Mesenchymal Stem Cell Secretome for Dermatology Application: A Review

Figures & data

Table 1 Secretome Test Objects for Skin Application

No.	Biology Activity	Test Object	Testing	Ref
1.	Cutaneous wound	Human foreskin fibroblasts (HFFs)	In vitro	[^Citation14]
		Human immortalised keratinocytes (HaCaTs)	In vitro	[^Citation4,Citation5]
		Human dermal microvascular endothelial cells (HDMECs)	In vitro	[^Citation14]
		Human dermal fibroblasts (HDFs)	In vitro	[^Citation8,Citation15]
		Human endothelial cell	In vitro	[^Citation8]
		Human umbilical vein endothelial cells (HUVECs)	In vitro	[^Citation16]
		L929 Fibroblast	In vitro	[^Citation5]
		Wistar rats	In vivo	[^Citation17,Citation18]
		C57BL/6J mice	In vivo	[^Citation19]
		Lepr^db/db mice	In vivo	[^Citation20]
		Porcine models/ pigs	In vivo	[^Citation21]
		Rabbit ear	In vivo	[^Citation22]
		Female SCID Mice 8–9 weeks	In vivo	[^Citation4]
		Male volunteers	Clinic Phase 1	[^Citation23]
2.	Photoprotection	Human dermal fibroblasts (HDFs)	In vitro	[^Citation24,Citation25]
		Normal human dermal fibroblast (NHDF)	In vitro	[^Citation26]
		Human dermal fibroblast (HFF-1)	In vitro	[^Citation27]
		Human immortalized keratinocytes (HaCaTs)	In vitro	[^Citation28]
		NIH-3T3 cell	In vitro	[^Citation29]
		Nude mice	In vivo	[^Citation24,Citation28]
		Human Skin	Clinical test	[^Citation30]
3.	Hair Growth	Human follicle dermal papilla cells (HFDPCs)	In vitro	[^Citation31^–^Citation33]
		Human epithelial keratinocytes (HEKs)	In vitro	[^Citation31]
		Outer root sheath cells (ORC)	In vitro	[^Citation34]
		C3H/NeH mice	In vivo	[^Citation31,Citation34]
		C57BL/6 mice	In vivo	[^Citation33,Citation35]
		Nude mice	In vivo	[^Citation32]
4.	Psoriasis	Wistar rats	In vivo	[^Citation36]
5	Other (antimicrobial)	Rats	In vivo	[^Citation37]

Figure 1 Flowchart of the article collection.

Table 2 Potential Effect of Secretome in Skin Applications

No.	Application	Source and Kind of Secretome	Signaling and Bioactive Molecules Involved	Effects	Ref
1.	Cutaneous wound	ADSC-CM	EGF, bFGF, HGF	Increased proliferation and cell migration, angiogenesis and vascularization	[^Citation2]
			VEGF, IL-6, EGF, uPAR, MCP-3, G-CSF, and Tie-2,	Promoted angiogenesis (CD31), epithelialization, and decreased wound area	[^Citation52]
			Tnc, Dcn and EGFR.	Accelerated re- epithelialization and deposition of collagen	[^Citation53]
		MAPC-CM	HGF, VEGF	Increased keratinocytes, fibroblasts, and endothelial cells as well as cell proliferation	[^Citation14]
		WJSC-CM	EGF	Enhanced proliferation and cell migration as well angiogenesis	[^Citation54]
		BMSC-CM	VEGF and angiopoietin-1	Stimulated cell proliferation, and decreased level of granulation tissue and fibrous	[^Citation39,Citation54]
			EGF, bFGF,	Increased proliferation and cell migration as well as fibroblast in diabetic wounds	[^Citation15]
		PBMCs-CM	CD31+, α-SMA+	Increased the thickness of epidermis, angiogenesis, and reduced the level of mast cells	[^Citation17,Citation19^–^Citation21]
		UCSC-CM/ UCX^®	HGF, IL-6, FGF-2, TGF-β1, G-CSF, VEFG-A	Improved angiogenesis, elastin formation capillary maturation and vascularity level,	[^Citation17,Citation55]
		DPSC-CM	Angiogenin, EGF, bFGF, IL-6, IL 8, PDGF-AA, VEGF, HGF, GM-CSF	Increased migration and proliferation and angiogenesis cell	[^Citation56]
		DPFi-CM	sAXL and CCL19	Enhanced re-epithelialization and wound closure	[^Citation57]
		Fetal dermal cells-CM	VEGF, IL-8, HGF, CXCL-12, CCL-2, CXCL1	Improved angiogenesis, re- epithelialization and neovascularization	[^Citation16]
2.	Photoprotection	BMSC-CM	VEGF, TGF β	Stimulated procollagen synthesis, suppressed the production of MMP1 and CPD formation	[^Citation24]
		ADSC-CM	TGF β-1 PDGF-AA	Increased procollagen synthesis, inhibited MMP1 and MMP9 production, sub G1 phase and cellular apoptosis as well as enhanced skin hydration effect and, improved mRNA expression	[^Citation25,Citation28,Citation58^–^Citation60]
		UCSC-Exo	↓NRF2 signaling	Suppressed ROS accumulation and DNA damage	[^Citation61]
		EPC-CM	IL-6, Angiopoietin-1, TIMP-1 and TIMP-2	Stimulated proliferation and collagen production and inhibited ROS formation	[^Citation26]
3.	Hair Growth/ Alopecia	ADSC-CM	Increase level of IGFBP-1, IGFBP-2, M-CSF, M-CSF R, PDGF R-β, and VEGF	Enhanced proliferation of HFDPCs and HEKs cell	[^Citation31]
		KCs-CM	VEGF, BMP2, TGF-b1, IL-6, IGFBP-2 and 5, PDGF-AA	Improved proliferation of dermal papilla (DP) cell	[^Citation32,Citation34]
		AF-MSC-CM	IGF, PDGF, bFGF, and Wnt7a	Accelerated telogen to anagen transition in hair follicles (HF) and increased HF density	[^Citation33]
		BMSC-EV	AKT phosphorylation, Bcl2, VEGF and IGF-1	Accelerated the conversion of telogen to anagen	[^Citation62]
		DPC-CM	SDF1, MMP3 and biglycan, LTBP1	Induced regeneration of hair follicle	[^Citation63]
4.	Psoriasis	Skin mice	IL1B, IL10, F4/80, CD11C	Inhibited dendritic cells (DC) and IL-17	[^Citation64]
5.	Antimicrobial activity	ADSC-CM	LL-37	Inhibited the growth of S. aureus	[^Citation65]

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