Table 2 Therapeutic uses of ADSC-CM

[29]

Eun Young Lee

HDFs were incubated with norCM or hypoCM

Two circular full-thickness wounds of 8 mm diameter were created on the backs of the mice.

1. HypoCM promotes HDFs migration and type I collagen secretion and significantly reduced the size of the wound area and depth

2. The wound-healing effect of hypoCM was significantly reduced by the addition of the antibodies of both VEGF and bFGF

[30]

Denise R. Cooper

Co-culture of ADSC-CM with HDF

Rat model of ischemic wound healing

1. ADSC-CM promotes HDF migration and accelerates closure of ischemic wounds.

2. There was no difference between unconditioned media or ADSC-CM for non-ischemic wounds.

[31]

Talita Stessuk

Co-culture of ADSC-CM and PRP with fibroblasts and keratinocytes

1.PRP and ADSC have therapeutic potential for healing and re-epithelialization of chronic wounds.

[15]

Jiajia Zhao

Co-culture of ADSC-CM with HDF

1. EGF, PDGF-AA, VEGF, and bFGF had high concentrations in ADSC-CM.

2. The migration of skin fibroblasts could be significantly stimulated by VEGF, bFGF, and PDGF-AA, and the proliferation could be significantly stimulated by bFGF and EGF in ASC-CM.

[32]

Min Ho Kim

The HaCaT cells and HDF were incubated with the ADSC-CM-2D or ADSC-CM-3D

1. ADSC-CM-3D has a more significant effect on the proliferation and migration of fibroblasts and keratinocytes, the reason may be related to galectin1 expression only in 3D cultured ADSC

[33]

Chengliang Deng

Fibroblast and keratinocyte were cultured in Gel-CM, SVF-CM, or serum-free medium

Full-thickness skin wound of diabetic rats

1. Gel-CM promoted the proliferation and migration of fibroblasts & keratinocytes and increased collagen synthesis in fibroblasts

2. The wound-healing rate in the Gel-CM-treated group was significantly higher than that in the SVF-CM-treated group at all timepoints.

[34]

Chengliang Deng

Fibroblasts and keratinocytes were cultured in Gel-CM, Adi-CM, and SVF-CM or serum-free medium.

BALB/c nude mice wound model

1. Gel-CM-treated group achieved complete wound healing, whereas the other groups still had unhealed wounds

2. Higher expression of bFGF, EGF, and TGF-b in Gel-CM than in other two CMs and a significantly higher expression of VEGF in Gel-CM than in SVF-CM

[35]

Bing-rong Zhou

Twenty-two subjects with Fitzpatrick phototypes III and IV, aged 24 to 50

1. ADSC-CM + FxCR can increase skin elasticity, improve skin surface roughness, and reduce transepidermal water loss, reduce pigmentation after laser

2. ADSC-CM increased dermal collagen density, elastin density, and arranged them in order.

[36]

Xi Wang

30 female volunteers, skin type III and IV, aged 40 to 63

1. Microneedles + ADSC-CM can improve skin roughness, reduce melanin content, increase skin brightness, gloss, elasticity, and anti-wrinkle effects

[16]

Woo-Chan Son

Co-culture of ADSC-CM with UV irradiation of HDF

1. MMP-1 expression was significantly increased in retinoic acid-treated group and both 50 and 100% AdMSC-CM

2. Type 1 procollagen level was significantly increased in TGF-β1-treated group and both 50 and 100% AdMSC-CM treated group

[17]

Shu Guo

Co-culture of different senescent HDF with ADSC-CM before UVA irradiation

1. ADSC-CM pretreatment was significantly reduced HDF aging rate.

2. ADSC-CM up-regulated the expression of type I, type III collagen and elastin, and downregulated the expression of MMP-1 and MMP-9 mRNA

[37]

Lu Li

HaCaTs and NHDFs were irradiated with UV and cultured with 50% and 100%ADSC-CM

1. Both 50% and 100% ADSC-CM treatment can reduce ROS levels

2. ADSC-CM reduces the production of MMP-1 and the secretion of IL-6 by down-regulating UVB-induced MAPK and TGF-β/Smad signaling pathways 3.100% ADSC-CM treatment, the mRNA expression of procollagen type I was gradually increased in HaCaTs and NHDFs

[38]

Xiuxia Wang

Keloid fibroblasts were cultured in ADSC-CM

1. ADSC-CM reduced the ECM-related gene expression in KFs and inhibited cell proliferation and migration

2. ADSC-CM depleted CD31+/CD34+ vessels and reduced collagen deposition

[39]

Qi Zhang

Rabbit ear hypertrophic scar model

1. Both ADSC and ADSCs-CM treatments reduce scar hypertrophy 2. ADSCs were more effective than ADSCs-CM in reducing hypertrophic scars

[40]

Yan Li

HS tissues were cultured with ADSC-CM in the presence of a p38 inhibitor and activator

BALB/c mouse excisional model

1. ADSC-CM decreased the expression of Col1, Col3, and α-SMA in HSFs and suppressed collagen deposition in cultured HS tissues

2. ADSC-CM suppressed scar formation through the inhibition of the p38/MAPK signaling pathway in HSFs in vitro and the anti-fibrosis effect of ADSC-CM was mediated by the p38/MAPK signaling pathway in BALB/c mouse excisional models in vivo

[41]

Junnan Chen

HSFs were cultured in CFSC-CM or control medium

1. CFSC-CM inhibited HSF proliferation and migration

2. CFSC-CM inhibited HSF ECM protein expression

[18]

Ji Ma

HSFs were treated with ADSCs-CM.

1. HGF secreted by ADSC shows anti-fibrotic effect and ADSC-CM attenuates collagen production in HSFs

2. High concentrations of ADSC-CM can inhibit the Col1/Col3 ratio, reduce TIMP-1 levels, and up-regulates MMP-1 expression

[42]

Xing Shan

Adult male rabbit ears acne vulgaris scar model

1. Almost all acne scars were cured after ADSC+CM injection in the rabbit ear acne scar model.

2. ADSC + CM reduces levels of TNF-α, IL-1α, MMP2, and keratin 16

[43]

Peng Hao

Co-culture of ADSC-CM and glutamate-induced neurons

1. ADSC-CM reduced glutamate-induced neuronal injury with a maximum protective effect at 50% CM and neuronal LDH release and trypsin-positive cells

2. ADSC-CM can rescue glutamate-induced neuronal energy depletion

[44]

Yu Jin Cho

HUVECs cultured in 1 ml EGM complete media supplemented ahADSC-CM

Rats MCAO model

1. Continuous infusion of ahADSC-CM can significantly improve functional and structural recovery after stroke

2. Continuous infusion of ahADSC-CM significantly reduced the number of TUNEL-positive cells and Iba1 / TUNEL-positive cells and increased the number of CD31 + microvessels

[19]

Xing Wei

Hypoxic-ischemic brain injury model in neonatal rats

1. AdSC-CM markedly attenuated both short-term and long-term effects of HI-induced brain damage and the deficit in spatial learning and memory associated with HI

2. IGF-1 and BDNF contained in ADSC-CM play an important role in the recovery of neuropathic injury and significantly reduce the long-term functional cognition and motor skills impairment of hypoxic-ischemic brain injury in rats

[45]

Hongyan Lu

HPAEC were treated with ADSC-CM

Mouse lipopolysaccharide-induced ARDS model

1. ADSC-CM-pretreated HPAEC displayed less severe changes in response to H2O2, with attenuated gap formation and ADSC-CM treatment markedly suppressed the LPS-induced protein increase 48 h post-injection. ADSC-CM leads to lung recruitment of neutrophils with a reduced potential for oxidative response.

2. The LPS-induced level of VEGF in BALF was markedly suppressed in ADSC-CM-treated mice

[46]

Anandharajan Rathinasabapathy

Mouse pulmonary hypertension model and pulmonary fibrosis model

1. ADSC-CM treatment arrest the progression of PH by improving ventricular dynamics and attenuating cardiac remodeling and improves the pulmonary vascular remodeling associated with PH

2. ADSC-CM can prevent the progression of PF in the BLEO model in a model of rat PF induced by bleomycin (BLEO)