References

Sun H, Saeedi P, Karuranga S IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022; 183 https://doi.org/10.1016/j.diabres.2021.109119

Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005; 293:(2)217-228 https://doi.org/10.1001/jama.293.2.217

Martin P. Wound healing--aiming for perfect skin regeneration. Science. 1997; 276:(5309)75-81 https://doi.org/10.1126/science.276.5309.75

Tsourdi E, Barthel A, Rietzsch H Current aspects in the pathophysiology and treatment of chronic wounds in diabetes mellitus. BioMed Res Int. 2013; 2013:1-6 https://doi.org/10.1155/2013/385641

Mirabzadeh A, Ladani MJ, Imani B Maggot therapy for wound care in Iran: a case series of the first 28 patients. J Wound Care. 2017; 26:(3)137-143 https://doi.org/10.12968/jowc.2017.26.3.137

Cramer JA. A systematic review of adherence with medications for diabetes. Diabetes Care. 2004; 27:(5)1218-1224 https://doi.org/10.2337/diacare.27.5.1218

Goldsmith EC, Bradshaw AD, Zile MR, Spinale FG. Myocardial fibroblast–matrix interactions and potential therapeutic targets. J Mol Cell Cardiol. 2014; 70:92-99 https://doi.org/10.1016/j.yjmcc.2014.01.008

Sriram G, Bigliardi PL, Bigliardi-Qi M. Fibroblast heterogeneity and its implications for engineering organotypic skin models in vitro. Eur J Cell Biol. 2015; 94:(11)483-512 https://doi.org/10.1016/j.ejcb.2015.08.001

Warsinske HC, Ashley SL, Linderman JJ Identifying Mechanisms of Homeostatic Signaling in Fibroblast Differentiation. Bull Math Biol. 2015; 77:(8)1556-1582 https://doi.org/10.1007/s11538-015-0096-2

Hsieh JY, Wang HW, Chang SJ Mesenchymal stem cells from human umbilical cord express preferentially secreted factors related to neuroprotection, neurogenesis, and angiogenesis. PLoS One. 2013; 8:(8) https://doi.org/10.1371/journal.pone.0072604

Kasap Ş, Barutçu A, Güç H Effects of keratinocytes differentiated from embryonic and adipogenic stem cells on wound healing in a diabetic mouse model. Wounds. 2017; 29:(11)297-305

Gomathysankar S, Halim AS, Yaacob NS. Proliferation of keratinocytes induced by adipose-derived stem cells on a chitosan scaffold and its role in wound healing, a review. Arch Plast Surg. 2014; 41:(5)452-457 https://doi.org/10.5999/aps.2014.41.5.452

Carson CT, Aigner S, Gage FH. Stem cells: the good, bad and barely in control. Nat Med. 2006; 12:(11)1237-1238 https://doi.org/10.1038/nm1106-1237

Park SR, Kim JW, Jun HS Stem cell secretome and its effect on cellular mechanisms relevant to wound healing. Mol Ther. 2018; 26:(2)606-617 https://doi.org/10.1016/j.ymthe.2017.09.023

Jiang Z, Liu G, Meng F Paracrine effects of mesenchymal stem cells on the activation of keratocytes. Br J Ophthalmol. 2017; 101:(11)1583-1590 https://doi.org/10.1136/bjophthalmol-2016-310012

Aarabi S, Longaker MT, Gurtner GC. Hypertrophic scar formation following burns and trauma: new approaches to treatment. PLoS Med. 2007; 4:(9) https://doi.org/10.1371/journal.pmed.0040234

Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med. 1999; 341:(10)738-746 https://doi.org/10.1056/NEJM199909023411006

Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008; 453:(7193)314-321 https://doi.org/10.1038/nature07039

Tomasek JJ, Gabbiani G, Hinz B Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol. 2002; 3:(5)349-363 https://doi.org/10.1038/nrm809

Lee PY, Cobain E, Huard J, Huang L. Thermosensitive hydrogel PEG-PLGA-PEG enhances engraftment of muscle-derived stem cells and promotes healing in diabetic wound. Mol Ther. 2007; 15:(6)1189-1194 https://doi.org/10.1038/sj.mt.6300156

Ko SH, Nauta A, Wong V The role of stem cells in cutaneous wound healing: what do we really know?. Plast Reconstr Surg. 2011; 127:10S-20S https://doi.org/10.1097/PRS.0b013e3181fbe2d8

Kirby GT, Mills SJ, Cowin AJ, Smith LE. Stem cells for cutaneous wound healing. BioMed Res Int. 2015; 2015:1-11 https://doi.org/10.1155/2015/285869

Peng C, Chen B, Kao HK Lack of FGF-7 further delays cutaneous wound healing in diabetic mice. Plast Reconstr Surg. 2011; 128:(6)673e-684e https://doi.org/10.1097/PRS.0b013e318230c521

Ho CH, Lan CW, Liao CY Mesenchymal stem cells and their conditioned medium can enhance the repair of uterine defects in a rat model. J Chin Med Assoc. 2018; 81:(3)268-276 https://doi.org/10.1016/j.jcma.2017.03.013

Gonchar IV, Lipunov AR, Afanasov IM Platelet rich plasma and growth factors cocktails for diabetic foot ulcers treatment: state of art developments and future prospects. Diabetes Metab Syndr. 2018; 12:(2)189-194 https://doi.org/10.1016/j.dsx.2017.09.007

Kim WS, Park BS, Sung JH Wound healing effect of adipose-derived stem cells: a critical role of secretory factors on human dermal fibroblasts. J Dermatol Sci. 2007; 48:(1)15-24 https://doi.org/10.1016/j.jdermsci.2007.05.018

Kober J, Gugerell A, Schmid M Wound Healing Effect of Conditioned Media Obtained From Adipose Tissue on Human Skin Cells: A Comparative in Vitro Study. Ann Plast Surg. 2016; 77:(2)156-163 https://doi.org/10.1097/sap.0000000000000358

Yuan B, Broadbent JA, Huan J, Yang H. The Effects of Adipose Stem Cell-Conditioned Media on Fibrogenesis of Dermal Fibroblasts Stimulated by Transforming Growth Factor-β1. J Burn Care Res. 2018; 39:(1)129-140 https://doi.org/10.1097/bcr.0000000000000558

Komi DEA, Khomtchouk K, Santa Maria PL. A Review of the Contribution of Mast Cells in Wound Healing: Involved Molecular and Cellular Mechanisms. Clin Rev Allergy Immunol. 2020; 58:(3)298-312 https://doi.org/10.1007/s12016-019-08729-w

DiPietro LA. Angiogenesis and wound repair: when enough is enough. J Leukoc Biol. 2016; 100:(5)979-984 https://doi.org/10.1189/jlb.4MR0316-102R

Korntner S, Lehner C, Gehwolf R Limiting angiogenesis to modulate scar formation. Adv Drug Deliv Rev. 2019; 170-189 https://doi.org/10.1016/j.addr.2018.02.010

Danisovic L, Oravcova L, Krajciova L Effect of long-term culture on the biological and morphological characteristics of human adipose tissue-derived stem cells. J Physiol Pharmacol. 2017; 68:149-158

Oravcova L, Bohac M, Krajciova L Effect of serial passaging on the morphology and biological characteristics of human adipose tissue-derived stem cells. Online J Biol Sci. 2016; 16:(4)145-151 https://doi.org/10.3844/ojbsci.2016.145.151

Animal studies

Paracrine effects of adipose-derived stem cells in cutaneous wound healing in streptozotocin-induced diabetic rats

01 March 2022

Research

Abstract

Objective:

The purpose of this study was to explore the paracrine effects of adipose-derived stem cells (ASCs) on cutaneous wound healing in diabetic rats

Method:

The ASCs were isolated and identified by immunofluorescent staining. The ASCs-conditioned medium (ASCs-CM) was harvested. Cell counting kit (CCK)-8 assay, scratch experiments, western blot and quantitative polymerase chain reaction (qPCR) were performed to observe the effects of ASCs-CM on fibroblasts. A full-thickness skin wound diabetic rat model was prepared, using 34 male, Sprague Dawley rats. ASCs-CM or negative-control medium (N-CM) was injected around the wound surface. The existing wound area was measured on days 4, 8, 12 and 16 after the postoperative day, and the wound tissues were collected for immunohistochemical staining and qPCR quantitative study.

Results:

In this experiment, the isolated cells were characterised as ASCs. The results of CCK-8 assay, cell scratch test, western blot and qPCR showed ASCs-CM could significantly promote the proliferation, migration and differentiation of fibroblasts. Simultaneously, the healing rate of full-thickness skin wounds in diabetic rats was significantly higher in the ASCs-CM group than the N-CM group on days 4, 8, 12 and 16. Immunohistochemical staining and qPCR results showed that the expression of vascular endothelial growth factor (VEGF, days 4 and 8), α-smooth muscle actin (SMA) (days 4 and 16), transforming growth factor (TGF)-β1 (days 4, 8 and 12) were higher in the ASCs-CM group than that of the N-CM group (p<0.05).

Conclusion:

This experiment demonstrated that ASCs-CM may accelerate wound healing in diabetic rats by promoting the secretion of TGF-β1, VEGF and the proliferation, migration and differentiation of fibroblasts.

According to the International Diabetes Federation Diabetes Atlas of 2021, the number of adult patients with diabetes worldwide has reached 536.6 million.¹ Diabetic foot ulcers (DFUs) are estimated to occur in 25% of all patients with diabetes, resulting in extensive emotional, functional and economic consequences for patients and an added burden on the healthcare system.²

The high glucose state caused by diabetes can impair wound healing, and the incidence rate of diabetic ulcers is >25%.³ The standard treatment of diabetic ulcers focuses on blood glucose control, offloading high pressure, surgical debridement of necrotic tissue, as well as antibiotic therapy for bacterial superinfection.^4,5 However, in some cases, hard-to-heal diabetic ulcers are not responsive to these treatments and many patients with diabetic ulcers fail to adhere with these supportive and medical therapies.⁶

Register now to continue reading

Thank you for visiting Journal of Wound Care's World Union of Wound Healing Supplement and reading some of our peer-reviewed resources for healthcare professionals. To read more, please register today.

Or continue by

Signing in with your registered email address

adipose-derived stem cells

animal model

conditioned medium

diabetes

fibroblasts

wound

wound care

wound healing