Splenic Homotransplantation*

Abstract

During the past 12 months, five clinical whole-organ splenic homotransplantations have been carried out with the objective of providing active immunologic tissue for the recipient patients. In one case with hypogammaglobulinemia, it was hoped that the transplanted tissue would alleviate a state of immunologic deficiency. In the other four, all of whom had terminal malignancies, the purpose was to superimpose a state of altered immunologic reactivity upon the host in the hope of thereby suppressing the inexorable growth of the neoplasms.As will be described, these procedures can now be judged in each instance to have been without benefit. Nevertheless, full documentation of the cases seems justified not only because of the many implications of transplantation of immunologically competent tissue, but also because of the potentially important observations made during the care of these patients.In addition, a full account will be presented of the supporting canine studies of splenic homotransplantation, inasmuch as many of the principles of clinical therapy and investigation derived from prior observations in the dog. The fact that it is possible to obtain viable splenic homografts in the dog for as long as two-thirds of a year without the production of runt disease or other harmful effects may have application in future research on bone marrow, other lymphoid, or hepatic homografts. Canine Splenic HomotransplantationAll splenic transplants were performed with a method shown in FIGURES 1 and 2. Donors were selected of approximately the same size as the recipient, cooled to 30-32°C., and systemically heparinized (2 mg./kg.). The spleens were revascularized from the pelvic vessels (FIGURE 2) after rotating the organs end-for-end and reversing the anteroposterior relationships (FIGURE 2). By doing this, the eccentrically placed hilum was brought into convenient relation to the blood supply, allowing the long inferior pole to lie comfortably in the left paravertebral gutter without fixation. Physiologically, the preparation differs from normal in that the splenic venous drainage is into systemic rather than portal channels. For controls, autografts were performed.The protocol for splenic homotransplantation is depicted schematically in FIGURE 3.Briefly, experiments were done in which untreated hosts (FIGURE 3A), hosts pretreated with irradiation (FIGURE 3B), and hosts treated with azathioprine (FIGURE 3C) were used. Splenic autograftsSeven dogs received autografts using essentially the same technique and were either sacrificed at nine days (three animals) or followed from eight to ten and one-half months (four animals). Transfusions were not employed in any case. The average hematocrit in the three animals sacrificed after nine days dropped from 46 per cent to 32 per cent. Red cell survival studies were performed on these three dogs, each animal serving as its own control. Before surgery, 10 ml. of autogenous blood was drawn from a foreleg vein, mixed with 4 ml. of ACD solution containing five microcuries of Cr...

Correction of hemophilia as a proof of concept for treatment of monogenic diseases by fetal spleen transplantation

“…The role of the liver in factor VIII synthesis has been supported by liver transplantation studies in both hemophilic animals and humans, after which increasing factor VIII levels were detected (6)(7)(8)(9)(10). Early transplantation studies in the canine model (11,12) led, in the early 1960s, to the first human spleen transplants in four patients with malignancies and one with agammaglobulinemia (13).…”

Histopathology of spleen allograft rejection in miniature swine

“…In the few human SpTx studies, the histological picture of rejection remains uncertain (Marchioro et al . 1964; Hathaway et al .…”

“…2003). However, in large animals and in humans, its tolerogenic capacity has not been demonstrated (Marchioro et al . 1964; Booster et al .…”