IV EPITHELIALIZATION 679 



membrane; b) mobilization of epidermal cells in a wave-like fashion extending 

 from the wound edge; c) emigration of the epidermal sheet; d) simultaneous 

 cessation of movement when the wound was covered. Both detachment and 

 mobilization begin at the wound margin and extend peripherally; cessation 

 of cell migration, however, occurs simultaneously throughout the migrating 

 sheet. The fact that some component cells are able to reverse direction when a 

 closer border is available and others cells remain stationary is strong evidence against 

 the theory that mass movement is the only important factor in this phenomenon. 



[v) Layers involved in migration. Considerable confusion exists as to which cell 

 layers are involved in migration. Eycleshymer (1907), for example, reported that all 

 layers to Necturus larval epidermis take part, whereas Uhlenhuth (1914) found that 

 it was limited chiefly to the basal cells. Cole (1922) observed that the epidermis of 

 frog wounds, which is initially one cell in thickness, later increased due to subsequent 

 migration. Similar findings have been noted in skin grafts on frogs (Herrick, 1932). 



Human skin has been studied both in vivo and in vitro. Matoltsy (1955) produced 

 wounds in the center of cultured skin explants, which healed by migration of the 

 basal cell and stratum germinativum layers. No cell divisions were found at the 

 wound edge and the rete pegs became flattened, suggesting that their cells were 

 used in migration. Bishop (1945) in studying forearm wounds at various depths 

 concluded the Malpighian layer migrated while the basal layer remained sta- 

 tionary. Hartwell (1929, 1955) has repeatedly emphasized that all cell layers are 

 active in migration, although the majority of cells come from the middle and 

 uppermost layers. He believes that the basal layer is formed by rounding and 

 realignment of the lowermost cells which does not begin until migration ceases. 



Present evidence indicates that migrating epithelial elements retain all of their 

 morphological characteristics and do not dedifferentiate, as claimed by Eycles- 

 hymer (1907) and Poynter (1919). There is no support for Levander's theory 

 (1950) that epithelialization is the result of diflferentiation of undifferentiated cells 

 in the superficial portion of the granulation tissue. 



(vi) The role of mitosis. The role of mitosis in epithelialization is now well under- 

 stood. It was thought originally that the entire epidermal sheet arose as a result of 

 increased cell division (Eberth, 1891; Von Bardeleben, 1901), but it has been 

 firmly established that mitoses only occur after initial migration is well underway 

 (Oppel, 191 3; Osowski, 1914; Poynter, 1919; Gurwitsch, 1926; Arey, 1932; 

 Herrick, 1932; Arey and Cavode, 1943; Mann, 1944; Pepper, 1954). An actual 

 decline in mitotic rate may occur during the early stage of epithelialization (Loeb 

 1898; Marchand, 1901; Werner, 1902; Arey and Cavode, 1943; BuUough, 1946). 

 Akaiwa (1919a, b) found that the mitotic rate increased rapidly at the wound 

 margin in old epithelium as long as it was incompletely epithelialized. The nature 

 of the stimulus for mitosis or the manner in which it is transmitted to the epithelial 

 cells at the wound edge is obscure. It does not appear to be related to loss of contact 

 with adjacent cells since this promotes migration rather than cell division. 



The mitotic activity of cells in the migrating sheet is uniformly low or absent 

 while movement is in progress. Hartwell (1929, 1955) believes that the onset of 



Literature p, 703 



