Top

Published in:

01-01-2024 | ORIGINAL PAPER

Alternative viewpoint against diabetic wound based on stem cell secretome that can mediated angiogenesis and reduce inflammation

Authors: Rezvan Izadi, Seyed Hesamaldin Hejazi, Seifollah Bahramikia

Published in: Archives of Dermatological Research | Issue 1/2024

Abstract

Diabetes mellitus, as an important metabolic disorder, affects the health of millions of people worldwide. A diabetic wound is one of the complications of diabetes. The stem cell secretome can particularly affect the wound healing process in diabetic wounds. The present study aimed to investigate the effects of Adipose-derived stem cells (ASCs) secretome on the skin wound healing process, angiogenesis, and inflammation in diabetic rats. For this purpose, ASCs were extracted from Adipose tissue and confirmed by flow cytometry and cell differentiation. Secretome was prepared. 27 rats were divided into three groups, non-diabetic, diabetic (treated with phosphate-buffered saline), and diabetics treated with secretome. The levels of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) were examined by the enzyme-linked immunosorbent assay (ELISA) was performed in the skin tissues of all groups. Hematoxylin and eosin (H&E) staining was performed. The level of VEGF was higher in the diabetic group treated with secretome as compared to the other two groups, while the level of TGF-β was lower in this group, compared to the diabetic group. Based on the results of H&E staining, the epidermal thickness and angiogenesis were higher in the diabetic group treated with secretome, whereas edema, number of inflammatory cells, and epidermal damage were lower in this group, compared to the diabetic group. Subcutaneous injection of secretome can lead to diabetic wound healing by increasing growth factors associated with angiogenesis such as VEGF, increasing angiogenesis, regulating TGF-β levels, reducing inflammatory cells.

Bai Q, Han K, Dong K et al (2020) Potential applications of nanomaterials and technology for diabetic wound healing. Int J Nanomed 15:9717–9743CrossRef

An R, Zhang Y, Qiao Y et al (2020) Adipose stem cells isolated from diabetic mice improve cutaneous wound healing in streptozotocin-induced diabetic mice. Stem Cell Res Ther. https://doi.org/10.1186/s13287-020-01621-xCrossRefPubMedPubMedCentral

Hamada M, Iwata T, Kato Y et al (2017) Xenogeneic transplantation of human adipose-derived stem cell sheets accelerate angiogenesis and the healing of skin wounds in a Zucker Diabetic Fatty rat model of obese diabetes. Regen Ther 6:65–73. https://doi.org/10.1016/j.reth.2017.02.002CrossRefPubMedPubMedCentral

O’Loughlin A, Kulkarni M, Creane M et al (2013) Topical administration of allogeneic mesenchymal stromal cells seeded in a collagen scaffold augments wound healing and increases angiogenesis in the diabetic rabbit ulcer. Diabetes 62:2588–2594. https://doi.org/10.2337/db12-1822CrossRefPubMedPubMedCentral

Chen S, Shi J, Zhang M et al (2015) Mesenchymal stem cell-laden anti-inflammatory hydrogel enhances diabetic wound healing. Sci Rep 5:18104. https://doi.org/10.1038/srep18104CrossRefPubMedCentral

Xu J, Zgheib C, Hodges MM et al (2017) Mesenchymal stem cells correct impaired diabetic wound healing by decreasing ECM proteolysis. Physiol Genom 49:541–548. https://doi.org/10.1152/physiolgenomics.00090.2016CrossRef

Kanji S, Das H (2017) Advances of stem cell therapeutics in cutaneous wound healing and regeneration. Mediators Inflamm. https://doi.org/10.1155/2017/5217967CrossRefPubMedPubMedCentral

Trzyna A, Banaś-Ząbczyk A (2021) Adipose-derived stem cells secretome and its potential application in “stem cell-free therapy.” Biomolecules 11:878CrossRefPubMedCentral

Guo X, Schaudinn C, Blume-Peytavi U et al (2022) Effects of adipose-derived stem cells and their conditioned medium in a human ex vivo wound model. Cells 11:1198. https://doi.org/10.3390/cells11071198CrossRefPubMedPubMedCentral

10.

An Y-H, Kim DH, Lee EJ et al (2021) High-efficient production of adipose-derived stem cell (ADSC) secretome through maturation process and its non-scarring wound healing applications. Front Bioeng Biotechnol. https://doi.org/10.3389/fbioe.2021.681501CrossRefPubMedPubMedCentral

11.

Bari E, Perteghella S, Di Silvestre D et al (2018) Pilot production of mesenchymal stem/stromal freeze-dried secretome for cell-free regenerative nanomedicine: a validated GMP-compliant process. Cells 7:190. https://doi.org/10.3390/cells7110190CrossRefPubMedPubMedCentral

12.

Foo JB, Looi QH, Chong PP et al (2021) Comparing the therapeutic potential of stem cells and their secretory products in regenerative medicine. Stem Cells Int 2021:1–30. https://doi.org/10.1155/2021/2616807CrossRef

13.

Sumarwoto T, Suroto H, Mahyudin F et al (2021) Role of adipose mesenchymal stem cells and secretome in peripheral nerve regeneration. Ann Med Surg. https://doi.org/10.1016/j.amsu.2021.102482CrossRef

14.

Zhou X, Ning K, Ling B et al (2019) Multiple injections of autologous adipose-derived stem cells accelerate the burn wound healing process and promote blood vessel regeneration in a rat model. Stem Cells Dev 28:1463–1472. https://doi.org/10.1089/scd.2019.0113CrossRefPubMed

15.

Kato Y, Iwata T, Washio K et al (2017) Creation and transplantation of an adipose-derived stem cell (ASC) sheet in a diabetic wound-healing model. J Vis Exp. https://doi.org/10.3791/54539CrossRefPubMedPubMedCentral

16.

Azam M, Ghufran H, Butt H et al (2021) Curcumin preconditioning enhances the efficacy of adipose-derived mesenchymal stem cells to accelerate healing of burn wounds. Burns Trauma. https://doi.org/10.1093/burnst/tkab021CrossRefPubMedPubMedCentral

17.

Liu J, Qiu X, Lv Y et al (2020) Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages. Stem Cell Res Ther 11:507. https://doi.org/10.1186/s13287-020-02014-wCrossRefPubMedPubMedCentral

18.

Enderami SE, Soleimani M, Mortazavi Y et al (2018) Generation of insulin-producing cells from human adipose-derived mesenchymal stem cells on PVA scaffold by optimized differentiation protocol. J Cell Physiol 233:4327–4337. https://doi.org/10.1002/jcp.26266CrossRefPubMed

19.

Park S-R, Kim J-W, Jun H-S et al (2018) Stem cell secretome and its effect on cellular mechanisms relevant to wound healing. Mol Ther 26:606–617. https://doi.org/10.1016/j.ymthe.2017.09.023CrossRefPubMed

20.

Zhang S, Chen L, Zhang G, Zhang B (2020) Umbilical cord-matrix stem cells induce the functional restoration of vascular endothelial cells and enhance skin wound healing in diabetic mice via the polarized macrophages. Stem Cell Res Ther 11:39. https://doi.org/10.1186/s13287-020-1561-xCrossRefPubMedPubMedCentral

21.

Bai H, Kyu-Cheol N, Wang Z et al (2020) Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers. J Tissue Eng 11:204173142094724. https://doi.org/10.1177/2041731420947242CrossRef

22.

Kiritsi D, Nyström A (2018) The role of TGFβ in wound healing pathologies. Mech Ageing Dev 172:51–58. https://doi.org/10.1016/j.mad.2017.11.004CrossRefPubMed

23.

Wang J, Wu H, Peng Y et al (2021) Hypoxia adipose stem cell-derived exosomes promote high-quality healing of diabetic wound involves activation of PI3K/Akt pathways. J Nanobiotechnol. https://doi.org/10.1186/s12951-021-00942-0CrossRef

24.

Shin S, Lee J, Kwon Y et al (2021) Comparative proteomic analysis of the mesenchymal stem cells secretome from adipose, bone marrow, placenta and Wharton’s Jelly. Int J Mol Sci. https://doi.org/10.3390/ijms22020845CrossRefPubMedPubMedCentral

25.

Hu L, Hu J, Zhao J et al (2013) Side-by-side comparison of the biological characteristics of human umbilical cord and adipose tissue-derived mesenchymal stem cells. Biomed Res Int. https://doi.org/10.1155/2013/438243CrossRefPubMedPubMedCentral

26.

Zhang J, Liu Y, Chen Y et al (2020) Adipose-derived stem cells: current applications and future directions in the regeneration of multiple tissues. Stem Cells Int 2020:8810813. https://doi.org/10.1155/2020/8810813CrossRefPubMedPubMedCentral

27.

Moriyama M, Sahara S, Zaiki K et al (2019) Adipose-derived stromal/stem cells improve epidermal homeostasis. Sci Rep 9:18371. https://doi.org/10.1038/s41598-019-54797-5CrossRefPubMedPubMedCentral

28.

Jośko J, Gwóźdź B, Jedrzejowska-Szypułka H, Hendryk S (2000) Vascular endothelial growth factor (VEGF) and its effect on angiogenesis. Med Sci Monit 6:1047–1052PubMed

29.

Hu Y, Tao R, Chen L et al (2021) Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis. J Nanobiotechnol 19:150. https://doi.org/10.1186/s12951-021-00894-5CrossRef

30.

Galiano RD, Tepper OM, Pelo CR et al (2004) Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol 164:1935–1947. https://doi.org/10.1016/S0002-9440(10)63754-6CrossRefPubMedPubMedCentral

31.

Gonzalo-Gil E, Galindo-Izquierdo M (2014) Papel del factor de crecimiento transformador-beta (TGF-β) en la fisiopatología de la artritis reumatoide. Reumatol Clin 10:174–179. https://doi.org/10.1016/j.reuma.2014.01.009CrossRefPubMed

32.

Liarte S, Bernabé-García Á, Nicolás FJ (2020) Role of TGF-β in skin chronic wounds: a keratinocyte perspective. Cells 9:306CrossRefPubMedPubMedCentral

33.

de Mayo T, Conget P, Becerra-Bayona S et al (2017) The role of bone marrow mesenchymal stromal cell derivatives in skin wound healing in diabetic mice. PLoS One 12:e0177533. https://doi.org/10.1371/journal.pone.0177533CrossRefPubMedPubMedCentral

34.

Khayambashi P, Iyer J, Pillai S et al (2021) Hydrogel encapsulation of mesenchymal stem cells and their derived exosomes for tissue engineering. Int J Mol Sci. https://doi.org/10.3390/ijms22020684CrossRefPubMedPubMedCentral

35.

Cases-Perera O, Blanco-Elices C, Chato-Astrain J et al (2022) Development of secretome-based strategies to improve cell culture protocols in tissue engineering. Sci Rep 12:10003. https://doi.org/10.1038/s41598-022-14115-yCrossRefPubMedPubMedCentral

36.

McDonald TA, Zepeda ML, Tomlinson MJ et al (2010) Subcutaneous administration of biotherapeutics: current experience in animal models. Curr Opin Mol Ther 12:461–470PubMed

37.

Zeng Q-L, Liu D-W (2021) Mesenchymal stem cell-derived exosomes: An emerging therapeutic strategy for normal and chronic wound healing. World J Clin Cases 9:6218–6233. https://doi.org/10.12998/wjcc.v9.i22.6218CrossRefPubMedPubMedCentral

Title: Alternative viewpoint against diabetic wound based on stem cell secretome that can mediated angiogenesis and reduce inflammation
Authors: Rezvan Izadi
Seyed Hesamaldin Hejazi
Seifollah Bahramikia
Publication date: 01-01-2024
Publisher: Springer Berlin Heidelberg
Published in: Archives of Dermatological Research / Issue 1/2024
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI: https://doi.org/10.1007/s00403-023-02739-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Alternative viewpoint against diabetic wound based on stem cell secretome that can mediated angiogenesis and reduce inflammation

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2024

Teledermatology patient perspectives and preferences regarding acne scar treatment

Trichoscopic pearl: dynamic trichoscopy sequence of scalp psoriasis before and after the development of Auspitz’s sign

Shenghong liquid combined with nanosilver accelerates healing of foot ulcers in diabetic rats by inhibiting inflammation and increasing angiogenesis

Gender distribution and NIH funding rank in dermatology leadership: a cross-sectional analysis

Exploring dermatologists’ perspectives on vaccines in dermatology: a qualitative study

The burning truth about light therapy: a retrospective analysis of the MAUDE database on UV phototherapy and photodynamic therapy complications 2013–2023