Different temporal dynamics of primary cilia formation and elongation during adipocyte differentiation in umbilical cord- and bone marrow-derived mesenchymal stem cells

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are considered a promising alternative to bone marrow-derived MSCs (BM-MSCs) due to their high proliferative capacity and non-invasive accessibility. While UC-MSCs exhibit osteogenic, chondrogenic, and myogenic differentiation potential comparable to BM-MSCs, their adipogenic differentiation is significantly delayed. To investigate the underlying mechanisms, we focused on primary cilia, sensory organelles that regulate key adipogenic signaling pathways, including the insulin-Akt axis. Under serum-starved, growth-arrest conditions, both UC-MSCs and BM-MSCs formed primary cilia at similar frequencies and lengths; however, under serum-fed, proliferative conditions, UC-MSCs showed a significantly lower frequency of ciliation. During adipogenesis, BM-MSCs exhibited early ciliogenesis and stable cilium length, whereas UC-MSCs displayed delayed ciliogenesis and developed significantly longer cilia after repeated induction cycles. Despite comparable ciliation frequency and longer cilia in UC-MSCs at later stages, insulin-induced Akt activation was reduced compared to BM-MSCs, suggesting that primary cilia in UC-MSCs may be less efficient in sensing insulin. These alterations in insulin signaling may contribute to the reduced adipogenic capacity observed in UC-MSCs.