I INTRODUCTION 665 



healing. Levander (1950), however, believed the epithelium arose in part, at 

 least, by differentiation from underlying granulation tissue, and Maximow (1902) 

 and more recently others (Allgower, 1956) have felt that the blood stream 

 contains certain cells capable of differentiation into fibroblasts. The dilemma 

 concerning the source of cells for either the blastema or granulation tissue is due 

 to the fact that, so far, it has been impossible to identify individual or groups of 

 cells for a sufficiently long period to follow their ultimate fate, as was done by 

 Vogt (1925) in mapping the presumptive areas for amphibian embryos. Numerous 

 experiments involving transplantation of whole blastemas and deletion of varying 

 portions of the regenerate have definitely proven the presence of undifferentiated 

 cells, but their source still remains obscure. It is conceivable that a solution 

 to this problem may afford an entirely different approach to our understanding 

 of wound healing. 



The factors determining which type of epimorphysis occurs are : the position 

 of the animal in the phylogenetic scale, its stage of development and the extent 

 and location of the wound. In general, regeneration is restricted to certain 

 amphibia and various lower forms. Species possessing the capacity to regenerate 

 in certain areas, such as extremities and tail (Triturus), are able to undergo wound 

 healing in other parts of the body. 



It should be stressed that epimorphysis by either process is primarily a problem 

 of cell movement with mitoses occurring later. In this respect, it bears strong 

 resemblance to embryonic development, as pointed out by Medawar (1945). 

 In regeneration the initial stages do not involve cell division, the epithelium 

 migrates over the defect and dedifferentiation proceeds accompanied by phago- 

 cytosis. Cell division does, however, seem to be necessary to arrest dedifferentia- 

 tion ; the subsequent formation of a blastema is not accompanied by any sudden 

 increase in mitotic rate (Needham, 1952). Similarly, during wound healing 

 epithelialization consists primarily of cell movement with mitoses at the wound 

 edge occurring only later to make up the cell deficit. Such wounds initially manifest 

 a large increase in the number of cellular elements which is not accompanied by 

 cell division. This phenomenon was recognized by Maximow (1902) and repre- 

 sents a migration of phagocytic cells to the wound area via the vascular pathway. 

 The subsequent formation of granulation tissue is brought about by local mi- 

 gration of endothelial and fibroblastic elements. In embryonic development 

 migration of cell masses is a frequent occurrence, beginning with the initial 

 invagination at the upper lip of the blastopore and continuing during the 

 development of nearly all body organs. These mass movements are not accom- 

 panied by sudden rises in mitotic rate, hence formation of any bodily structure, 

 whether primarily or secondarily, follows a similar pattern. Migration does 

 not result from passive displacement but is an active process. The stimulus 

 which initiates this mass movement of cells at certain critical periods in 

 development or repair remains obscure. Menkin's (1940, 1953, 1956) work has 

 done much to explain the force controlling specialized phagocytic cells and 

 directing their movement to the site of injury. The factors controlling local 

 migration are still unknown. It is obvious that in the adult organism migration 

 of cell masses takes place only following the production of a defect. Weiss 



Lilerature p. yo3 



