with pro-inflammatory pathogenesis

ENDOCRINE DISRUPTORS
EFFECT OF ENDOCRINE DISRUPTORS ON MSCs AND MSC LINEAGES
OXIDATIVE STRESS
DEVELOPMENT OF EPIGENETIC CHANGES
Effect on Tissue Engineering
Effect on Immunomodulatory Capacity
CONCLUSION
AUTHOR CONTRIBUTIONS
Full Text
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