Transplantation of spleen cells in patients with hemophilia A

Abstract

It has been reported that coagulation factor VIII (F. VIII) is produced in the spleen and other organs. Transplantation of splenic whole organ and spleen cells may, therefore, be used to treat patients with hemophilia A. The donor spleen from brain-dead donors was used to prepare spleen cell suspension for transplantation. Twenty-two spleen cell transplantations were performed on 20 patients suffering from severe hemophilia A at our institutes. Two of them underwent a second infusion of spleen cells since there was no increase in plasma F. VIII activity after the first transplantation. All but two patients showed a marked clinical improvement. Increased plasma F. VIII activity was observed in 18 of 20 cases. The peak plasma F. VIII activity in these recipients rose to 10%-15% posttransplantation in 14 cases and to over 15% in 4 cases from pretransplant levels of 0%-3%. Generally, the elevation of plasma F. VIII activity could be detected 4-7 days following transplantation of spleen cells and this lasted from 22 to 58 weeks. Four patients whose peak plasma F. VIII activity was greater than 15% experienced an uneventful course after transplantation. The patients with plasma F. VIII activity over 10% showed less frequent bleeding and prolonged intervals between bleed as well as improvement in hemophilic arthrosis. Two patients who had interval hematuria before transplantation did not have any relapse for up to 2 years after infusion of the spleen cells. These results indicate that spleen cell transplantation may be a promising method for the management of patients with hemophilia A.

Haemophilia and the mysterious spleen: the story of a hate–love relationship

“…All showed ‘marked clinical improvement’. Liu et al [68] also infused cadaver spleen cells in 20 Haemophiliacs and saw a rise in factor VIII in 18, up to c. 10% 4–7 days after treatment; bleeding became less frequent and at longer intervals. On another tack, Hoeben et al [69] failed to observe expression in vivo of mouse factor‐VIII gene transferred by retrovirus into the marrows of irradiated mice, although 90% of spleen colonies contained the vector.…”

Transplantation of endothelial cells corrects the phenotype in hemophilia A mice

“…The liver being the major source of FVIII synthesis, normal levels of FVIII were restored following orthotopic liver transplantation in people with hemophilia A [10,11]. In contrast, transplantation of lymphatic tissue, lung or spleen was less effective [12–15]. However, identification of the liver cell type(s) responsible for FVIII synthesis and storage has been controversial.…”

Transduction of modified factor VIII gene improves lentiviral gene therapy efficacy for hemophilia A

“…Although the liver, and in particular liver sinusoidal ECs (LSECs; lymphatic endothelial and hematopoietic cells), are considered the main source of F8 biosynthesis ( 29 , 30 , 31 , 32 ). F8 syntheses in other tissues and cell types, such as the spleen and myeloid cells, have been reported ( 33 , 34 , 35 , 36 , 37 ). Recent studies have presented evidence that ECs are the main or even the only source of de novo F8 biosynthesis, and F8 activation preferentially occurs in ECs and hematopoietic cells, rather than in hepatocytes ( 38 , 39 , 40 ).…”