The high morbidity and mortality associated with massive burns are mainly due to bacterial invasion of open wounds. Early closure of burn wounds can prevent this complication. In massive burns, however, donor sites for autologous skin grafts are severely limited, and temporary coverings must be employed until healed donor sites become available. We have recently demonstrated that cultured keratinocyte sheets generated from a small biopsy of unburned skin can be used successfully as autografts in the treatment of massive acute burns. Grafts provide permanent wound closure within a three week period, the length of time required to generate the cultured epithelial sheets. Once placed on the wound bed, cultured grafts attach and differentiate into a normally stratified epidermis within one to two weeks. Preliminary results from long-term follow-up biopsies indicate that the skin regenerated from cultured grafts compares favorably with meshed split-thickness skin grafts of comparable age. The proposed project is a morphologic, morphometric, and immunohistochemical study of cultured grafts in vivo. The study has two major goals: 1) to provide a better understanding of the long-term behavior of the grafts in order to objectively evaluate their clinical usefulness, and 2) to take advantage of this new human biologic system to investigate problems of basic scientific interest in the fields of epidermal physiology and wound healing.
The specific aims of the study are to examine changes associated with healing and regeneration of skin from cultured grafts in comparison with conventional split-thickness autografts. Donor site-specific differences in graft healing and differentiation will be examined, and the phenomena associated with epidermal-connective tissue attachment will be studied by the use of monoclonal antibodies directed against basement membrane components and by electron microscopy. Epithelial differentiation will be analyzed using antibodies against different classes of cytoplasmic keratins. Part of the study will examine colonization of grafts by epidermal dendritic cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM035242-04
Application #
3287642
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1986-04-05
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Compton, C C; Nadire, K B; Regauer, S et al. (1998) Cultured human sole-derived keratinocyte grafts re-express site-specific differentiation after transplantation. Differentiation 64:45-53
Compton, C C; Tong, Y; Trookman, N et al. (1995) Transforming growth factor alpha gene expression in cultured human keratinocytes is unaffected by cellular aging. Arch Dermatol 131:683-90
Compton, C C; Press, W; Gill, J M et al. (1995) The generation of anchoring fibrils by epidermal keratinocytes: a quantitative long-term study. Epithelial Cell Biol 4:93-103
Compton, C C; Rizk, I; Regauer, S et al. (1994) The effect of bromocryptine-induced hypoprolactinemia on xenogeneic and allogeneic skin graft survival in a mouse model. J Burn Care Rehabil 15:393-400
Compton, C; Tong, T; Trookman, N et al. (1994) TGF-beta 1 gene expression in cultured human keratinocytes does not decrease with biologic age. J Invest Dermatol 103:127-33
Compton, C C; Hickerson, W; Nadire, K et al. (1993) Acceleration of skin regeneration from cultured epithelial autografts by transplantation to homograft dermis. J Burn Care Rehabil 14:653-62
Green, H A; Burd, E E; Nishioka, N S et al. (1993) Skin graft take and healing following 193-nm excimer, continuous-wave carbon dioxide (CO2), pulsed CO2, or pulsed holmium: YAG laser ablation of the graft bed. Arch Dermatol 129:979-88
Compton, C C (1992) Current concepts in pediatric burn care: the biology of cultured epithelial autografts: an eight-year study in pediatric burn patients. Eur J Pediatr Surg 2:216-22
Compton, C C; Regauer, S; Seiler, G R et al. (1990) Human Merkel cell regeneration in skin derived from cultured keratinocyte grafts. Lab Invest 63:233-41
Regauer, S; Compton, C (1990) Cultured porcine epithelial grafts: an improved method. J Invest Dermatol 94:230-4

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