Effects of conditioned medium obtained from human adipose-derived stem cells on skin inflammation

Fumiko Yano; Taiga Takeda; Takafumi Kurokawa; Toshiya Tsubaki; Ryota Chijimatsu; Keita Inoue; Shinsaku Tsuji; Sakae Tanaka; Taku Saito

doi:10.1016/j.reth.2022.03.009

Effects of conditioned medium obtained from human adipose-derived stem cells on skin inflammation

Regen Ther. 2022 Apr 16:20:72-77. doi: 10.1016/j.reth.2022.03.009. eCollection 2022 Jun.

Authors

Fumiko Yano^{1

2}, Taiga Takeda^{1

3}, Takafumi Kurokawa², Toshiya Tsubaki², Ryota Chijimatsu^{1

2}, Keita Inoue³, Shinsaku Tsuji³, Sakae Tanaka², Taku Saito²

Affiliations

¹ Bone and Cartilage Regenerative Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
² Sensory and Motor System Medicine, The Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
³ Avenue Cell Clinic, 3-18-16 #3F Minami-Aoyama, Minato-ku, Tokyo, 107-0062, Japan.

Abstract

Introduction: Cell therapy using adipose-derived mesenchymal stem cells (ASCs) is a promising avenue of regenerative medicine for the treatment of various diseases. It has been considered that ASCs exert their therapeutic effects through the secretion of multiple factors that are critical for tissue remodeling or the suppression of inflammation. Recently, conditioned medium (CM) from ASCs that contains a complex of secreted factors has received attention as a cost-effective alternative to cell therapy.

Methods: We investigated the effects of CM obtained from ASCs (ASCs-CM) using human dermal fibroblasts (hDFs) and human epidermal keratinocytes with or without interleukin (IL)-1β and examined mRNA levels of marker genes. We also examined alterations in cell proliferation and morphology of hDFs following treatment with ASCs-CM. We further investigated the effects of ASCs-CM treatment on prevention of skin inflammation using a mouse model.

Results: In hDFs and human epidermal keratinocytes, the ASCs-CM treatment suppressed pro-inflammatory factors and enhanced regenerative and remodeling factors with or without interleukin (IL)-1β exposure. The ASCs-CM treatment also enhanced cell proliferation of hDFs and prevented morphological changes in response to IL-1β exposure. Furthermore, in a mouse model of skin inflammation, treatment with ASCs-CM reduced the inflammatory reactions, including redness and thickness.

Conclusions: CM from ASCs may represent a potential alternative to ASC therapy for the treatment of inflammatory skin conditions.

Keywords: ASC therapy; Adipose-derived mesenchymal stem cells (ASCs); Conditioned medium (CM); Human dermal fibroblasts (hDFs); Interleukin (IL)-1β; Skin inflammation.