Background Hypertrophic scar (HS) is a type of pathological scar that often affects the physical and mental quality of life of patients. In recent years, the research of mesenchymal stem cells has become more and more in-depth, and they have great potential in anti-scar therapy.

Objective To study the effect and possible mechanism of human umbilical cord mesenchymal stem cells (hUC-MSCs) on human hypertrophic scar fibroblasts (HSFBs) cultured in vitro.

Methods The hUC-MSCs cultured in vitro and human HSFBs were divided into three groups according to the proportion of inoculated cells: 0.5:1, 1:1 and 2:1. In addition, the control group inoculated with HSFBs only, the transforming growth factor beta 1 (TGF-β1) intervention HSFBs group (TGF-β1 concentration was 5 ng/mL) and the TGF-β1 and hUC-MSCs co-intervention group (ratio of hUC-MSCs to HSFBs was 1:1) were set up. After a certain period of time, hypertrophic scar fibroblasts and their supernatant were taken from six groups, and the proliferation rate of fibroblasts was measured by CCK-8. The collagen content in supernatant of hypertrophic scar fibroblasts in each group was detected by hydroxyproline method. Fibroblast mobility was detected by scratch test. The transcription levels of TGF-β1, Smad3, COL-Ⅰ, COL-Ⅲ, PI3K and AKT in fibroblasts were detected by RT-qPCR.

Results Compared with the control group, the 0.5:1, 1:1, 2:1 groups could inhibit the proliferation of human hypertrophic scar fibroblasts (P<0.05), and the 1:1 group had the most obvious inhibitory effect on proliferation and could inhibit the collagen secretion of fibroblasts (P<0.05). There was no significant difference in cell migration between the 0.5:1, 1:1, 2:1 groups and the control group after 12 h (P>0.05), and the cell migration ability of the 1:1, 2:1 groups was weaker than that of the control group and the 0.5:1 group after 24 h (P<0.05). The transcription levels of TGF-β1, Smad3, COL-Ⅰ and COL-Ⅲ in 0.5:1, 1:1 and 2:1 groups were lower than those in control group (P<0.05). The PI3K transcription level in 0.5:1 group was lower than that in the control group (P<0.05). There was no significant difference in the transcription level of AKT among the control group and the 0.5:1, 1:1 and 2:1 groups (P>0.05). Compared with the control group, TGF-β1 intervention group could promote the proliferation of hypertrophic scar fibroblasts (P<0.01), the collagen secretion (P<0.01), and the cell migration (P<0.05). The transcription levels of TGF-β1, Smad3, COL-Ⅰ, COL-Ⅲ, PI3K and AKT were also increased (P<0.01), hUC-MSCs intervention could inhibit the effects of TGF-β1 on promoting proliferation, collagen secretion, cell migration, and transcription (P<0.01).

Conclusion hUC-MSCs may inhibit the proliferation, migration and collagen synthesis of HSFBs through paracrine pathway, and inhibit TGF-β1/Smad3 and PI3K/AKT signaling pathways, thus playing a role in resisting TGF-β1 and promoting fibrosis.