Cholesterol 24S-Hydroxylase overexpression increases the lipid droplet formation of human umbilical cord mesenchymal stem cells but does not affect adipocyte differentiation.

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Dysregulation of the adipo-osteogenic differentiation balance of mesenchymal stem cells (MSCs), which are common progenitor cells of adipocytes and osteoblasts, has been associated with many pathophysiologic diseases, such as obesity, osteopenia, and several neurodegenerative disorders. Growing evidence suggests that lipid metabolism is crucial for maintaining stem cell homeostasis and cell differentiation, however, the detailed underlying mechanisms are largely unknown. In this study, we demonstrate that CYP46A1 genes are key determinants of MSC increasing lipid droplet formation. Brain cholesterol is synthesized in situ and cannot cross the blood-brain barrier: to be exported from the central nervous system into the blood circuit, excess cholesterol must be converted to 24S-hydroxycholesterol by the cholesterol 24-hydroxylase encoded by the CYP46A1 gene. To address this issue, we used an adenoassociated virus (AAV) gene transfer strategy to increase CYP46A1 expression in order to investigate the consequences on the human mesenchymal stem cell (hU-MSCs). CYP46A1 expression was assessed with Western blotting and quantitative reverse transcription PCR. We found that CYP46A1 expression was increased during adipogenesis, and treatment with exogenous CYP46A1 increased adipogenesis. Thus, we hypothesize that CYP46A1 overexpression in hU-MSCs would significantly enhance cholesterol t

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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