Adipose-derived stem cell-conditioned medium (ADSC-CM) has been widely studied and used as a stem cell-based cell-free therapy. Due to the explosion of scientific publications in this field, it is difficult to review all relevant publications systematically, not mention quantitively. In this study, we combined bibliometrics with the conventional review method to summarize, analyze, and visualize the characteristics of nearly all published articles related to ADSC-CM using CiteSpace—a bibliometrics software. We applied this software to quantitively and vividly show (a) annual publications and citations; (b) distributions and co-occurrence networks of countries/regions, authors, journals, and institutions; (c) keyword co-occurrence networks and clusters in different time periods; (d) cocitation networks of references; and (e) ongoing challenges and new topics in ADSC-CM. Altogether, we found that ADSC-CM is at a hot stage with an increasing number of publications and citations, extensive and close scientific collaborations, and dense cocited networks.
Impact statement
To our best knowledge, it is the first bibliometric and visualized review in the field of adipose-derived stem cell-conditioned medium (ADSC-CM). This review systematically and quantitatively revealed the developments, challenges, and emerging hot spots of ADSC-CM, providing a panoramic view to assist researchers to decide the direction of their future study in the fields of ADSCs and CM derived from stem cells.
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References
1.
Mohamed-AhmedS, FristadI, LieSA, et al.Adipose-derived and bone marrow mesenchymal stem cells: A donor-matched comparison. Stem Cell Res Ther, 2018; 9(1):168; doi: 10.1186/s13287-018-0914-1
2.
TobitaM, OrbayH, MizunoH. Adipose-derived stem cells: Current findings and future perspectives. Discov Med, 2011; 11(57):160–170.
3.
CaiY, LiJ, JiaC, et al.Therapeutic applications of adipose cell-free derivatives: A review. Stem Cell Res Ther, 2020; 11(1):312; doi: 10.1186/s13287-020-01831-3
4.
KapurSK, KatzAJ. Review of the adipose derived stem cell secretome. Biochimie, 2013; 95(12):2222–2228; doi: 10.1016/j.biochi.2013.06.001
5.
VizosoF, EiroN, CidS, et al.Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci, 2017; 18(9):1852; doi: 10.3390/ijms18091852
KimYS, AumJ, KimBH, et al.Therapeutic effect of three-dimensional cultured adipose-derived stem cell-conditioned medium in renal ischemia-reperfusion injury. Int J Stem Cells, 2023; 16(2):168–179; doi: 10.15283/ijsc22137
8.
ZhangX, HuM, PanK, et al.3D spheroid culture enhances the expression of antifibrotic factors in human adipose-derived MSCs and improves their therapeutic effects on hepatic fibrosis. Stem Cells Int, 2016; 2016:4626073; doi: 10.1155/2016/4626073
9.
ElshaerS, EvansW, PentecostM, et al.Adipose stem cells and their paracrine factors are therapeutic for early retinal complications of diabetes in the Ins2(Akita) mouse. Stem Cell Res Ther, 2018; 9:322; doi: 10.1186/s13287-018-1059-y
10.
PalomaresT, CorderoM, Bruzos-CidonC, et al.The neuroprotective effect of conditioned medium from human adipose-derived mesenchymal stem cells is impaired by n-acetyl cysteine supplementation. Mol Neurobiol, 2018; 55(1):13–25; doi: 10.1007/s12035-017-0714-0
11.
ChansaenrojA, YodmuangS, FerreiraJ. Trends in salivary gland tissue engineering: From stem cells to secretome and organoid bioprinting. Tissue Eng B Rev, 2021; 27(2):155–165; doi: 10.1089/ten.teb.2020.0149
12.
MeadB, LoganA, BerryM, et al.Paracrine-mediated neuroprotection and neuritogenesis of axotomised retinal ganglion cells by human dental pulp stem cells: Comparison with human bone marrow and adipose-derived mesenchymal stem cells. PLoS One, 2014; 9(10):e109305; doi: 10.1371/journal.pone.0109305
13.
EiróN, Sendon-LagoJ, SeoaneS, et al.Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells. Oncotarget, 2014; 5(21):10692–10708; doi: 10.18632/oncotarget.2530
14.
NinkovA, FrankJR, MaggioLA. Bibliometrics: Methods for studying academic publishing. Perspect Med Educ, 2021; 11(3):173–176; doi: 10.1007/S40037-021-00695-4
15.
KooM, LinS-C. An analysis of reporting practices in the top 100 cited health and medicine-related bibliometric studies from 2019 to 2021 based on a proposed guidelines. Heliyon, 2023; 9(6):e16780; doi: 10.1016/j.heliyon.2023.e16780
16.
Guaita MartínezJM, CarracedoP, Gorgues ComasD, et al.An analysis of the blockchain and COVID-19 research landscape using a bibliometric study. Sustainable Technol Entrepreneurship, 2022; 1(1):100006; doi: 10.1016/j.stae.2022.100006
17.
StrielkowskiW, SamoilikovaA, SmutkaL, et al.Dominant trends in intersectoral research on funding innovation in business companies: A bibliometric analysis approach. J Innovation Knowledge, 2022; 7(4):100271; doi: 10.1016/j.jik.2022.100271
18.
ChenC. Searching for intellectual turning points: Progressive knowledge domain visualization. Proc Natl Acad Sci USA, 2004; 101(Suppl_1):5303–5310; doi: 10.1073/pnas.0307513100
19.
SynnestvedtMB, ChenC, HolmesJH. CiteSpace II: Visualization and knowledge discovery in bibliographic databases. AMIA Annu Symp Proc, 2005; 2005:724–728.
ChoH, KimY, KimS, et al.Endogenous Wnt signaling promotes proliferation and suppresses osteogenic differentiation in human adipose derived stromal cells. Tissue Eng, 2006; 12(1):111–121; doi: 10.1089/ten.2006.12.111
22.
ParkB, JangK, SungJ, et al.Adipose-derived stem cells and their secretory factors as a promising therapy for skin aging. Dermatol Surg, 2008; 34(10):1323–1326; doi: 10.1111/j.1524-4725.2008.34283.x
23.
KimW, ParkB, ParkS, et al.Antiwrinkle effect of adipose-derived stem cell: Activation of dermal fibroblast by secretory factors. J Dermatol Sci, 2009; 53(2):96–102; doi: 10.1016/j.jdermsci.2008.08.007
24.
KimW, ParkB, KimH, et al.Evidence supporting antioxidant action of adipose-derived stem cells: Protection of human dermal fibroblasts from oxidative stress. J Dermatol Sci, 2008; 49(2):133–142; doi: 10.1016/j.jdermsci.2007.08.004
25.
LeeE, XiaY, KimW, et al.Hypoxia-enhanced wound-healing function of adipose-derived stem cells: Increase in stem cell proliferation and up-regulation of VEGF and bFGF. Wound Repair Regen, 2009; 17(4):540–547; doi: 10.1111/j.1524-475X.2009.00499.x
26.
KimW, ParkB, SungJ. Protective role of adipose-derived stem cells and their soluble factors in photoaging. Arch Dermatol Res, 2009; 301(5):329–336; doi: 10.1007/s00403-009-0951-9
27.
KimW, ParkS, AhnS, et al.Whitening effect of adipose-derived stem cells: A critical role of TGF-beta 1. Biol Pharm Bull, 2008; 31(4):606–610; doi: 10.1248/bpb.31.606
28.
KimW, ParkB, SungJ, et al.Wound heating effect of adipose-derived stem cells: A critical role of secretory factors on human dermal fibroblasts. J Dermatol Sci, 2007; 48(1):15–24; doi: 10.1016/j.jdermsci.2007.05.018
29.
KimS, ImG, KimY, et al.Fortifying angiogenic efficacy of conditioned media using phototoxic-free blue light for wound healing. Bioeng Transl Med, 2022; 8(3):e10462; doi: 10.1002/btm2.10462
30.
KimY, LeeS, ImJ, et al.Increasing angiogenic efficacy of conditioned medium using light stimulation of human adipose-derived stem cells. Commun Biol, 2022; 5(1):957; doi: 10.1038/s42003-022-03838-3
31.
LeeS, KimY, KimY, et al.Enhancing therapeutic efficacy of human adipose-derived stem cells by modulating photoreceptor expression for advanced wound healing. Stem Cell Res Ther, 2022; 13(1):215; doi: 10.1186/s13287-022-02892-2.
32.
KimY, ImG, KimS, et al.Anti-senescence ion-delivering nanocarrier for recovering therapeutic properties of long-term-cultured human adipose-derived stem cells. J Nanobiotechnol, 2021; 19(1):352; doi: 10.1186/s12951-021-01098-7
33.
KimY, JungE, ImG, et al.Regulation of intracellular transition metal ion level with a pH-sensitive inorganic nanocluster to improve therapeutic angiogenesis by enriching conditioned medium retrieved from human adipose derived stem cells. Nano Convergence, 2020; 7(1):34; doi: 10.1186/s40580-020-00244-5
34.
LeeJ, ChaeS, YoonD, et al.Angiogenic factors secreted from human ASC spheroids entrapped in an alginate-based hierarchical structure via combined 3D printing/electrospinning system. Biofabrication, 2020; 12(4):045028; doi: 10.1088/1758-5090/abaf9a
35.
HurW, LeeH, MinH, et al.Regeneration of full-thickness skin defects by differentiated adipose-derived stem cells into fibroblast-like cells by fibroblast-conditioned medium. Stem Cell Res Ther, 2017; 8(1):92; doi: 10.1186/s13287-017-0520-7
36.
KwonS, BhangS, JangH, et al.Conditioned medium of adipose-derived stromal cell culture in three-dimensional bioreactors for enhanced wound healing. J Surg Res, 2015; 194(1):8–17; doi: 10.1016/j.jss.2014.10.053
37.
WonC, ParkG, WuX, et al.The basic mechanism of hair growth stimulation by adipose-derived stem cells and their secretory factors. Curr Stem Cell Res Ther, 2017; 12(7):535–543; doi: 10.2174/1574888X12666170829161058
38.
KimR, ParkS, LeeC, et al.Alternative new mesenchymal stem cell source exerts tumor tropism through ALCAM and N-cadherin via regulation of microRNA-192 and-218. Mol Cell Biochem, 2017; 427(1–2):177–185; doi: 10.1007/s11010-016-2909-5
39.
MeiS, QinS, TangR, et al.Lipopolysaccharide alters VEGF-A secretion of mesenchymal stem cells via the integrin beta 3-PI3K-AKT pathway. Mol Cell Toxicol [Epub ahead of print]; doi: 10.1007/s13273-022-00315-0
40.
LiuY, ZhangT, TanP, et al.Superiority of adipose-derived CD34+cells over adipose-derived stem cells in promoting ischemic tissue survival. Stem Cell Rev Rep, 2022; 18(2):660–671; doi: 10.1007/s12015-021-10276-x
41.
XinY, XuP, WangX, et al.Human foreskin-derived dermal stem/progenitor cell-conditioned medium combined with hyaluronic acid promotes extracellular matrix regeneration in diabetic wounds. Stem Cell Res Ther, 2021; 12(1):49; doi: 10.1186/s13287-020-02116-5
42.
ChenB, CaiJ, WeiY, et al.Exosomes are comparable to source adipose stem cells in fat graft retention with up-regulating early inflammation and angiogenesis. Plast Reconstr Surg, 2019; 144(5):816E–827E; doi: 10.1097/PRS.0000000000006175
43.
LiT, MaH, MaH, et al.Mussel-inspired nanostructures potentiate the immunomodulatory properties and angiogenesis of mesenchymal stem cells. ACS Appl Mater Interfaces, 2019; 11(19):17134–17146; doi: 10.1021/acsami.8b22017
44.
WangX, WangY, ZhouX, et al.Conditioned medium from adipose-derived stem cell inhibits Jurkat Cell Proliferation through TGF-beta 1 and p38/MAPK pathway. Anal Cell Pathol, 2019; 2019:2107414; doi: 10.1155/2019/2107414
45.
CaiY, LiJ, JiaC, et al.Therapeutic applications of adipose cell-free derivatives: A review. Stem Cell Res Ther, 2020; 11(1):312; doi: 10.1186/s13287-020-01831-3
46.
ChuY, WangY, PengW, et al.STAT3 activation by IL-6 from adipose-derived stem cells promotes endometrial carcinoma proliferation and metastasis. Biochem Biophys Res Commun, 2018; 500(3):626–631; doi: 10.1016/j.bbrc.2018.04.121
47.
WangT, YuX, LinJ, et al.Adipose-derived stem cells inhibited the proliferation of bladder tumor cells by S Phase Arrest and Wnt/beta-Catenin Pathway. Cell Reprogram, 2019; 21(6):331–338; doi: 10.1089/cell.2019.0047
48.
LeeT, LaiT, LinS, et al.Conditioned medium from adipose-derived stem cells attenuates ischemia/reperfusion-induced cardiac injury through the microRNA-221/222/PUMA/ETS-1 pathway. Theranostics, 2021; 11(7):3131–3149; doi: 10.7150/thno.52677
49.
LeeS, KimK, KimO, et al.Determination of optimized oxygen partial pressure to maximize the liver regenerative potential of the secretome obtained from adipose-derived stem cells. Stem Cell Res Ther, 2017; 8(1):181; doi: 10.1186/s13287-017-0635-x
50.
LaiJ, RoganH, KajiyamaG, et al.Interaction between osteoarthritic chondrocytes and adipose-derived stem cells is dependent on cell distribution in three-dimension and transforming growth factor-beta 3 induction. Tissue Eng A, 2015; 21(5–6):992–1002; doi: 10.1089/ten.tea.2014.0244
51.
GuoS, WangT, ZhangS, et al.Adipose-derived stem cell-conditioned medium protects fibroblasts at different senescent degrees from UVB irradiation damages. Mol Cell Biochem, 2020; 463(1–2):67–78; doi: 10.1007/s11010-019-03630-8
52.
RatushnyyA, EzdakovaM, YakubetsD, et al.Angiogenic activity of human adipose-derived mesenchymal stem cells under simulated microgravity. Stem Cells Dev, 2018; 27(12):831–837; doi: 10.1089/scd.2017.0262
53.
LeviB, NelsonE, LiS, et al.Dura mater stimulates human adipose-derived stromal cells to undergo bone formation in mouse calvarial defects. Stem Cells, 2011; 29(8):1241–1255; doi: 10.1002/stem.670
54.
CooperD, WangC, PatelR, et al.Human adipose-derived stem cell conditioned media and exosomes containing MALAT1 promote human dermal fibroblast migration and ischemic wound healing. Adv Wound Care, 2018; 7(9):299–308; doi: 10.1089/wound.2017.0775
55.
ChenL, ZhengQ, LiuY, et al.Adipose-derived stem cells promote diabetic wound healing via the recruitment and differentiation of endothelial progenitor cells into endothelial cells mediated by the VEGF-PLC gamma-ERK pathway. Arch Biochem Biophys, 2020; 692:108531; doi: 10.1016/j.abb.2020.108531
56.
CollawnS, MobleyJ, BanerjeeN, et al.Conditioned media from adipose-derived stromal cells accelerates healing in 3-dimensional skin cultures. Ann Plast Surg, 2016; 76(4):446–452; doi: 10.1097/SAP.0000000000000754
57.
GuoX, SchaudinnC, Blume-PeytaviU, et al.Effects of adipose-derived stem cells and their conditioned medium in a human ex vivo wound model. Cells, 2022; 11(7):1178; doi: 10.3390/cells11071198
58.
ChengJ, HsuC, HsuS, et al.Adipose-derived mesenchymal stem cells-conditioned medium modulates the expression of inflammation induced bone morphogenetic protein-2, -5 and -6 as well as compared with shockwave therapy on rat knee osteoarthritis. Biomedicines, 2021; 9(10):1399; doi: 10.3390/biomedicines9101399
59.
FilidouE, KandilogiannakisL, TarapatziG, et al.Conditioned medium from a human adipose-derived stem cell line ameliorates inflammation and fibrosis in a lung experimental model of idiopathic pulmonary fibrosis. Life Sci, 2021; 287:120123; doi: 10.1016/j.lfs.2021.120123
60.
DengZ, PoliakovA, HardyRW, et al.Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes, 2009; 58(11):2498–2505; doi: 10.2337/db09-0216
61.
ThomouT, MoriMA, DreyfussJM, et al.Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature, 2017; 542(7642):450–455; doi: 10.1038/nature21365
62.
CreweC, JoffinN, RutkowskiJM, et al.An endothelial-to-adipocyte extracellular vesicle axis governed by metabolic state. Cell, 2018; 175(3):695–708.e13; doi: 10.1016/j.cell.2018.09.005
63.
ZhangY, YuM, TianW. Physiological and pathological impact of exosomes of adipose tissue. Cell Prolif, 2016; 49(1):3–13; doi: 10.1111/cpr.12233.
64.
BaroneL, RossiF, ValdattaL, et al.Human adipose-derived stem cell-conditioned medium promotes vascularization of nanostructured scaffold transplanted into nude mice. Nanomaterials, 2022; 12(9):1521; doi: 10.3390/nano12091521
65.
ChenL, ChengL, WangZ, et al.Conditioned medium-electrospun fiber biomaterials for skin regeneration. Bioactive Mater, 2021; 6(2):361–374; doi: 10.1016/j.bioactmat.2020.08.022
66.
KoivunotkoE, SnirviJ, MerivaaraA, et al.Angiogenic potential of human adipose-derived mesenchymal stromal cells in nanofibrillated cellulose hydrogel. Biomedicines, 2022; 10(10):2584; doi: 10.3390/biomedicines10102584
67.
LiS, SunJ, YangJ, et al.Gelatin methacryloyl (GelMA) loaded with concentrated hypoxic pretreated adipose-derived mesenchymal stem cells (ADSCs) conditioned medium promotes wound healing and vascular regeneration in aged skin. Biomater Res, 2023; 27(1):11; doi: 10.1186/s40824-023-00352-3
68.
XiaoS, DengY, MoX, et al.Promotion of hair growth by conditioned medium from extracellular matrix/stromal vascular fraction gel in C57BL/6 mice. Stem Cells Int, 2020; 2020:9054514; doi: 10.1155/2020/9054514
69.
NaritaK, FukuokaH, SekiyamaT, et al.Sequential scalp assessment in hair regeneration therapy using an adipose-derived stem cell-conditioned medium. Dermatol Surg, 2020; 46(6):819–825; doi: 10.1097/DSS.0000000000002128
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