The In Vivo Differentiation of Human Leukoeytes into Histiocytes , Fibroblasts and Fat Cells in Subcutaneous

By Nic.uioi s L. PETRAKIS, M iu DAVIS A D SALVATORE P. Lucia O NE OF the important controversies ( f morphologic hematology concerns the concept that some of the nc’igranular mononuclear Ieukocytes of the circulating blood have the potential for further differentiation toward connective tissue and he natopoietic cells. A relationship between leukocytes of the blood and connective tissue was suggested by Cohnheim’ in 1876, who observed leukocyte diapedesis and siigges ed that the cells of the blood give rise to inflammatory exudates and, possibly, to connective tissue. Morphologic studies of leukocytes participating in inflamm:itory reactions and of leukocytes growing in tissue culture suggested to Maximow, Bloom and to others234’5 that the nongranulated leukocytes of adult blood have latent mesenchymal potentialities, which under the proper circumstances, can differentiate toward IIL1( rophages, fibroblasts, and other components cf connective tissue. However, Gther investigations of inflammatory exudates and of healing wounds, particularlv those of Marchand,#{176} and of Herzog,7 did not support this view, hut demonstrated that the leukocytes were phagocytes acting mainly as scavengers, which subsequently disintegrated. This latter view is essentially that held by most investigators today. In a recent review of wound healing, Edwards and Duinphy5 conclude, “As yet there is no concluisive evidence for a specific ( i.e. blood borne ) cell progenitor of the fibroblast.” The historical aspects of this subject have been extensively reviewed by Bloom,5 Allgower,#{176}, Rehuck and Crowley,1 FIorey11 and Trowell.12 An important factor which has obscured the possible role of the mononuclear leukocytes in the formation of connective tissue cells has been the great difficulty in following the fate of the individual leukocytes among the fibroblasts which rapidly proliferate from edges of the healing wound. The present studies were undertaken to reinvestigate the developmental potentialities of the nongranular mononuclear leukocvtes of the blood which had been cultivated subcutaneously in Algire diffusion chambers.15 The chambers were constructed with Millipore membranes which permit the diffusion of nutrients into the chamber, but do not allow the entry or exit of !eukocvtes. In this fashion, the chamber acts as a type of in vivo tissue culture