Efficacy of Auxiliary Partial Orthotopic Liver Transplantation for Cure of Hemophilia in a Canine Hemophilia a Model

Ko, Saiho; Tanaka, Ichiro; Kanokogi, Hideki; Kanehiro, Hiromichi; Okayama, Junji; Ori, Jun-ichi; Shima, Midori; Yoshioka, Akira; Giles, Alan R.; Nakajima, Yoshiyuki

doi:10.1016/j.transproceed.2005.01.003

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…In veterinary medicine, transplantation therapy remains in its infancy. However, the research for transplantation techniques in dogs is available in the literature as canine liver transplantations serve as an experimental model for human liver transplantation therapy …”

Section: Therapymentioning

confidence: 99%

Acute liver failure in dogs and cats

Weingarten

Sande

2015

J Vet Emergen Crit Care

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Section: Therapymentioning

confidence: 99%

Acute liver failure in dogs and cats

Weingarten

Sande

2015

J Vet Emergen Crit Care

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“…Hepatocytes and liver sinusoidal endothelial cells, but not Kupffer cells, produce factor VIII in the mouse liver (5). 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).…”

mentioning

confidence: 99%

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

Aronovich

Tchorsh

Katchman

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Previous clinical attempts to correct genetic deficiencies such as hemophilia or Gaucher disease by transplantation of allogeneic spleen were associated with aggressive graft versus host disease, mediated by mature T cells derived from the donor spleen. We show that a fetal pig spleen harvested at the embryonic day 42 stage, before the appearance of T cells, exhibited optimal growth potential upon transplantation into SCID mice, and the growing tissue expressed factor VIII. Transplantation of embryonic day 42 spleen tissue into hemophilic SCID mice led to complete alleviation of hemophilia within 2–3 months after transplant, as demonstrated by tail bleeding and by assays for factor VIII blood levels. These results provide a proof of principle to the concept that transplantation of a fetal spleen, obtained from a developmental stage before the appearance of T cells, could provide a novel treatment modality for genetic deficiencies of an enzyme or a factor that can be replaced by the growing spleen tissue.

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“…Early transplant studies in these dogs showed that liver transplantation could correct the bleeder phenotype but that transplant of spleen or kidney did not have consistent or lasting positive effects . Beagles can also suffer from hemophilia A and have been used to show the efficacy of auxiliary partial orthotopic liver transplantation to treat hemophilia A . With the identification of the liver as the major source of FVIII, efforts focused on which cells in this organ were responsible for FVIII production.…”

Section: Fviii Is Produced By Lsecsmentioning

confidence: 99%

Progress and challenges in the development of a cell‐based therapy for hemophilia A

Fomin

Togarrati

Muench

2014

Journal of Thrombosis and Haemostasis

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Hemophilia A results from an insufficiency of factor VIII (FVIII). Although replacement therapy with plasma-derived or recombinant FVIII is a life-saving therapy for hemophilia A patients, such therapy is a life-long treatment rather than a cure for the disease. In this review we discuss the possibilities, progress and challenges that remain in the development of a cell-based cure for hemophilia A. The success of cell therapy depends on the type and availability of donor cells, the age of the host and method of transplantation, and the levels of engraftment and production of FVIII by the graft. Early therapy, possibly even prenatal transplantation, may yield the highest levels of engraftment by avoiding immunological rejection of the graft. Potential cell sources of FVIII include a specialized subset of endothelial cells known as liver sinusoidal endothelial cells (LSECs) present in the adult and fetal liver, or patient-specific endothelial cells derived from induced pluripotent stem cells (iPSCs) that have undergone gene editing to produce FVIII. Achieving sufficient engraftment of transplanted LSECs is one of the obstacles to successful cell therapy for hemophilia A. We discuss recent results from transplants performed in animals that show production of functional and clinically relevant levels of FVIII obtained from donor LSECs. Hence, the possibility of treating hemophilia A can be envisioned through persistent production of FVIII from transplanted donor cells derived from a number of potential cell sources or through creation of donor endothelial cells from patient-specific iPSCs.

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Efficacy of Auxiliary Partial Orthotopic Liver Transplantation for Cure of Hemophilia in a Canine Hemophilia a Model

Cited by 5 publications

References 16 publications

Acute liver failure in dogs and cats

Acute liver failure in dogs and cats

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

Progress and challenges in the development of a cell‐based therapy for hemophilia A

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