Regeneration of skeletal and cardiac muscle in mammals: do nonprimate models resemble human pathology?

Most of the available information regarding the regenerative potential and compensatory remodeling of mammalian tissues has been obtained from nonprim ate animals, mainly rodent experimental models. The increasing use of trans genic mice for studies of the mechanisms controlling organogenesis and rege neration also requires a clear understanding of their applicability as expe rimental models for studies of similar processes in humans and other mammal s. Application of modern cell biology methods to studies of regenerative pr ocesses has provided new insights into similarity and differences in cellul ar responses to injury in the tissues of different mammalian species. Durin g more than 200-million years of progressive divergent evolution of mammals , cellular mechanisms of tissue regeneration and compensatory remodeling ev olved together with increasingly adaptive functional specialization and str uctural complexity of mammalian tissues and organs. Rodents represent a phy logenetically ancient order of mammals that has conservatively retained a n umber of morphofunctional characteristics of early representatives of this class, which include enhanced regenerative capacity of tissues. A comparati ve analysis of regenerative processes in skeletal and cardiac muscle, as we ll as in several other mammalian tissues, shows that time courses and inten sities of regeneration in response to the same type of injury vary even wit hin taxonomically related species (e.g., rat, mouse, and hamster). The warm bloodedness of mammals facilitated the development of more complex mechani sms of metabolic, immune, and neurohumoral regulation, which resulted in a stronger dependence of regenerative processes on vascularization and innerv ation. For this reason, interspecies modifications of regenerative response s are limited by the capacity of the animal to resorb rapidly the foci of n ecrosis and to revascularize and reinnervate the volume of the regenerating tissue. These differences, among other factors, result in significantly lo wer rates of reparative regeneration in mammals possessing larger body size s than rodents. A review of these data strongly indicates that the phylogen etic age and biological differences between different species should be tak en into account before extrapolation of regenerative properties of nonprima te tissues on the regenerative responses in the primates.