November 28, 1919] 



SCIENCE 



503 



calls forth an emigration of epidermal cells 

 into the wound. Secondarily, cell prolifera- 

 tion by mitosis and a contraction of fibrous 

 tissue takes place and these three processes 

 contribute to the wound closure. Under cer- 

 tain conditions the intensity of cell migration 

 depends upon the size of the wound; and the 

 contraction of the wound, depending in all 

 probability on the contraction of the fibrous 

 tissue and the number of retracting fibers 

 being greater in the larger than in the smaller 

 wound, shows a certain quantitative relation 

 to the size of the wound. 



Essentially and disregarding complicating 

 factors, the same stimulus leads to the migra- 

 tion of cells and to cell prolification in wound 

 healing.- To understand wound healing it is 

 necessary to study experimentally the condi- 

 tions which influence the migration of the 

 cells into the wound. The important fact in 

 wound healing is that in a tissue which was 

 previously at rest, the making of a defect 

 calls forth new activities in the cells adjoin- 

 ing the wound. 



2. In earlier investigations we have shown 

 that after the shedding of the blood of 

 Limulus the amoebocytes agglutinate and thus 

 produce a tissue-like organization which under 

 certain experimental conditions bears a cer- 

 tain resemblance to epithelial, under others to 

 connective tissue. This agglutination of cells 

 is not accompanied by a transformation of 

 fibrinogen into fibrin.^ Subsequently we ob- 

 served that an emigration of cells takes place 

 from such tissue if pieces of this " cellfibrin " 

 are put on a slide and kept under suitable 

 conditions.* 



"We have recently resumed these experi- 

 ments and have succeeded in working out 

 methods which permit us within certain 

 limits to imitate in an experimental tissue 

 composed of agglutinated blood cells processes 

 which are characteristic of normal tissues. 



2 A more detailed discussion of these conditions 

 will be given in a forthcoming paper on wound 

 healing in the Journal of Medical Besearch. 



3 Leo Loeb, Biological Bulletin, 1903, IV., 301 ; 

 Vircliow's AroMv, 1908, Vol. 173, 35. 



<i Leo Loeb, Biochem. Zeitsehrift, 1909, XVI., 

 157. 



3. In such experimental " cellfibrin " tissue 

 the processes of wound healing and tissue 

 grafting can be imitated, as far as the pri- 

 mary process in wound healing, namely the 

 formation of layers of regenerating tissue 

 through migration, is concerned. A defect in 

 this artificial tissue, measuring about 6-8 

 square mm. can be closed in the course of two 

 to three days, and a piece of tissue grafted 

 into a defect can be seen to unite with the 

 host tissue through regeneration taking place 

 in the host as well as in the graft. We have 

 every reason to believe that the essential 

 factors underlying these healing processes in 

 the skin of a mammal and in such experi- 

 mental cellfibrin tissue are very similar. In 

 both cases a tissue which has been in a rest- 

 ing condition is made to migrate into a 

 wound under the influence of the wound 

 stimulus. 



4. In order to produce cellfibrin tissue, we 

 collect in a stender dish a certain quantity of 

 blood of a large Limulus under conditions 

 which preserve the blood cells as much as 

 possible. The latter form several layers on 

 the bottom of the dish. The cells are glued to 

 each other as well as to the bottom of the 

 dish and thus form a compact even layer of 

 tissue. With a scalpel we can make wounds 

 of various sizes in this tissue and then readily 

 follow with a low power of the microscope 

 the diilerent stages of wound healing. At the 

 border of the wotmd we may recognize the 

 outgrowth of the regenerated tissue even with 

 the naked eye. In this defect we can trans- 

 plant tissue of the same kind and follow the 

 union between host and graft. 



We may furthermore cut out a very small 

 piece of tissue, place it on a cover glass, add 

 a drop of blood serum or other fluid, and fix 

 it with vaselin on a hollow slide, in the same 

 way as in the case of other tissues growing in 

 vitro. We can thus follow the radial out- 

 growth of the tissue. The pictiires obtained 

 correspond closely to those seen in the vitro 

 culture of other tissues. 



5. We have begun an analysis of the con- 

 ditions determining wound healing in this 



