The following hypothesis may be deduced from the evidence just submitted: The endothelium of the end capillaries, the fibroblast, and the immediate derivatives of these two are all mesenchymal in origin. Injury produces a reaction wherein there is stasis and hemorrhage, with the exudation of cells and fluids that contain some element or elements that affect these mesenchymal derivatives in such a way as to reestablish their embryonal characteristics. As a result, they form a local, temporary mesenchyma at the site of injury, proliferate, migrate, and differentiate according to the needs of the case until the injury is repaired. They may form connective tissue, phagocytes, polyblasts, new vessels, etc. Phagocytosis and absorption gradually withdraw the exciting agents from the seat of injury, the temporary mesenchyma returns to adult type, and all that remains is the products of the process that are necessary for scar formation. It is apparently erroneous to think of the mononuclear cells of young granulation tissue as fibroblasts, endotheliocytes, etc., they should be considered as representing various stages in the differentiation of a local mesenchyma until the process of healing is completed, when they return to the adult types represented by these more specific names. The term polyblast, originated by Maximow, is particularly applicable to these cells, for under the conditions they are truely polyblastic; but that they are derived from lymphocytes is not indicated by results of this experiment—the lymphocytes and plasma cells appear to play a part that is unconnected with the formation of new tissue.
No definite statement can be made as to the nature of the stimulating substance, or substances, that bring about this reversion to embryonal type. As indicated, they are associated in some way with the blood, for the most marked cellular metaplasia is noted in connection with areas of hemorrhage, or in proximity to vascular areas. That the exciting substances are contained in the erythrocytes is furthermore indicated by the fact that the most metaplastic areas are found where the mesenchymoid cells are growing among masses of red corpuscles, with little visible fluid or fibrin present (cf. Fig. 24). Whether these substances are enzymes or not is purely problematical.
There is very little, in the several hundred sections studied for this and later papers, to indicate that wound healing is an orderly procession of specific cells to designated positions in these wounds. The only tissues retaining their continuity in growth to a degree in any way comparable with the descriptions in some text-books, are the surface epithelium and the vascular buds, or branches. The majority of mononuclear cells of mesenchymal type appear to fill in the injured area by migration, rather than by growth in continuity. Once they have reached a certain point, they react in the various ways just described. There is, of course, a migration of differentiated cells, such as macrophages, polymorphonuclears, lymphocytes, etc., from the healthy tissue; but the framework, or structural foundation, of the granulation tissue appears to be composed of the practically undifferentiated derivatives of the connective tissue and capillary endothelium. In other words, it is conceivable that cells originating from connective tissue might become phagocytes and vice versa, both types temporarily losing all specificity under the influence of some chemical or enzymatic excitant in the exudate. Until we understand the physiology and chemistry that determine the developmental and retrograde changes of the normal, embryonal mesenchyma, as well as those of this temporary mesenchyma, we can never fully comprehend wound healing.