Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia

Hypercholesterolemia, Familial Clinical Trial

Official title:

In-Vitro Transdifferentiation of Mesenchymal Stem Cells to Hepatocytes and Allogenic Transplantation of Hepatocytes to the Patients With Homozygous Familial Hypercholesterolemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00515307
• Other study ID #: DDRC 85-15
• Status: Completed
• Phase: Phase 1
• First received: August 9, 2007
• Last updated: August 28, 2008
• Start date: June 2007
• Est. completion date: June 2008

Study information

• Verified date: August 2008
• Source: University of Tehran
• Contact: n/a
• Is FDA regulated: No
• Health authority: Iran: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Patients with homozygous familial hypercholesterolemia has very high serum cholesterol levels despite receiving lipid lowering drugs (e.g. statins, etc). Most of such patients die before the age of 20 due to myocardial infarction, etc. Orthotopic liver transplantation (OLT) is an effective treatment for that. Hepatocyte transplantation is an alternative to OLT that may help to overcome the shortage of donor organs. There have been reports of successful treatment of different kinds of metabolic liver disorders by hepatocyte transplantation. The major problem with hepatocyte transplantation is that the source of hepatocytes is very limited. Bone marrow stem cells are the potential source of hepatocytes. In the in-vitro culture system successful and efficient transdifferentiation of mesenchymal stem cells into hepatocytes has been documented. We have already shown that infusion of mesenchymal stem cells is safe and feasible in cirrhosis (Mohamadnejad M, et al. Arch Iran Med 2007; In Press). In this study, 2 patients with homozygous familial hypercholesterolemia will be included. The bone marrow of healthy volunteers with a normal lipid profile will be taken, then bone marrow mesenchymal stem cells (MSCs) will be cultured, and then MSCs will be trans-differentiate into hepatocytes, and the cells will be infused through the portal vein into the patients. The duration of follow up will be 6 months post-transplantation.

Description:

Patients with homozygous familial hypercholesterolemia has very high serum cholesterol levels despite receiving lipid lowering drugs (e.g. statins, etc). Most of such patients die before the age of 20 due to myocardial infarction, etc. Orthotopic liver transplantation (OLT) is an effective treatment and can decrease their serum cholesterol to near normal levels (Bilheimer DW, N Engl J Med 1984; 311:1658-64). Shortage of donor organ is a major problem for OLT. Hepatocyte transplantation is an alternative to OLT that may help to overcome the shortage of donor organ. There have been reports of successful treatment of different kinds of metabolic liver disorders (such as Crigler Najjar Syndrome (Fox IJ, et al. N Engl J Med 1998;338:1422-6), Factor VII deficiency (Dhawan A et al. Transplantation 2004:78:1812-4), Glycogen storage disease type Ia (Muraca M, et al. Lancet 2002;359:317-8), etc) by hepatocyte transplantation. The major problem with hepatocyte transplantation is that the source of hepatocytes is very limited. Bone marrow stem cells are the potential source of hepatocytes. Although, in the in-vivo system there is a controversy that if stem cells transdifferentiate into hepatocytes or fusion of stem cells and hepatocytes occur, however, in the in-vitro culture system successful and efficient transdifferentiation of mesenchymal stem cells into hepatocytes has been documented (Lee KD, et al. Hepatology 2004;40:1275-1284; & Banas A, et al. Hepatology. 2007;46:219-28). We have already shown that infusion of mesenchymal stem cells is safe and feasible in cirrhosis (Mohamadnejad M, et al. Arch Iran Med 2007; In Press). In this study, 2 female patients with homozygous familial hypercholesterolemia will be included. The bone marrow of ABO compatible healthy male volunteers with a normal lipid profile will be taken, then bone marrow mesenchymal stem cells (MSCs) will be cultured, and then MSCs will be trans-differentiate into hepatocytes in the in-vitro culture system. Then the cells will be infused through the portal vein into the patients. The duration of follow up will be 6 months post-transplantation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1
• Est. completion date: June 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Severe hypercholesterolemia unresponsive to lipid lowering agents (e.g. statins)

• Presence of tendon xanthoma

• Documentation of homozygous familial hypercholesterolemia by appropriate genetic testing

• Female gender

Exclusion Criteria:

• Male gender

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia
• Hypercholesterolemia, Familial
• Hyperlipoproteinemia Type II

Intervention

Procedure:
• Cellular transplantation
600 million to 1 billion cells will be infused through the portal vein over 30 minutes. Infusion will be done one time.

Locations

Country	Name	City	State
Iran, Islamic Republic of	Digestive Disease Research Center, Shariati Hospital, North Kargar Ave.	Tehran

Sponsors (1)

Lead Sponsor	Collaborator
University of Tehran

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum cholesterol and LDL levels		6 Months	Yes
Secondary	Tracking the infused cells		Month 2 post-transplantation	Yes