The effects of microenvironment on wound healing by keratinocytes derived from mesenchymal stem cells

Yi-Han Lin, Keng-Yen Fu, Po-Da Hong, Hsu Ma, Nien-Hsien Liou, Kuo-Hsing Ma, Jiang-Chuan Liu, Kun-Lun Huang, Lien-Guo Dai, Shun-Cheng Chang, Yi-Hsin Chan, Shyi-Gen Chen, Tim-Mo Chen, Niann-Tzyy Dai

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

ABSTRACT: Embryonic stem cells (ESCs) are pluripotent cells that can differentiate into various cell types, including keratinocyte-like cells, within suitable microniches. In this study, we aimed to investigate the effects of culture media, cell coculture, and a tissue-engineering biocomposite on the differentiation of mouse ESCs (MESCs) into keratinocyte-like cells and applied these cells to a surgical skin wound model. MESCs from BALB/c mice (ESC26GJ), which were transfected using pCX-EGFP expressing green fluorescence, were used to track MESC-derived keratinocytes. Weak expression of the keratinocyte early marker Cytokeratin 14 (CK-14) was observed up to 12 days when MESCs were cultured in a keratinocyte culture medium on tissue culture plastic and on a gelatin/collagen/polycaprolactone (GCP) biocomposite. MESCs cocultured with human keratinocyte cells (HKCs) also expressed CK-14, but did not express CK-14 when cocultured with human fibroblast cells (HFCs). Furthermore, CK-14 expression was observed when MESCs were cocultured by seeding HKCs or HFCs on the same or opposite side of the GCP biocomposite. The highest CK-14 expression was observed by seeding MESCs and HKCs on the same side of the GCP composite and with HFCs on the opposite side. To verify the effectiveness of wound healing in vivo, adipose-derived stem cells were applied to treat surgical wounds in nude mice. An obvious epidermis multilayer and better collagen deposition during wound healing were observed, as assessed by Masson staining. This study demonstrated the potential of keratinocyte-like differentiation from mesenchymal stem cells for use in promoting wound closure and skin regeneration. Copyright © 2013 Lippincott Williams & Wilkins.
Original languageEnglish
Pages (from-to)S67-S74
JournalAnnals of Plastic Surgery
Volume71
Issue numberSUPPL.1
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Mesenchymal Stromal Cells
Keratinocytes
Wound Healing
Keratin-14
Collagen
Gelatin
Fibroblasts
Culture Media
Skin
Tissue Engineering
Embryonic Stem Cells
Coculture Techniques
Nude Mice
Epidermis
Plastics
Regeneration
Stem Cells
Fluorescence
Staining and Labeling

Keywords

  • gelatin/collagen/polycaprolactone (GCP) biocomposite
  • human fibroblast cells (HFCs)
  • human keratinocyte cells (HKCs)
  • mesenchymal stem cells
  • mice embryonic stem cells (MESCs)
  • skin regeneration
  • animal
  • article
  • cell differentiation
  • coculture
  • culture medium
  • cytology
  • fibroblast
  • human
  • keratinocyte
  • mesenchymal stroma cell
  • metabolism
  • methodology
  • mouse
  • nude mouse
  • physiology
  • tissue engineering
  • wound healing
  • Animals
  • Cell Differentiation
  • Coculture Techniques
  • Culture Media
  • Fibroblasts
  • Humans
  • Keratinocytes
  • Mesenchymal Stromal Cells
  • Mice
  • Mice, Nude
  • Tissue Engineering
  • Wound Healing

Cite this

The effects of microenvironment on wound healing by keratinocytes derived from mesenchymal stem cells. / Lin, Yi-Han; Fu, Keng-Yen; Hong, Po-Da; Ma, Hsu; Liou, Nien-Hsien; Ma, Kuo-Hsing; Liu, Jiang-Chuan; Huang, Kun-Lun; Dai, Lien-Guo; Chang, Shun-Cheng; Chan, Yi-Hsin; Chen, Shyi-Gen; Chen, Tim-Mo; Dai, Niann-Tzyy.

In: Annals of Plastic Surgery, Vol. 71, No. SUPPL.1, 2013, p. S67-S74.

Research output: Contribution to journalArticle

Lin, Y-H, Fu, K-Y, Hong, P-D, Ma, H, Liou, N-H, Ma, K-H, Liu, J-C, Huang, K-L, Dai, L-G, Chang, S-C, Chan, Y-H, Chen, S-G, Chen, T-M & Dai, N-T 2013, 'The effects of microenvironment on wound healing by keratinocytes derived from mesenchymal stem cells', Annals of Plastic Surgery, vol. 71, no. SUPPL.1, pp. S67-S74. https://doi.org/10.1097/SAP.0000000000000045
Lin, Yi-Han ; Fu, Keng-Yen ; Hong, Po-Da ; Ma, Hsu ; Liou, Nien-Hsien ; Ma, Kuo-Hsing ; Liu, Jiang-Chuan ; Huang, Kun-Lun ; Dai, Lien-Guo ; Chang, Shun-Cheng ; Chan, Yi-Hsin ; Chen, Shyi-Gen ; Chen, Tim-Mo ; Dai, Niann-Tzyy. / The effects of microenvironment on wound healing by keratinocytes derived from mesenchymal stem cells. In: Annals of Plastic Surgery. 2013 ; Vol. 71, No. SUPPL.1. pp. S67-S74.
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abstract = "ABSTRACT: Embryonic stem cells (ESCs) are pluripotent cells that can differentiate into various cell types, including keratinocyte-like cells, within suitable microniches. In this study, we aimed to investigate the effects of culture media, cell coculture, and a tissue-engineering biocomposite on the differentiation of mouse ESCs (MESCs) into keratinocyte-like cells and applied these cells to a surgical skin wound model. MESCs from BALB/c mice (ESC26GJ), which were transfected using pCX-EGFP expressing green fluorescence, were used to track MESC-derived keratinocytes. Weak expression of the keratinocyte early marker Cytokeratin 14 (CK-14) was observed up to 12 days when MESCs were cultured in a keratinocyte culture medium on tissue culture plastic and on a gelatin/collagen/polycaprolactone (GCP) biocomposite. MESCs cocultured with human keratinocyte cells (HKCs) also expressed CK-14, but did not express CK-14 when cocultured with human fibroblast cells (HFCs). Furthermore, CK-14 expression was observed when MESCs were cocultured by seeding HKCs or HFCs on the same or opposite side of the GCP biocomposite. The highest CK-14 expression was observed by seeding MESCs and HKCs on the same side of the GCP composite and with HFCs on the opposite side. To verify the effectiveness of wound healing in vivo, adipose-derived stem cells were applied to treat surgical wounds in nude mice. An obvious epidermis multilayer and better collagen deposition during wound healing were observed, as assessed by Masson staining. This study demonstrated the potential of keratinocyte-like differentiation from mesenchymal stem cells for use in promoting wound closure and skin regeneration. Copyright {\circledC} 2013 Lippincott Williams & Wilkins.",
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author = "Yi-Han Lin and Keng-Yen Fu and Po-Da Hong and Hsu Ma and Nien-Hsien Liou and Kuo-Hsing Ma and Jiang-Chuan Liu and Kun-Lun Huang and Lien-Guo Dai and Shun-Cheng Chang and Yi-Hsin Chan and Shyi-Gen Chen and Tim-Mo Chen and Niann-Tzyy Dai",
note = "被引用次數:1 Export Date: 21 March 2016 CODEN: APCSD 通訊地址: Dai, N.-T.; Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Rd, Nei-Hu District, Taipei 114, Taiwan; 電子郵件: niantzyy_dai@hotmail.com 化學物質/CAS: Culture Media 參考文獻: Friel, R., Van Der Sar, S., Mee, P.J., Embryonic stem cells: Understanding their history, cell biology and signalling (2005) Adv Drug Deliv Rev., 57, pp. 1894-1903; Evan, M.J., Kaufman, M.H., Establishment in culture of pluripotential cells from mouse embryos (1981) Nature., 292, pp. 154-156; Robertson, E.J., (1987) Embryo Derived Stem Cell Lines, pp. 71-112. , In: Teratocarcinomas And Embryonic Stem Cells: A Practical Approach. Oxford London: IRL Press; Fuchs, E., Epidermal differentiation: The bare essentials (1990) J Cell Biol., 111, pp. 2807-2814; Rennekampff, H.O., Hansbrough, J.F., Kiessig, V., Bioactive interleukin-8 is expressed in wounds and enhances wound healing (2000) J Surg Res., 93, pp. 41-54; Gurtner, G.C., Werner, S., Barrandon, Y., Wound repair and regeneration (2008) Nature., 453, pp. 314-321; Metallo, C.M., Mohr, J.C., Detzel, C.J., Engineering the stem cell microenvironment (2007) Biotechnol Prog., 23, pp. 18-23; Levenberg, S., Huang, N.F., Lavik, E., Differentiation of human embryonic stem cells on three-dimensional polymer scaffolds (2003) Proc Natl Acad Sci U S A., 100, pp. 12741-12746; Inanc, B., Elcin, A.E., Elcin, Y.M., Human embryonic stem cell differentiation on tissue engineering scaffolds: Effects of NGF and retinoic acid induction (2008) Tissue Eng Part A., 14, pp. 955-964; Hewitt, K.J., Shamis, Y., Carlson, M.W., Three-dimensional epithelial tissues generated from human embryonic stem cells (2009) Tissue Eng Part A., 15, pp. 3417-3426; Lin, H.T., Kao, C.L., Lee, K.H., Enhancement of insulin-producing cell differentiation from embryonic stem cells using pax4-nucleofection method (2007) World J Gastroenterol., 13, pp. 1672-1679; Dai, N.T., Yeh, M.K., Chiang, C.H., Human single-donor composite skin substitutes based on collagen and polycaprolactone copolymer (2009) Biochem Biophys Res Commun., 386, pp. 21-25; Ning, F., Guo, Y., Tang, J., Differentiation of mouse embryonic stem cells into dental epithelial-like cells induced by ameloblasts serum-free conditioned medium (2010) Biochem Biophys Res Commun., 394, pp. 342-347; Huang, S.P., Hsu, C.C., Chang, S.C., Adipose-derived stem cells seeded on acellular dermal matrix grafts enhance wound healing in a murine model of a full-Thickness defect (2012) Ann Plast Surg., 69, pp. 656-662; Roeder, H.A., Cramer, S.F., Leppert, P.C., A look at uterine wound healing through a histopathological study of uterine scars (2012) Reprod Sci., 19, pp. 463-473; Ji, L., Allen-Hoffmann, B.L., De Pablo, J.J., Generation and differentiation of human embryonic stem cell-derived keratinocyte precursors (2006) Tissue Eng., 12, pp. 665-679; Coraux, C., Hilmi, C., Rouleau, M., Reconstituted skin from murine embryonic stem cells (2003) Curr Biol., 13, pp. 849-853; Murry, C.E., Keller, G., Differentiation of embryonic stem cells to clinically relevant populations: Lessons from embryonic development (2008) Cell., 132, pp. 661-680; Itoh, M., Kiuru, M., Cairo, M.S., Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells (2011) Proc Natl Acad Sci U S A., 108, pp. 8797-8802; Dabelsteen, S., Hercule, P., Barron, P., Epithelial cells derived from human embryonic stem cells display p16INK4A senescence, hypermotility, and differentiation properties shared by many P63+ somatic cell types (2009) Stem Cells., 27, pp. 1388-1399",
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doi = "10.1097/SAP.0000000000000045",
language = "English",
volume = "71",
pages = "S67--S74",
journal = "Annals of Plastic Surgery",
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TY - JOUR

T1 - The effects of microenvironment on wound healing by keratinocytes derived from mesenchymal stem cells

AU - Lin, Yi-Han

AU - Fu, Keng-Yen

AU - Hong, Po-Da

AU - Ma, Hsu

AU - Liou, Nien-Hsien

AU - Ma, Kuo-Hsing

AU - Liu, Jiang-Chuan

AU - Huang, Kun-Lun

AU - Dai, Lien-Guo

AU - Chang, Shun-Cheng

AU - Chan, Yi-Hsin

AU - Chen, Shyi-Gen

AU - Chen, Tim-Mo

AU - Dai, Niann-Tzyy

N1 - 被引用次數:1 Export Date: 21 March 2016 CODEN: APCSD 通訊地址: Dai, N.-T.; Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Rd, Nei-Hu District, Taipei 114, Taiwan; 電子郵件: niantzyy_dai@hotmail.com 化學物質/CAS: Culture Media 參考文獻: Friel, R., Van Der Sar, S., Mee, P.J., Embryonic stem cells: Understanding their history, cell biology and signalling (2005) Adv Drug Deliv Rev., 57, pp. 1894-1903; Evan, M.J., Kaufman, M.H., Establishment in culture of pluripotential cells from mouse embryos (1981) Nature., 292, pp. 154-156; Robertson, E.J., (1987) Embryo Derived Stem Cell Lines, pp. 71-112. , In: Teratocarcinomas And Embryonic Stem Cells: A Practical Approach. Oxford London: IRL Press; Fuchs, E., Epidermal differentiation: The bare essentials (1990) J Cell Biol., 111, pp. 2807-2814; Rennekampff, H.O., Hansbrough, J.F., Kiessig, V., Bioactive interleukin-8 is expressed in wounds and enhances wound healing (2000) J Surg Res., 93, pp. 41-54; Gurtner, G.C., Werner, S., Barrandon, Y., Wound repair and regeneration (2008) Nature., 453, pp. 314-321; Metallo, C.M., Mohr, J.C., Detzel, C.J., Engineering the stem cell microenvironment (2007) Biotechnol Prog., 23, pp. 18-23; Levenberg, S., Huang, N.F., Lavik, E., Differentiation of human embryonic stem cells on three-dimensional polymer scaffolds (2003) Proc Natl Acad Sci U S A., 100, pp. 12741-12746; Inanc, B., Elcin, A.E., Elcin, Y.M., Human embryonic stem cell differentiation on tissue engineering scaffolds: Effects of NGF and retinoic acid induction (2008) Tissue Eng Part A., 14, pp. 955-964; Hewitt, K.J., Shamis, Y., Carlson, M.W., Three-dimensional epithelial tissues generated from human embryonic stem cells (2009) Tissue Eng Part A., 15, pp. 3417-3426; Lin, H.T., Kao, C.L., Lee, K.H., Enhancement of insulin-producing cell differentiation from embryonic stem cells using pax4-nucleofection method (2007) World J Gastroenterol., 13, pp. 1672-1679; Dai, N.T., Yeh, M.K., Chiang, C.H., Human single-donor composite skin substitutes based on collagen and polycaprolactone copolymer (2009) Biochem Biophys Res Commun., 386, pp. 21-25; Ning, F., Guo, Y., Tang, J., Differentiation of mouse embryonic stem cells into dental epithelial-like cells induced by ameloblasts serum-free conditioned medium (2010) Biochem Biophys Res Commun., 394, pp. 342-347; Huang, S.P., Hsu, C.C., Chang, S.C., Adipose-derived stem cells seeded on acellular dermal matrix grafts enhance wound healing in a murine model of a full-Thickness defect (2012) Ann Plast Surg., 69, pp. 656-662; Roeder, H.A., Cramer, S.F., Leppert, P.C., A look at uterine wound healing through a histopathological study of uterine scars (2012) Reprod Sci., 19, pp. 463-473; Ji, L., Allen-Hoffmann, B.L., De Pablo, J.J., Generation and differentiation of human embryonic stem cell-derived keratinocyte precursors (2006) Tissue Eng., 12, pp. 665-679; Coraux, C., Hilmi, C., Rouleau, M., Reconstituted skin from murine embryonic stem cells (2003) Curr Biol., 13, pp. 849-853; Murry, C.E., Keller, G., Differentiation of embryonic stem cells to clinically relevant populations: Lessons from embryonic development (2008) Cell., 132, pp. 661-680; Itoh, M., Kiuru, M., Cairo, M.S., Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells (2011) Proc Natl Acad Sci U S A., 108, pp. 8797-8802; Dabelsteen, S., Hercule, P., Barron, P., Epithelial cells derived from human embryonic stem cells display p16INK4A senescence, hypermotility, and differentiation properties shared by many P63+ somatic cell types (2009) Stem Cells., 27, pp. 1388-1399

PY - 2013

Y1 - 2013

N2 - ABSTRACT: Embryonic stem cells (ESCs) are pluripotent cells that can differentiate into various cell types, including keratinocyte-like cells, within suitable microniches. In this study, we aimed to investigate the effects of culture media, cell coculture, and a tissue-engineering biocomposite on the differentiation of mouse ESCs (MESCs) into keratinocyte-like cells and applied these cells to a surgical skin wound model. MESCs from BALB/c mice (ESC26GJ), which were transfected using pCX-EGFP expressing green fluorescence, were used to track MESC-derived keratinocytes. Weak expression of the keratinocyte early marker Cytokeratin 14 (CK-14) was observed up to 12 days when MESCs were cultured in a keratinocyte culture medium on tissue culture plastic and on a gelatin/collagen/polycaprolactone (GCP) biocomposite. MESCs cocultured with human keratinocyte cells (HKCs) also expressed CK-14, but did not express CK-14 when cocultured with human fibroblast cells (HFCs). Furthermore, CK-14 expression was observed when MESCs were cocultured by seeding HKCs or HFCs on the same or opposite side of the GCP biocomposite. The highest CK-14 expression was observed by seeding MESCs and HKCs on the same side of the GCP composite and with HFCs on the opposite side. To verify the effectiveness of wound healing in vivo, adipose-derived stem cells were applied to treat surgical wounds in nude mice. An obvious epidermis multilayer and better collagen deposition during wound healing were observed, as assessed by Masson staining. This study demonstrated the potential of keratinocyte-like differentiation from mesenchymal stem cells for use in promoting wound closure and skin regeneration. Copyright © 2013 Lippincott Williams & Wilkins.

AB - ABSTRACT: Embryonic stem cells (ESCs) are pluripotent cells that can differentiate into various cell types, including keratinocyte-like cells, within suitable microniches. In this study, we aimed to investigate the effects of culture media, cell coculture, and a tissue-engineering biocomposite on the differentiation of mouse ESCs (MESCs) into keratinocyte-like cells and applied these cells to a surgical skin wound model. MESCs from BALB/c mice (ESC26GJ), which were transfected using pCX-EGFP expressing green fluorescence, were used to track MESC-derived keratinocytes. Weak expression of the keratinocyte early marker Cytokeratin 14 (CK-14) was observed up to 12 days when MESCs were cultured in a keratinocyte culture medium on tissue culture plastic and on a gelatin/collagen/polycaprolactone (GCP) biocomposite. MESCs cocultured with human keratinocyte cells (HKCs) also expressed CK-14, but did not express CK-14 when cocultured with human fibroblast cells (HFCs). Furthermore, CK-14 expression was observed when MESCs were cocultured by seeding HKCs or HFCs on the same or opposite side of the GCP biocomposite. The highest CK-14 expression was observed by seeding MESCs and HKCs on the same side of the GCP composite and with HFCs on the opposite side. To verify the effectiveness of wound healing in vivo, adipose-derived stem cells were applied to treat surgical wounds in nude mice. An obvious epidermis multilayer and better collagen deposition during wound healing were observed, as assessed by Masson staining. This study demonstrated the potential of keratinocyte-like differentiation from mesenchymal stem cells for use in promoting wound closure and skin regeneration. Copyright © 2013 Lippincott Williams & Wilkins.

KW - gelatin/collagen/polycaprolactone (GCP) biocomposite

KW - human fibroblast cells (HFCs)

KW - human keratinocyte cells (HKCs)

KW - mesenchymal stem cells

KW - mice embryonic stem cells (MESCs)

KW - skin regeneration

KW - animal

KW - article

KW - cell differentiation

KW - coculture

KW - culture medium

KW - cytology

KW - fibroblast

KW - human

KW - keratinocyte

KW - mesenchymal stroma cell

KW - metabolism

KW - methodology

KW - mouse

KW - nude mouse

KW - physiology

KW - tissue engineering

KW - wound healing

KW - Animals

KW - Cell Differentiation

KW - Coculture Techniques

KW - Culture Media

KW - Fibroblasts

KW - Humans

KW - Keratinocytes

KW - Mesenchymal Stromal Cells

KW - Mice

KW - Mice, Nude

KW - Tissue Engineering

KW - Wound Healing

U2 - 10.1097/SAP.0000000000000045

DO - 10.1097/SAP.0000000000000045

M3 - Article

VL - 71

SP - S67-S74

JO - Annals of Plastic Surgery

JF - Annals of Plastic Surgery

SN - 0148-7043

IS - SUPPL.1

ER -