Stem cell Therapy for Liver Disease

Abstract

We already reported that the mesenchymal stem cells could be isolated from human umbilical cord blood and the differentiation into muscle, nerve cell, endothelial cell and hepatocyte could be possible. And we tried clinical application after approval of Korean FDA in Buerger`s disease and liver cirrhosis and had the very promising results.

Buerger`s disease is characterized pathologically as a panangiitis of medium and small blood vessels including both arteries and adjacent veins. The vascular involvement shows a predilection for distal extremity vessels including digital, palmar and plantar, and tibioperoneal arteries. The etilology is unknown but the association with cigarette smoking is a striking characteristic. A possible allergy or hypersensitivity to a component of cigarette smoking may contribute to this disorder. Usually the symptoms start with claudication of the foot. Ischemic rest pain develops progressively and may affect not only the toes but also the fingers. Affected digits may show signs of cyanosis or dependent rubor. Gangrene and ulceration are the next step. Finally the affected limb and the aweful pain may be treated by amputation. Therapeutic angiogenesis was studied by many researchers in patients with ischemic heart and lower limbs. Angiogenesis is tightly regulated in a complex balance between pro- and anti- angiogenic mechanisms. They have tried to overcome any limitations of the natural angiogenic response by increasing substantially the local concentrations of angiogenic growth factors either by administering recombinant protein or the gene that codes for an angiogenic growth factors or by administering EPCs(Endothelial Progenitors cells) that will synthesize cocktail of growth factors in the vicinity of new vessel formation. The EPCs were harvested from peripheral blood, autologous bone marrow and human umbilical cord blood(UCB). We demonstrated that mononuclear cells obtained from human umbilical cord blood contained significant amounts of EPCs and other mesenchymal stem cell components. And in our animal model we proved that transplantation of cord blood-derived MSCs augmented neovascularization in the ischemic limb of immunodeficent nude mice. 3 men with Buerger`s disease who were already treated with medical and surgical therapies were nearly in narcotics-addicted status. They were performed with umbilical cord blood (UCB) stem cell transplantation on the affected areas, 2 upper and 1 lower extremities, with HLA typing after informed consent. The results were fantastic. 2 men showed sudden disappearance of pain sensation on their affected extremities after 2nd day of treatment. One man`s pain lasted 14 days after treatment but his pain was relieved within one month and he quitted narcotic analgesics after one month of treatment. Now they all stop analgesics and have only vasodilating drugs. The follow-up angiography showed increasing appearance of digital capillaries and decreasing vascular resistence in their extremities comparing with the preoperative study. These cases illustrate the remarkable efficacy of the UCB stem cell transplantation on Buerger`s didease. Thus we propose that therapeutic angiogenesis of UCB stem cell transplantation is an effective means for tissue salvage in patients with critical limb ischemia.

Liver transplantation is the accepted method of treatment for end stage liver disease. Development of various immunosuppressive drugs and advances in the surgical techniques have led to the improvement in patient and graft survival. The number of donor for liver transplantation, however, is in shortage seriously in contrast to growing numbers of patients. Such gap between liver- donor and recipient becomes the major limitation of liver replacement therapy. So we need to find an alternative, effective and safe therapeutic method to treat liver cirrhosis. The use of human hepatocytes in the management of various liver based metabolic conditions and acute and chronic liver failure suggested us some possibility . The understanding of the process of self-renewal and differentiation of the stem cell has both changed and progressed over the last few decades. For many years, the assumption was that the liver regenerates primarily through the division of mature liver cells. However, over the last few years there has been increasing evidence of the participation of stem cells. In addition, extrahepatic stem cells may migrate from the bone marrow into the liver when the regenerative capacity of the liver itself is depleted. It is not yet fully clear how the different stem cell populations interact with both each other and the mature liver cell population to achieve homeostatic cell and differentiation equilibrium in the diseased and/or regenerating organ. In any case, the outstanding growth potential of liver stem cells may become a clinically viable option in the field of cell transplantation. Here we report the early results of Umbilical Cord Blood Stem Cell Transplantation for Liver cirrhosis. The general conditions and the laboratory data of the patients changed very positively. And CT volumetry of the treated cirrhotic liver gave us possibility of the cure as we already had the good results of angiography in Buerger`s disease. Transplantation of UCB stem cell for liver cirrhosis is not curative treatment modality at present but seems to be the curative one in the near future by the basic research of the stem cell and some modification of the purification and culture methods and some development of route of administration of the UCB stem cell.