The Use of Athymic Nude Mice for the Study of Human Keloids

Abstract

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).

Exogenous Transforming Growth Factor β2 Modulates Collagen I and Collagen III Synthesis in Proliferative Scar Xenografts in Nude Rats

“…A major reason for this has been that proliferative scar formation is limited to humans and is difficult to study systematically. This has been overcome by using the congenitally athymic nude mouse [3][4][5] and rat [6]. Recently, a new in vivo model of human proliferative scar explanted to a sandwich-island flap, maintained on an isolated accessible vasculature in a "nude" rat, was developed by our laboratory.…”

A novel model of humanised keloid scarring in mice

“…However, few keloid scar models have been developed in animals that mimic human keloid pathology (7,8). The scar model of the nude mouse was first established by Sheltlar et al, who found that the scar pieces transplanted to the subcutaneous of the nude mouse was able to be maintained for long time and showed similar histological properties in the body (9). However, the process of model establishment was complicated and apt to have deviation.…”

Experimental Keloid Scar Models: A Review of Methodological Issues

“…Chronologically, the athymic mouse model was developed ®rst, followed by the development of the athymic rat model. 13,14 The merits of each model must be carefully considered prior to experimentation. Tables II and III outline the characteristics and advantages and disadvantages of each athymic rodent model.…”