Antiphotoaging Effect of Conditioned Medium of Dedifferentiated Adipocytes on Skin In Vivo and In Vitro: A Mechanistic Study

Abstract

Photoaging of skin occurs partially due to decreased synthesis and increased degradation of dermal collagen. Antiphotoaging therapy aims to counteract these effects. This study aimed to investigate whether secretory factors from dedifferentiated adipocytes (DAs) could alleviate photoaging in human dermal fibroblasts (HDFs) and in mice and to clarify the underlying mechanism. DAs were acquired and verified based on cellular biomarkers and multilineage differentiation potential. The concentrations of several cytokines in conditioned medium from DAs (DA-CM) were determined. In vivo pathological changes, collagen types I and III, and matrix metalloproteinase (MMP)-1 and -3 were evaluated following the injection of 10-fold concentrated DA-CM into photoaged mice. In vitro, the effect of DA-CM on stress-induced premature senescence in HDFs was investigated by 5-ethynyl-2¢-deoxyuridine (EdU) staining and b-galactosidase staining. The influence of DA-CM and transforming growth factor-b 1 (TGF-b 1 ) on the secretion of collagen types I and III, MMP-1, and MMP-3 in HDFs was evaluated by ELISA. In vivo, we found that subcutaneously injected 10-fold concentrated DA-CM increased the expression of collagen types I and III. In vitro, DA-CM clearly mitigated the decreased cell proliferation and delayed the senescence status in HDFs induced by ultraviolet B (UVB). HDFs treated with DA-CM exhibited higher collagen types I and III secretion and significantly lower MMP-1 and MMP-3 secretion. The TGF-b 1 -neutralizing antibody could partially reduce the recovery effect. Our results suggest that DAs may be useful for aging skin and their effects are mainly due to secreted factors, especially TGF-b 1 , which stimulate collagen synthesis and alleviate collagen degradation in HDFs.

Dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hSDF-1α expression participates in neural restoration in hypoxic-ischemic brain damage rats

“… 21 Dedifferentiated adipocytes may participate in functional regulation in the form of secretion by reprogramming cytokine expression (especially TGF-β1). 22 , 23 In this study, we utilized a whole-gene expression profiling array to explore the genes differentially expressed in the process of dedifferentiation. Overall, 693 genes were differentially expressed between the two groups, and hSDF-1α was the most differentially expressed gene between De-hUC-MSCs and hUC-MSCs.…”

The Paracrine Effect of Adipose-Derived Stem Cells Orchestrates Competition between Different Damaged Dermal Fibroblasts to Repair UVB-Induced Skin Aging

“…Another kind of adipose-derived cells that showed stem cell characterization is dedifferentiated adipocyte (DFAT), which has the proliferative ability, lineage redifferentiation potential, and pluripotent features [ 37 ]. Xu et al study showed that DFAT is also useful for photoaging skin due to secreting TGF- β 1 [ 38 ]. TGF- β 1 plays an important role in both ASCs and DFAT antiphotoaging effect.…”

The Ability of Conditioned Media From Stem Cells to Repair Vocal Fold Injuries

“…The concentration technique using an ultrafiltration unit with a 3‐kDa cutoff could be another limitation. Several studies have applied a technique for concentrating CM using ultrafiltration units . Most materials in CM, such as growth factors, cytokines, hormones, and genetic materials, could be concentrated.…”

“…Several studies have applied a technique for concentrating CM using ultrafiltration units. 16,32,33 Most materials in CM, such as growth factors, cytokines, hormones, and genetic materials, could be concentrated. However, materials under the 3-kDa cutoff, such as amino acids and nucleotides, were removed and not concentrated.…”