Limited Efficacy of Adipose Stromal Cell Secretome-Loaded Skin-Derived Hydrogels to Augment Skin Flap Regeneration in Rats

Imagem de Miniatura
Arquivos
art_VRIEND_Limited_Efficacy_of_Adipose_Stromal_Cell_SecretomeLoaded_SkinDerived_2022.PDF (1.12 MB)
Citações na Scopus
6
Tipo de produção
article
Data de publicação
2022
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
MARY ANN LIEBERT, INC
Autores
VRIEND, Linda
DONGEN, Joris A. van
BROUWER, Linda A.
BUIKEMA, Henk J.
BONGIOVANNI, Laura
BRUIN, Alain de
LEI, Berend van der
Citação
STEM CELLS AND DEVELOPMENT, v.31, n.19-20, p.630-640, 2022
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Insufficient vascularization is a recurring cause of impaired pedicled skin flap healing. The administration of adipose tissue-derived stromal cells' (ASCs') secretome is a novel approach to augment vascularization. Yet, the secretome comprised of soluble factors that require a sustained-release vehicle to increase residence time. We hypothesized that administration of a hydrogel derived from decellularized extracellular matrix (ECM) of porcine skin with bound trophic factors from ASCs enhances skin flap viability and wound repair in a rat model. Porcine skin was decellularized and pepsin-digested to form a hydrogel at 37 degrees C. Conditioned medium (CMe) of human ASC was collected, concentrated 20-fold, and mixed with the hydrogel. Sixty Wistar rats were included. A dorsal skin flap (caudal based) of 3 x 10 cm was elevated for topical application of DMEM (group I), a prehydrogel with or without ASC CMe (groups II and III), or ASC CMe (group IV). After 7, 14, and 28 days, perfusion was measured, and skin flaps were harvested for wound healing assessment and immunohistochemical analysis. Decellularized skin ECM hydrogel contained negligible amounts of DNA (11.6 +/- 0.6 ng/mg), was noncytotoxic and well tolerated by rats. Irrespective of ASC secretome, ECM hydrogel application resulted macroscopically and microscopically in similar dermal wound healing in terms of proliferation, immune response, and matrix remodeling as the control group. However, ASC CMe alone increased vessel density after 7 days. Porcine skin-derived ECM hydrogels loaded with ASC secretome are noncytotoxic but demand optimization to significantly augment wound healing of skin flaps.
Palavras-chave
ASC, wound healing, ECM, skin flap, ASC secretome, hydrogels, adipose-derived stromal cells
URI
https://observatorio.fm.usp.br/handle/OPI/53867
Referências
  1. Cai YZ, 2019, AESTHET SURG J, V39, pNP504, DOI 10.1093/asj/sjz112
  2. Camargo CP, 2014, ACTA CIR BRAS, V29, P166, DOI 10.1590/S0102-86502014000300004
  3. Clause KC, 2013, CURR OPIN BIOTECH, V24, P830, DOI 10.1016/j.copbio.2013.04.011
  4. Crapo PM, 2011, BIOMATERIALS, V32, P3233, DOI 10.1016/j.biomaterials.2011.01.057
  5. Davis R E, 1999, Arch Facial Plast Surg, V1, P27, DOI 10.1001/archfaci.1.1.27
  6. Du P, 2017, ACTA BIOMATER, V54, P333, DOI 10.1016/j.actbio.2017.03.035
  7. Erickson GR, 2002, BIOCHEM BIOPH RES CO, V290, P763, DOI 10.1006/bbrc.2001.6270
  8. Feng CJ, 2020, J PLAST RECONSTR AES, V73, P598, DOI 10.1016/j.bjps.2019.10.001
  9. Foroglou P, 2016, WORLD J STEM CELLS, V8, P101, DOI 10.4252/wjsc.v8.i3.101
  10. Getova VE, 2019, ARTIF CELL NANOMED B, V47, P1693, DOI 10.1080/21691401.2019.1608215
  11. Gumus N, 2012, AESTHET PLAST SURG, V36, P1382, DOI 10.1007/s00266-012-9966-2
  12. Ha SS, 2020, ACS BIOMATER SCI ENG, V6, P4266, DOI 10.1021/acsbiomaterials.0c00657
  13. Halvorsen YDC, 2001, TISSUE ENG, V7, P729, DOI 10.1089/107632701753337681
  14. Halvorsen YDC, 2001, METABOLISM, V50, P407, DOI 10.1053/meta.2001.21690
  15. Hart K, 2006, LARYNGOSCOPE, V116, P522, DOI 10.1097/01.mlg.0000200792.67802.3b
  16. ISHIGURO N, 1994, ANN PLAS SURG, V32, P356, DOI 10.1097/00000637-199404000-00005
  17. Khan A, 2004, AM J PHYSIOL-REG I, V287, pR1219, DOI 10.1152/ajpregu.00143.2004
  18. Lee C, 2017, CYTOTHERAPY, V19, P1048, DOI 10.1016/j.jcyt.2017.06.007
  19. Lee WCC, 2006, CELLS TISSUES ORGANS, V183, P80, DOI 10.1159/000095512
  20. Liguori GR, 2020, FRONT BIOENG BIOTECH, V8, DOI 10.3389/fbioe.2020.00520
  21. Liguori TTA, 2021, BIOMED MATER, V16, DOI 10.1088/1748-605X/abcff9
  22. Lineaweaver WC, 2014, PLAST RECONSTR SURG, V133, p423E, DOI 10.1097/01.prs.0000438450.63153.25
  23. Martinez-Garcia FD, 2021, POLYMERS-BASEL, V13, DOI 10.3390/polym13183113
  24. MILTON SH, 1970, BRIT J SURG, V57, P502, DOI 10.1002/bjs.1800570705
  25. Mizuno H, 2002, PLAST RECONSTR SURG, V109, P199, DOI 10.1097/00006534-200201000-00030
  26. Morris AH, 2018, ACS APPL MATER INTER, V10, P41892, DOI 10.1021/acsami.8b08920
  27. Oh M, 2008, DERMATOL SURG, V34, P626, DOI 10.1111/j.1524-4725.2007.34118.x
  28. Park HJ, 2013, ANZ J SURG, V83, P354, DOI 10.1111/j.1445-2197.2012.06194.x
  29. Savitri C, 2020, J MATER CHEM B, V8, P9744, DOI 10.1039/d0tb01885f
  30. Spiekman M, 2017, J TISSUE ENG REGEN M, V11, P3220, DOI 10.1002/term.2213
  31. Theocharis AD, 2016, ADV DRUG DELIVER REV, V97, P4, DOI 10.1016/j.addr.2015.11.001
  32. van Dongen JA, 2019, J TISSUE ENG REGEN M, V13, P973, DOI 10.1002/term.2843
  33. Zhang P, 2018, BIOCHEM BIOPH RES CO, V495, P2249, DOI 10.1016/j.bbrc.2017.11.196
  34. Zuk PA, 2002, MOL BIOL CELL, V13, P4279, DOI 10.1091/mbc.E02-02-0105
  35. Zuk PA, 2001, TISSUE ENG, V7, P211, DOI 10.1089/107632701300062859

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - FM/MCG
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/04
Artigos e Materiais de Revistas Científicas - LIM/11