Human skin dermis-derived fibroblasts are a kind of functional mesenchymal stromal cells: judgements from surface markers, biological characteristics, to therapeutic efficacy

Abstract

Background Human mesenchymal stromal cells (MSCs) have been widely advocated to clinical use. Human skin dermis-derived fibroblasts shared similar cellular morphology and biological characteristics to MSCs, while it still keeps elusive whether fibroblasts are functionally equivalent to MSCs for therapeutic use. Methods We isolated various fibroblasts derived from human foreskins (HFFs) and human double-fold eyelids (HDF) and MSCs derived from human umbilical cords (UC-MSCs), and then comprehensively investigated their similarities and differences in morphology, surface markers, immunoregulation, multilineage differentiation, transcriptome sequencing, and metabolomics, and therapeutic efficacies in treating 2,4,6-Trinitrobenzenesulfonic acid (TNBS) induced colitis and carbontetrachloride (CCL4) induced liver fibrosis. Results Fibroblasts and UC-MSCs shared similar surface markers, strong multilineage differentiation capacity, ability of inhibiting Th1/Th17 differentiation and promoting Treg differentiation in vitro, great similarities in mRNA expression profile and metabolites, and nearly equivalent therapeutic efficacy on TNBS-induced colitis and CCL4-induced hepatic fibrosis. Conclusion Human skin dermis-derived fibroblasts were a kind of functional MSCs with functionally equivalent therapeutic efficacy in treating specific complications, indicating fibroblasts potentially had the same lineage hierarchy of origin as MSCs and had a remarkable potential as an alternative to MSCs in the treatment of a variety of diseases.

Fibroblast‐derived growth factors and exosomes as cosmeceuticals

“…Here we summarized the role of FB‐derived secretome in rejuvenation of aged skin phenotype and provided early indication of clinical activity attributed to the presence of active exosomes in the secretome. Dermal FBs are shown to have biological activity similar to MSCs in treating specific complications and have a remarkable potential as an alternative to MSCs in the treatment of a variety of skin diseases 21 . While there are many recent publications that describe the role of secretome and exosomes from MSCs and platelets in skin rejuvenation, FB‐derived secretome is still a relatively under‐appreciated source of rejuvenating exosomes.…”

“…20 Human foreskin FB and umbilical cord MSCs (UC-MSC) share similar surface markers, strong multilineage differentiation capacity and similarities in mRNA expression profile and metabolites. 21 There is increasing evidence that FB can also differentiate into other cell types including cells of adipogenic and osteogenic lineages. 22 Dermal FB may act as functional MSCs in skin, are easily harvested in large quantities and are significantly more accessible than other forms of MSCs.…”

“…22 Dermal FB may act as functional MSCs in skin, are easily harvested in large quantities and are significantly more accessible than other forms of MSCs. 21 All these factors along with over 20 years of clinical use 23 in topical skincare make dermal FB ideal for larger scale production of secretome and exosomes. wrinkling after 60 days of topical use.…”

“…FB‐derived growth factors or secretome currently account for the largest number of published clinical studies on use of topical growth factors for skin rejuvenation 20 . Human foreskin FB and umbilical cord MSCs (UC‐MSC) share similar surface markers, strong multilineage differentiation capacity and similarities in mRNA expression profile and metabolites 21 . There is increasing evidence that FB can also differentiate into other cell types including cells of adipogenic and osteogenic lineages 22 .…”

“…There is increasing evidence that FB can also differentiate into other cell types including cells of adipogenic and osteogenic lineages 22 . Dermal FB may act as functional MSCs in skin, are easily harvested in large quantities and are significantly more accessible than other forms of MSCs 21 . All these factors along with over 20 years of clinical use 23 in topical skincare make dermal FB ideal for larger scale production of secretome and exosomes.…”