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A b s t r a c t : Keloid t i s s u e h a s been implanted i n t h e athymic nude mouse i n o r d e r t o develop a n experimental animal model f o r t h e s t u d y o f human k e l o i d s and h y p e r t r o p h i c s c a r s . Untreated k e l o i d t i s s u e s maintained e s s e n t i a l l y t h e same morphological p a t t e r n s and glycosaminoglycan d i s t r i b u t i o n s f o r a t l e a s t 60 days a f t e r i m p l a n t a t i o n i n t h e athymic mice. Normal human s k i n implanted i n t h e same way was maintained w i t h o u t change i n glycosaminog l y c a n d i s t r i b u t i o n o r morphologic c h a r a c t e r i s t i c s . W e s u g g e s t t h a t t h i s model may be u s e f u l f o r b a s i c r e s e a r c h of k e l o i d s and h y p e r t r o p h i c s c a r s i n t h a t it w i l l a l l o w s t u d i e s o f morphologic, biochemical and t h e r a p e u t i c i n t e r r e l a t i o n s h i p s under c o n t r o l l e d c o n d i t i o n s . @ 1985 Society f o r Experimental Biology and Nedicine. _Introduction: Basic r e s e a r c h on k e l o i d s and h y p e r t r o p h i c s c a r s h a s been g r e a t l y hampered because of t h e absence o f s u i t a b l e animal models f o r t h e s e c o n d i t i o n s . Hypertrophic s c a r s have been d e s c r i b e d i n a number o f farm animals; however, none of t h e s e have proven t o be s i m i l a r t o human h y p e r t r o p h i c s c a r s o r k e l o i d s i n regard t o h i s t o l o g y , biochemistry, o r c l i n i c a l h i s t o r y ( 1 ) . Attempts have been made t o induce t h e s e l e s i o n s i n animals, p a r t i c u l a r l y i n swine ( 2 ) . However, t h e s e s c a r s have n o t been accepted a s s i m i l a r t o human hypert r o p h i c s c a r s o r k e l o i d s . Recently, i t occurred t o u s t h a t s i n c e normal and d i s e a s e d human s k i n may be i mp l a n t e d and maintained i n t h e athymic nude mouse ( 3 , 4 , 5 , 6 ) a n animal model might be developed f o r k e l o i d r e s e a r c h by implanting k e l o i d s i n athymic nude mice. Consequently, we implanted human k e l o i d t i s s u e i n athymic nude mice and have i n v e s t i g ag a t e d whether t h e maintained t i s s u e has t h e d i s t i n c t i v e h i s t o l o g i c a l a s p e c t s and t h e biochemical composit i o n o f t h e o r i g i n a l k e l o i d t i s s u e . Previous p u b l i c a t i o n s have d e s c r i b e d t h e c h a r a c t e r i s t i c microscopic appearance (7) and c h a r a c t e r i s t i c a l t e r a t i o n s o f t h e glycosaminoglycans ( 8 ) i n k e l o i d s and h y p e r t r o p h i c s c a r s . M a t e r i a l s and Methods: Athymic nude mice ( N~/ c o x ) were obtained from Labor a t o r y Supply Company, I n d i a n a p o l i s , Indiana. They were k e p t i n p r e s t e r il i z e d cages, one mouse t o a cage, and placed i n a laminar flow sterile bench (Labconco Corporation, Model 36000).

Studies have been made of the glycosaminoglycan (GAG) composition of implants of keloid and hypertrophic scars in athymic nude mice in order to evaluate these implants as a model for studies of causation and therapy of these abnormal human scars. Changes in weight of implanted tissue were also recorded. Pieces of keloid, hypertrophic scar or normal human skin were placed in subcutaneous pockets of athymic nude mice and left for various times up to 246 days. The uronic acid content of the scar implants did not change significantly until after 80 days when the level decreased; the uronic acid level of normal skin increased slightly during the 110 days studied. The initially high percentage of chondroitin-4-sulfate of keloid and hypertrophic scar tissue decreased in the implants (averaging a 50% decrease at 164 days for keloids and at 176 days for hypertrophic scars). The average weight of the scar implants increased slightly after implantation and then decreased when expressed either as wet or dry weight. The regression lines of weight on time indicated an average loss of 50% dry weight at 66 days for keloid implants and 68 days for hypertrophic scars. Normal human skin increased in net weight until 20 days and dry weight until 40 days and then decreased, losing about 20% of weight (either wet or dry) at 110 days. On the basis of the glycosaminoglycan changes, the model should be useful for short term studies of therapy and causation.