FGF-7 expression enhances the performance of bioengineered skin

被引:37
作者
Erdag, G
Medalie, DA
Rakhorst, H
Krueger, GG
Morgan, JR
机构
[1] Brown Univ, Ctr Biomed Engn, Providence, RI 02912 USA
[2] Brown Univ, Biomed Ctr, Dept Mol Pharmacol Physiol & Biotechol, Providence, RI 02912 USA
[3] Massachusetts Gen Hosp, Ctr Engn Med & Surg, Boston, MA 02114 USA
[4] Harvard Univ, Sch Med, Boston, MA 02114 USA
[5] Shriners Hosp Children, Boston, MA 02114 USA
[6] Univ Utah, Hlth Sci Ctr, Dept Dermatol, Salt Lake City, UT 84132 USA
关键词
fibroblast growth factor; skin; wound healing; vascularization; infection; tissue engineering;
D O I
10.1016/j.ymthe.2004.04.013
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 0836 [生物工程]; 090102 [作物遗传育种]; 100705 [微生物与生化药学];
摘要
To improve the performance of bioengineered skin, we used a recombinant retrovirus encoding FGF-7 to modify diploid human keratinocytes genetically. Control or FGF-7-expressing keratinocytes were seeded onto acellular human dermis to form bioengineered skin. Gene-modified skin secreted significant levels of FGF-7 and formed a thicker and hyperproliferative epidermis with about four times the number of cells per square centimeter. Secretion of an endogenous trophic factor, VEGF, was increased similar to5-fold. Migration of FGF-7-expressing keratinocytes was stimulated as was the self-healing of bioengineered skin expressing FGF-7. When tested in a bacterial infection model, the antimicrobial properties of FGF-7-expressing skin were increased >500-fold against both gram-negative and gram-positive bacteria. After transplantation to full-thickness wounds on athymic mice, skin expressing FGF-7 was revascularized more rapidly. These results demonstrate that genetic modification can be used to enhance performance and that expression of FGF-7 augments several properties important to the wound-healing properties of bioengineered skin.
引用
收藏
页码:76 / 85
页数:10
相关论文
共 30 条
[1]
KERATINOCYTE GROWTH-FACTOR - A FIBROBLAST GROWTH-FACTOR FAMILY MEMBER WITH UNUSUAL TARGET-CELL SPECIFICITY [J].
AARONSON, SA ;
BOTTARO, DP ;
MIKI, T ;
RON, D ;
FINCH, PW ;
FLEMING, TP ;
AHN, J ;
TAYLOR, WG ;
RUBIN, JS .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1991, 638 :62-77
[2]
Keratinocyte growth factor induces hyperproliferation and delays differentiation in a skin equivalent model system [J].
Andreadis, ST ;
Hamoen, KE ;
Yarmush, ML ;
Morgan, JR .
FASEB JOURNAL, 2001, 15 (06) :898-906
[3]
IN-VIVO TRANSFER AND EXPRESSION OF A HUMAN EPIDERMAL GROWTH-FACTOR GENE ACCELERATES WOUND REPAIR [J].
ANDREE, C ;
SWAIN, WF ;
PAGE, CP ;
MACKLIN, MD ;
SLAMA, J ;
HATZIS, D ;
ERIKSSON, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (25) :12188-12192
[4]
LIVING TISSUE FORMED INVITRO AND ACCEPTED AS SKIN-EQUIVALENT TISSUE OF FULL THICKNESS [J].
BELL, E ;
EHRLICH, HP ;
BUTTLE, DJ ;
NAKATSUJI, T .
SCIENCE, 1981, 211 (4486) :1052-1054
[5]
Boyce S T, 1996, Tissue Eng, V2, P255, DOI 10.1089/ten.1996.2.255
[6]
Targeted expression of insulin-like growth factor to human keratinocytes: Modification of the autocrine control of keratinocyte proliferation [J].
Eming, SA ;
Snow, RG ;
Yarmush, ML ;
Morgan, JR .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1996, 107 (01) :113-120
[7]
Genetically modified human keratinocytes overexpressing PDGF-A enhance the performance of a composite skin graft [J].
Eming, SA ;
Medalie, DA ;
Tompkins, RG ;
Yarmush, ML ;
Morgan, JR .
HUMAN GENE THERAPY, 1998, 9 (04) :529-539
[8]
Regulation of the spatial organization of mesenchymal connective tissue -: Effects of cell-associated versus released isoforms of platelet-derived growth factor [J].
Eming, SA ;
Yarmush, ML ;
Krueger, GG ;
Morgan, JR .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 154 (01) :281-289
[9]
Interleukin-1α and interleukin-6 enhance the antibacterial properties of cultured composite keratinocyte grafts [J].
Erdag, G ;
Morgan, JR .
ANNALS OF SURGERY, 2002, 235 (01) :113-124
[10]
Wounding of bioengineered skin: Cellular and molecular aspects after injury [J].
Falanga, V ;
Isaacs, C ;
Paquette, D ;
Downing, G ;
Kouttab, N ;
Butmarc, J ;
Badiavas, E ;
Hardin-Young, J .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2002, 119 (03) :653-660