The Application of Decellularized Adipose Tissue Promotes Wound Healing

Abstract

Background:

Due to adipose-derived stem cells (ASCs) being easy to obtain, their rapid proliferation rate, and their multidirectional differentiation capabilities, they have been widely used in the field of regenerative medicine. With the progress of decellularized adipose tissue (DAT) and adipose tissue engineering research, the role of DAT in promoting angiogenesis has gradually been emphasized.

Methods:

We examined the biological characteristics and biosafety of DAT and evaluated the stem cell maintenance ability and promotion of growth factor secretion through conducting in vitro and in vivo studies.

Results

The tested ASCs showed high rat:es of proliferation and adhered well to DAT. The expression levels of essential genes for cell stem maintenance, including OCT4, SOX2, and Nanog were low at 2–24 h and much higher at 48 and 96 h. The Adipogenic expression level of markers for ASCs proliferation including PPARγ, C/EPBα, and LPL increased from 2 to 96 h. Co-culture of ASCs and DAT increased the secretion of local growth factors, such as VEGF, PDGF-bb, bFGF, HGF, EGF, and FDGF-bb, and secretion gradually increased from 0 to 48 h. A model of full-thickness skin defects on the back of nude mice was established, and the co-culture of ASCs and DAT showed the best in vivo treatment effect.

Conclusion:

The application of DAT promotes wound healing, and DAT combined with ASCs may be a promising material in adipose tissue engineering and regenerative medicine.

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References

  1. 1.

    Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17:763–71.

    Article  PubMed Central  Google Scholar 

  2. 2.

    Shabbir A, Cox A, Rodriguez-Menocal L, Salgado M, Van Badiavas E. Mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro. Stem Cells Dev. 2015;24:1635–47.

    CAS  Article  PubMed Central  Google Scholar 

  3. 3.

    Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13:4279–95.

    CAS  Article  PubMed Central  Google Scholar 

  4. 4.

    Zuk PA. The adipose-derived stem cell: looking back and looking ahead. Mol Biol Cell. 2010;21:1783–7.

    CAS  Article  PubMed Central  Google Scholar 

  5. 5.

    Cheng H, Kimura K, Peter AK, Cui L, Ouyang K, Shen T, et al. Loss of enigma homolog protein results in dilated cardiomyopathy. Circ Res. 2010;107:348–56.

    CAS  Article  PubMed Central  Google Scholar 

  6. 6.

    Armentano I, Fortunati E, Mattioli S, Rescignano N, Kenny JM. Biodegradable composite scaffolds: a strategy to modulate stem cell behaviour. Recent Pat Drug Deliv Formul. 2013;7:9–17.

    CAS  Article  PubMed Central  Google Scholar 

  7. 7.

    Furth ME, Atala A, Van Dyke ME. Smart biomaterials design for tissue engineering and regenerative medicine. Biomaterials. 2007;28:5068–73.

    CAS  Article  PubMed Central  Google Scholar 

  8. 8.

    Irminger-Finger I, Kargul J, Laurent GJ. Extra cellular matrix a modular soil for stem cells. Int J Biochem Cell Biol. 2016;81:164.

    CAS  Article  PubMed Central  Google Scholar 

  9. 9.

    Omidi E, Fuetterer L, Reza Mousavi S, Armstrong RC, Flynn LE, Samani A. Characterization and assessment of hyperelastic and elastic properties of decellularized human adipose tissues. J Biomech. 2014;47:3657–63.

    Article  PubMed Central  Google Scholar 

  10. 10.

    Zhang Q, Johnson JA, Dunne LW, Chen Y, Iyyanki T, Wu Y, et al. Decellularized skin/adipose tissue flap matrix for engineering vascularized composite soft tissue flaps. Acta Biomater. 2016;35:166–84.

    CAS  Article  PubMed Central  Google Scholar 

  11. 11.

    Yang G, Rothrauff BB, Lin H, Yu S, Tuan RS. Tendon-derived extracellular matrix enhances transforming growth factor-β3-induced tenogenic differentiation of human adipose-derived stem cells. Tissue Eng Part A. 2017;23:166–76.

    CAS  Article  PubMed Central  Google Scholar 

  12. 12.

    Adam Young D, Bajaj V, Christman KL. Award winner for outstanding research in the PhD category, 2014 society for biomaterials annual meeting and exposition, denver, colorado, April 16–19, 2014: decellularized adipose matrix hydrogels stimulate in vivo neovascularization and adipose formation. J Biomed Mater Res Part A. 2014;102:1641–51.

    CAS  Article  Google Scholar 

  13. 13.

    Ting AC, Craft RO, Palmer JA, Gerrand YW, Penington AJ, Morrison WA, et al. The adipogenic potential of various extracellular matrices under the influence of an angiogenic growth factor combination in a mouse tissue engineering chamber. Acta Biomater. 2014;10:1907–18.

    CAS  Article  Google Scholar 

  14. 14.

    Han TT, Toutounji S, Amsden BG, Flynn LE. Adipose-derived stromal cells mediate in vivo adipogenesis, angiogenesis and inflammation in decellularized adipose tissue bioscaffolds. Biomaterials. 2015;72:125–37.

    CAS  Article  Google Scholar 

  15. 15.

    Zeng Y, Zhu L, Han Q, Liu W, Mao X, Li Y, et al. Preformed gelatin microcryogels as injectable cell carriers for enhanced skin wound healing. Acta Biomater. 2015;25:291–303.

    CAS  Article  Google Scholar 

  16. 16.

    Dong Y, Cui M, Qu J, Wang X, Kwon SH, Barrera J, et al. Conformable hyaluronic acid hydrogel delivers adipose-derived stem cells and promotes regeneration of burn injury. Acta Biomater. 2020;108:56–66.

    CAS  Article  Google Scholar 

  17. 17.

    Yamamoto D, Tada K, Suganuma S, Hayashi K, Nakajima T, Nakada M, et al. Differentiated adipose-derived stem cells promote peripheral nerve regeneration. Muscle Nerve. 2020;62:119–27.

    CAS  Article  PubMed Central  Google Scholar 

  18. 18.

    Shafaei H, Kalarestaghi H. Adipose-derived stem cells: An appropriate selection for osteogenic differentiation. J Cell Physiol. 2020. https://doi.org/10.1002/jcp.29681.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Heo JS, Choi Y, Kim HS, Kim HO. Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue. Int J Mol Med. 2016;37:115–25.

    Article  PubMed Central  Google Scholar 

  20. 20.

    Huang SJ, Fu RH, Shyu WC, Liu SP, Jong GP, Chiu YW, et al. Adipose-derived stem cells: isolation, characterization, and differentiation potential. Cell Transplant. 2013;22:701–9.

    Article  PubMed Central  Google Scholar 

  21. 21.

    Morissette Martin P, Shridhar A, Yu C, Brown C, Flynn LE. Decellularized adipose tissue scaffolds for soft tissue regeneration and adipose-derived stem/stromal cell delivery. In: Bunnell BA, Gimble JM, editors. Adipose-derived stem cells: methods and protocols. New York: Springer New York; 2018. p. 53–71.

    Google Scholar 

  22. 22.

    Mohiuddin OA, Campbell B, Poche JN, Thomas-Porch C, Hayes DA, Bunnell BA, et al. Decellularized adipose tissue: biochemical composition, in vivo analysis and potential clinical applications. In: Turksen K, editor. Cell biology and translational medicine, volume 6: stem cells: their heterogeneity, niche and regenerative potential. Cham: Springer; 2020. p. 57–70.

    Google Scholar 

  23. 23.

    Choi YC, Choi JS, Kim BS, Kim JD, Yoon HI, Cho YW. Decellularized extracellular matrix derived from porcine adipose tissue as a xenogeneic biomaterial for tissue engineering. Tissue Eng Part C Methods. 2012;18:866–76.

    CAS  Article  PubMed Central  Google Scholar 

  24. 24.

    Yu C, Kornmuller A, Brown C, Hoare T, Flynn LE. Decellularized adipose tissue microcarriers as a dynamic culture platform for human adipose-derived stem/stromal cell expansion. Biomaterials. 2017;120:66–80.

    CAS  Article  PubMed Central  Google Scholar 

  25. 25.

    Zhao Y, Fan J, Bai S. Biocompatibility of injectable hydrogel from decellularized human adipose tissue in vitro and in vivo. J Biomed Mater Res B Appl Biomater. 2019;107:1684–94.

    CAS  Article  PubMed Central  Google Scholar 

  26. 26.

    Mohiuddin OA, Campbell B, Poche JN, Ma M, Rogers E, Gaupp D, et al. Decellularized adipose tissue hydrogel promotes bone regeneration in critical-sized mouse femoral defect model. Front Bioeng Biotechnol. 2019;7:211.

    Article  PubMed Central  Google Scholar 

  27. 27.

    Dong J, Yu M, Zhang Y, Yin Y, Tian W. Recent developments and clinical potential on decellularized adipose tissue. J Biomed Mater Res A. 2018;106:2563–74.

    CAS  Article  PubMed Central  Google Scholar 

  28. 28.

    Zhang S, Lu Q, Cao T, Toh WS. Adipose tissue and extracellular matrix development by injectable decellularized adipose matrix loaded with basic fibroblast growth factor. Plast Reconstr Surg. 2016;137:1171–80.

    CAS  Article  PubMed Central  Google Scholar 

  29. 29.

    Yu C, Bianco J, Brown C, Fuetterer L, Watkins JF, Samani A, et al. Porous decellularized adipose tissue foams for soft tissue regeneration. Biomaterials. 2013;34:3290–302.

    CAS  Article  PubMed Central  Google Scholar 

  30. 30.

    Turner AE, Yu C, Bianco J, Watkins JF, Flynn LE. The performance of decellularized adipose tissue microcarriers as an inductive substrate for human adipose-derived stem cells. Biomaterials. 2012;33:4490–9.

    CAS  Article  Google Scholar 

  31. 31.

    Thomas-Porch C, Li J, Zanata F, Martin EC, Pashos N, Genemaras K, et al. Comparative proteomic analyses of human adipose extracellular matrices decellularized using alternative procedures. J Biomed Mater Res A. 2018;106:2481–93.

    CAS  Article  PubMed Central  Google Scholar 

  32. 32.

    Porzionato A, Stocco E, Barbon S, Grandi F, Macchi V, De Caro R. Tissue-engineered grafts from human decellularized extracellular matrices: a systematic review and future perspectives. Int J Mol Sci. 2018;19:4117.

    Article  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the Natural Science Foundation of China (No. 81601694).

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Correspondence to Lin Zhu or Zhifei Liu.

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All animal care and experiments were performed in accordance with the guidelines of Institutional Animal Care and Use Committee of Chinese Academy of Medical Sciences.

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Lin Zhu and Zhifei Liu share the corresponding relationship equally.

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Cite this article

Xia, Z., Guo, X., Yu, N. et al. The Application of Decellularized Adipose Tissue Promotes Wound Healing. Tissue Eng Regen Med (2020). https://doi.org/10.1007/s13770-020-00286-0

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Keywords

  • Decellularized adipose tissue
  • Adipose-derived stem cells
  • Nude mouse model
  • Wound healing