Proliferation and differentiation of hepatic stem cell from bone marrow cells and possibility of bone marrow transplantation in genetic hepatic disease
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Showa University|
AOKI Takeshi Showa University, Department of surgery II, Assistant professor (30317515)
加藤 博久(2003) 昭和大, 医学部, 助手 (10286784)
KUSANO Mitsuo Showa University, Department of Surgery II, Professor (70091569)
KATO Hirohisa Showa University, Department of Surgery II, Assistant professor (10286784)
SHIMIZU Yoshinori Showa University, Department of Surgery II, Assistant professor (00276552)
|Project Period (FY)
2003 – 2004
Completed(Fiscal Year 2004)
|Budget Amount *help
¥3,500,000 (Direct Cost : ¥3,500,000)
Fiscal Year 2004 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 2003 : ¥2,100,000 (Direct Cost : ¥2,100,000)
|Keywords||Bone marrow transplantation / Analbuminemic rat / Hepatocyte Growth Factor / Diabetes / Insulin producing cell / 細胞移植 / 骨髄細胞 / 肝幹細胞 / スナムセル / 肝細胞移植 / 骨髄細胞移植|
Whole liver or partial liver transplantation is the only effective method of treating end-stage liver disease in humans, but its application is limited by an insufficient number of donor organs and the high cost. Allogeneic hepatocyte transplantation has been studied as an alternative method of liver transplantation. But its use also has been limited by the limited number of donors.
Many studies in the past several years have shown that bone marrow cells can differentiate into various cell lineage in vitro and in vivo such as lipocyte, cardiac myoblast, skin epithelium, neuron, and hepatocytes lineage. Moreover, Lagasse, et. al. found that bone marrow cell transplantation into fumarylacetoacetate hydrolase (FAH)-deficient mice, an animal model of human fatal congenital tyrosinemia type rescued the mice and restored their liver function, and Li, et. Al. showed improvement of neurologic recovery in a rat stroke model with intracarotid administration of bone marrow stromal cell. These s
tudies demonstrated that bone marrow cells are an ideal resource for cell transplantation therapy.
We investigated the feasibility of correcting the congenital absence of albumin in Nagase analbuminemic rats (NAR) by allogeneic bone marrow cell transplantation. Seven week-old male NARs were used as recipients, and 6- to 8- week-old male Sprague-Dawley (SD) rats were used as allograft donors. NARs were divided into three groups: a bone marrow transplantation (BMT) group (n=10) in which bone marrow cells were infused into the liver; a hepatocyte transplantation (HCT) group (n=8) in which hepatocytes were transplanted into the liver; and a control group (n=8) in which PBS was injected into the portal vein. Serum albumin levels were measured as an indicator of the function of the grafted cells, and the phenotypic characteristics of the engrafted cells in the recipient's liver were assessed with immunohistochemical and immunofluorescence techniques. At 8 weeks after cell transplantation the serum albumin levels of the BMT group and HCT group were significantly higher than in the control group. The hepatocyte-like cells derived from bone marrow cells expressed albumin in liver of the NARs. From this result, bone marrow cells can differentiate into hepatocyte-like cells in vivo. The results show that bone marrow cell transplantation is an effective treatment for congenital analbuminemia in a rat model and suggest that allogeneic bone marrow cell transplantation can be used as an efficient therapy for hereditary metabolic diseases.
Recent studies have demonstrated that the transplantation of bone marrow cells following diabetes induced by streptozotocin can support the recovery of pancreatic beta-cell mass and a partial reversal of hyperglycemia. To address this issue, we examined whether the c-Met/hepatocyte growth factor (HGP) signaling pathway was involved in the recovery of beta-cell injury after bone marrow transplantation (BMT). In this model, donor-derived bone marrow cells were positive for HGF immunoreactivity in the recipient spleen, liver, lung, and pancreas as well as in the host hepatocytes. Indeed, plasma HGF levels were maintained at a high value. The frequency of c-Met expression and its proliferative activity and differentiative response in the pancreatic ductal cells in the BMT group were greater than those in the PBS-treated group, resulting in an elevated number of endogenous insulin-producing cells. The induction of the c-Met/HGF signaling pathway following BMT promotes pancreatic regeneration in diabetic rats. Less
Research Products (5results)