Dissecting the hematopoietic microenvironment. V: limitations of repair following damage to the hematopoietic support stroma.

Damage and repair of the hematopoietic microenvironment of the spleen was studied using X-irradiation, anoxic necrosis induced by splenic ligation, or a combination of the two, as the destructive agents. Spleen colony number, size and type, 59Fe uptake, and microscopic study of splenic structure were used as means of assessment. The most severe or least repaired damage was induced by high dose irradiation (4000 r), by 1000 r followed immediately by splenic ligation, and by two successive splenic ligations separated by a 30 day recovery period. It was seen that reduction of CFUs lodgment, as measured by f factor, played a very major role in the lesser number of spleen colonies formed after either kind of damage. Following the several treatments, the numbers of spleen colonies formed, their size and their typing as erythrocytic or granulocytic varied independently of each other, suggesting that these functions of the microenvironment, and the cell types responsible for them, are independent of each other. The exhaustion of regenerative capacity displayed by repeatedly ligated spleens suggested a maximal limit for stromal cell replications commensurate with Hayflick's hypothesis.