REJUVENESCENCE AND DEATH 295 



multinucleate " giant cells" (Fig. 122), and these do not give rise to 

 new fibrillar substance, but usually die sooner or later. Even if 

 Minot is correct in maintaining that the fibrillar substance has no 

 capacity for regeneration, it is of interest to note that the new 

 fibrillar substance seems to arise in continuity with the old, while 

 isolated cells apparently do not produce fibrillar substance. 



The conclusion that there is no dedifferentiation involved in 

 such cases is, I believe, not warranted by the facts. The point of 

 importance is that during the earlier stages of their developmental 

 history the muscle cells produced granular cytoplasm and nuclear 

 substance and grew and divided, but later began to give rise to 

 fibrillar substance and the proportion of this substance to the 

 nuclei and granular " undifferentiated " cytoplasm increased enor- 

 mously. After injury, however, the activity of the muscle cells 

 changes, and they produce more granular cytoplasm and more 

 nuclear substance. In short, they have returned to a kind of 

 activity characteristic of early stages of embryonic development. 

 What is this if it is not dedifferentiation ? The fact that the old 

 fibrillar substance degenerates instead of regenerating is quite 

 irrelevant. The question is not whether all parts of the cells are 

 capable of regeneration, but whether the cells can again resume a 

 kind of activity characteristic of an earlier stage of development, 

 and the process of regeneration of muscle and various other tissues 

 in man and the higher animals leaves no doubt that they possess 

 this capacity. Even in the outgrowth of new nerve fibers from the 

 central stump of a cut nerve there is a return to a process of growth 

 and development which is normally characteristic of an earlier 

 stage of development. Champy maintains that dedifferentiation 

 occurs in tissues cultivated outside the organism in nutritive 

 media the method often termed explantation and has described 

 at length the changes in cultures of kidney cells. 1 Regression and 

 dedifferentiation certainly occur to a greater or less extent in most 

 tissues of man and the higher animals, but the apparent inability 

 of the cells of one tissue to give rise to other tissues indicates that, 



1 See Champy, '13, '14, and earlier papers which are included, together with 

 many other references bearing upon this question, in the bibliographic lists of these 

 papers. 



