Repopulation of Bone Marrow in Mice: Number and Type of Cells Required for Post-X-Irradiation Protection

Abstract

It is now well established that the protection against lethal X-irradiation achieved by Lorenz et al. (1, 2) by implantation of bone marrow and by Jacobson et al. (3) by the implantation of spleen results from the repopulation of the hematopoietic system by the implanted cells. The type of cell responsible for this repopulation and the number of cells required for success remain unsettled. It has generally been thought that the responsible reproductive cell is the larger blast cell. Fractionation experiments by Goodman et al. (4) were consistent with this view. However, a number of investigators have suggested that a small cell, morphologically indistinguishable from the lymphocyte, is the progenitor of hemic cells. C. Harris and Burke (5) arrived at this conclusion on the basis of morphologic observations in the bone marrow of young rats. They traced the history of this hypothesis to Maximow and Naegeli in 1900. This view was held also by Brecher et al. (6), Schooley et al. (7), and Yoffey (8). P. F. Harris (9) also observed development of all cell types from lymphocytes which appeared in the bone marrow of guinea pigs postirradiation. He reviewed the evidence in the literature in support and in contradiction of this hypothesis. Our investigations on this subject began in early 1962. In the interim, a number of reports have appeared, adding to the evidence that the small lymphocyte is indeed the totipotential cell. The most recent report on this subject, by Cudkowicz et al. (10, 11), concludes that the rate of incorporation of uridyldeoxyriboside into bone marrow is a function of the number of small lymphocytes inoculated postirradiation. These authors concentrated the lymphocytes by adsorption of other cell types on glass wool columns. Our own approach has been to fractionate bone marrow cells by differential centrifugation and to test efficacy of the fractions in