Identification and localization of telocyte-like cells in human umbilical cord stroma

Human umbilical cord (hUC) connective tissue, known as Wharton's jelly, contains multipotent stromal cells (MSCs). Despite being considered the primary source of MSCs for regenerative purposes, hUC is one of the least studied fetal tissues. We conducted a detailed examination of normal hUCs (n = 16) and identified telocyte-like cells (TLCs) exhibiting both structural and phenotypical features similar to telocytes previously described in various tissues, including the placenta. TLCs were found to be concentrated around intervascular stromal clefts in the UC. These cells had thin, elongated bipolar cell bodies (ninefold higher in length/width ratio compared to MSCs), distinguishing them from the well-defined MSCs, which display abundant ER-Golgi systems and high collagen production. We confirmed the presence of TLCs with marker expression patterns including F-actin, vimentin, α-SMA, α-actinin, caveolin-1⁺, c-Kit⁺, PDGFR-α⁺, CD34^-, CD73⁺, CD90⁺, and CD105⁺, reflecting a distinct stromal identity, either adjacent to MSCs or possibly originating from them. Isolation, culture, and immunocytochemical labeling further confirmed the presence of TLCs, highlighting the diverse nature of hUC cell cultures. These two cell types (TLCs and MSCs) were observed in contact with each other or within their respective populations. Each of the methods used in this study contributed to the identification of these cells, but none alone was enough to definitively characterize them. The findings conclusively demonstrate the existence of TLCs in the hUC. This provides significant new evidence regarding the cellular heterogeneity of the stem cell niche and suggests a potential role for TLCs in the stromal network of this tissue.