Efficacy of Invitro Expanded Bone Marrow Derived Allogeneic Mesenchymal Stem Cell Transplantation Via Portal Vein or Hepatic Artery or Peripheral Vein in Patients With Wilson Cirrhosis
Condition: Wilson's Disease
MeSH terms: Hepatolenticular Degeneration
Study type: Interventional

Summary: 
      Wilson's disease is an autosomal recessive genetically inherited disorder of copper
      metabolism, causing neurological, psychiatric and liver disease. The ATP7B gene on the 13th
      chromosome is responsible for the disease. Liver has a critical role on copper metabolism. It
      is the main site of copper accumulation and bile secretion is the only physiologic way of
      copper elimination. Due to defective production of ceruloplasmin which carries copper, wide
      amount of free copper precipitates throughout the body but particularly in the liver, eyes
      and brain. Patients are bound to lifelong chelating agents such as penicillamine, trientine
      and tetramine dihydrochloride. Unfortunately, these medications may cause severe side-effects
      such as hypersensitivity reactions, bone marrow suppression, auto-immune disease and
      sideroblastic anemia. Medical treatment of liver cirrhosis, the last stage of the illness
      that leads to morbidity and mortality in the Wilson Disease, is difficult. Liver
      transplantation is still the most effective treatment for the patients with liver cirrhosis
      in Wilson Disease. However, serious problems are accompanied with liver transplantation. Lack
      of liver donors, complications during and after the surgery, graft rejection and high costs
      are the main problems.

      There are cells in the human body that are capable to renew themselves and differentiate to a
      diverse range of specialized cell types. These are called "stem cells". Stem cells can be
      differentiated to specialized cells in appropriate medias in the laboratory. Recently, the
      differentiation potential of mesenchymal stem cells into hepatocytes is proved by
      demonstrating hepatocytes containing Y chromosome in the female who has had bone marrow
      transplantation from male donors. In many laboratory studies, it is observed that human bone
      marrow derived mesenchymal stem cells, transplanted to animals with induced liver damage,
      differentiate into the albumin producing hepatocytes without fusion. By these studies, it is
      understood that mesenchymal stem cells are more potent than other bone marrow elements in
      context of differentiation to hepatocytes. Even though the number of studies on human for the
      same purpose is few, findings are supporting those of animal experiments. Mesenchymal stem
      cells are non-immunogenic. Safety and feasibility of allogeneic transplantations between
      individuals without need of immunosuppressive drug regimen are proven. Proofs of correcting
      metabolic defects by this way are also presented in some publications. For the reasons
      mentioned above, allogeneic mesenchymal stem cell transplantation is a promising treatment
      modality especially for the hereditary metabolic diseases. By this way, non-immunogeneic
      mesenchymal stem cells which have healthy genetic structure, can manufacture the required
      enzyme, will be repopulated in the damaged tissue and contribute to the clinical improvement.

      In this study, mesenchymal stem cells will be derived from healthy volunteer donor's bone
      marrow and be expanded in-vitro, and then 1 million cells per kg will be infused to patients
      with liver cirrhosis related to Wilson disease, 50 million cells via hepatic artery and the
      remaining cells via peripheral vein. It is aimed to enable liver regeneration, decrease
      fibrosis rate, improve patient's health conditions, increase ceruloplasmin synthesis,
      ameliorate disorder of copper metabolism, decrease the need for chelating agents, increase
      living standards of patients, and prolong waiting time for liver transplantation. Finally it
      is aimed to establish a new and regenerative treatment protocol alternative to liver
      transplantation. For observation of clinical and laboratory improvement, patients are planned
      to be monitored by histopathologic examination of liver biopsies before and at 6th month
      after the treatment, monthly biochemical and hematologic blood tests and periodic radiologic
      examinations. This is a hopeful, avant garde and sophisticated study which may constitute new
      horizons in context of cellular therapies.
    


Intervention name(s): allogeneic mesenchymal stem cell transplantation
Intervention type(s): Genetic
Intervention description(s): 1.000.000(one million) cells/kg, IV (1/2 of dose in the Peripheral vein and 1/2 of dose into the right hepatic artery)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Transplantation,Stem Cell; Wilson's Disease