Bisphenol A and 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin at non‐cytotoxic doses alter the differentiation potential and cell function of rat adipose‐stem cells

Abstract

The possibility of chemical contamination is an important issue to consider when designing a cell therapy strategy. Both bisphenol A (BPA) and 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) are among the most environmentally relevant endocrine disrupting chemicals (EDCs, compounds with a high affinity for adipose tissue) recently studied. Adipose‐derived stem cells (ASCs) are mesenchymal stromal cells (MSCs) obtained from adipose tissue widely used in regenerative medicine to prevent and treat diseases in several tissues and organs. Although the experimental use of tissue‐engineered constructs requires careful analysis for approval and implantation, there has been a recent increase in the number of approved clinical trials for this promising strategy. This study aimed to evaluate cell viability, apoptosis, DNA damage, and the adipogenic or osteogenic differentiation potential of rat adipose‐derived stem cells (rASCs) exposed to previously established non‐cytotoxic doses of BPA and TCDD in vitro. Results demonstrated that 10 μM of BPA and 10 nM of TCDD were able to significantly reduce cell viability, while all exposure levels resulted in DNA damage, although did not increase the apoptosis rate. According to the analysis of adipogenic differentiation, 1 μM of BPA induced the significant formation of oil droplets, suggesting an increased adipocyte differentiation, while both 10 μM of BPA and 10 nM of TCDD decreased adipocyte differentiation. Osteogenic differentiation did not differ among the treatments. As such, BPA and TCDD in the concentrations tested can modify important processes in rASCs such as cell viability, adipogenic differentiation, and DNA damage. Together, these findings prove that EDCs play an important role as contaminants, putatively interfering in cell differentiation and thus impairing the therapeutic use of ASCs.

Bisphenol-A (BPA) Exposure as a Risk Factor for Non-Communicable Diseases

“…However, they are more prominent in bone marrow [71]. Recently, MSCs have been discovered to represent potential target cells for BPA [72,73]. The proadipogenic effect of BPA is widely reported.…”

Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures

“…Furthermore, pollutants have been shown to impact stem cell function [164][165][166][167][168][169][170][171][172][173][174]. Pesticides, tobacco smoke, and heavy metals have been identified as disruptors of stem cell homeostasis, leading to impaired regenerative capacity and tissue repair.…”

Current Evidence on Bisphenol A Exposure and the Molecular Mechanism Involved in Related Pathological Conditions

“…Moreover, BPA induces intestinal oxidative stress and reduces antioxidants by decreasing the expression of SOD, GPx, CAT, and T-AOC. Lastly, BPA has been described to activate the gut innate immune system, as demonstrated by the expression of TLR2, TLR4, MyD88, and NF-κB, as well as by increased levels of pro-inflammatory cytokines, such as IL-1β, IL-6, IL-8, and TNF-α [ 102 , 103 ].…”

“…MSCs have recently been discovered to represent potential target cells for BPA (see Figure 3 ). A recent study evaluated cell viability, apoptosis, DNA damage, and the differentiation potential of adipose tissue derived MSCs (ADSCs) exposed to non-cytotoxic doses of BPA and TCDD [ 102 ]. The authors concluded that even low doses of those EDCs were able to reduce cell viability and induce DNA damage, Moreover, adipogenic differentiation significantly varied according to BPA concentration.…”