Table 3 In vitro studies evaluating the effect of FA on bone tissue formation
From: Effect of folic acid on animal models, cell cultures, and human oral clefts: a literature review
Author | Cell type | FA dose | Administration method | Conclusion | Authors’ judgement |
|---|---|---|---|---|---|
Xiao et al. 2006 [34] | Mouse embryonic palate MSC | 1–100 μg/mL | Directly applied to the cell-culture medium | Cell proliferation is FA dose-dependent. | FA promotes cell differentiation and could help prevent CLP. |
Herrmann et al. 2007 [35] | Human osteoblasts | 0–1000 μg/L | Directly applied to the cell-culture medium | Accumulation of HCY by decreasing concentrations of folate, vitamin B12, and B6 does not impact the activity of human osteoblasts. | Could not explain the effect of FA on the formation of CLP. |
Herrmann et al. 2007 [36] | Osteoclasts obtained from peripheral blood-MSC | 0–15 μg/L | Directly applied to the cell-culture medium | Cell cultures with low concentrations of FA, B12, and B6 demonstrate a significant increase in osteoclastic activity. Simultaneous deficiency of the three vitamins stimulates dentinal resorption and osteoclastic activity. | FA could help prevent the formation of CLP. |
Kobus et al. 2009 [38] | Fertile eggs of Gallus domesticus | 0.5 μg/0.25 μL | Injection into the yolk sac | High concentrations of FA alter neural cell differentiation in vitro. | Does not help in explaining the effect of FA on the formation of CLP. |
Ahmed et al. 2016 [37] | HTR-8/SVneo cells BeWo cells Human placenta tissue explants | 2–2000 ng/mL | Directly applied to the cell-culture medium | Treatment with excess FA (2000 ng/mL) resulted in reduced cellular viability in the villous trophoblast BeWo cell line and increased rates of proliferation in the HT8-8/SVneo extravillous trophoblast cell line. Deficient concentrations of FA (2 ng/mL) resulted in decreased cell viability and invasive capabilities of the HTR-8/ SVneo extravillous trophoblast cell line. | Supports the benefits of FA, which are not linked to CLP. |
Melo et al. 2016 [33] | Neural crest cells of mouse embryos | 0.45–90 μM | Directly on cell cultures. | High HCY concentration alters the morphogenesis of neural cells in mammals. The protective effect of folate is due to its ability to prevent HCY-induced teratogenesis. | FA could prevent HCY-induced CLP. |
Santos et al. 2017 [9] | Bone marrow MSC | 1–500 μg/mL | Hydroxyapatite particles loaded with FA. | Hydroxyapatite with FA particles can enhance the effect of hydroxyapatite on osteoblast differentiation. | FA promotes cell differentiation and could help prevent CLP. |