Abstract 20865: Experience From the First-in-Human Case--A Phase I Clinical Trial Evaluating the Safety of Allogeneic Adipose Tissue-Derived Multilineage Progenitor Cells-Transplantation Therapy in Severe Familial Hypercholesterolemia Patients
Introduction: Familial hypercholesterolemia (FH) is an inherited disorder, mainly caused by defects in low-density lipoprotein (LDL) receptor gene. Although most of heterozygous FH patients are able to be treated with statin, ezetimibe, bile acid sequestrants and anti-PCSK9 antibody, homozygous FH patients are resistant to drug therapy.
Hypothesis: With the increase of the evidence about the safety of mesenchymal stem cells and percutaneous transhepatic portal approach in islet transplantation, we hypothesized that cell-transplantation therapy with allogeneic adipose tissue-derived multilineage progenitor cells, could be an alternative treatment instead of liver transplantation for severe FH patients.
Methods and Results: We have first performed a couple of pre-clinical studies. 1) Adipose tissue were harvested from healthy donor and multi-lineage progenitor cells (ADMPCs) were isolated. ADMPCs were able to differentiate into hepatocyte-like cells by appropriate growth factor stimulation, which expressed albumin and incorporated DiI-labeled LDL particles. 2) Xenogenic ADMPCs were transplanted into WHHL rabbits, an animal model of FH, via portal vein (3x107 cells / rabbit). Serum total cholesterol levels were reduced significantly within four weeks and maintained to the end of study. 3) Pravastatin were administrated into WHHL rabbits after ADMPCs transplantation. Administration of statin enhanced the effect of ADMPCs transplantation by up-regulation of LDL-receptor activity and resulted in significant additional reduction in total cholesterol. Based on these evidences, we generated a protocol for the first-in-human clinical trial. Briefly, 1). 50-100 ml of subcutaneous adipose-tissue are harvested from the donor under local anesthesia. 2). ADMPCs are isolated and cultured for 3-4 weeks. 3). Allogeneic ADMPCs (1.0 x 107/kg) are transplanted into FH patients via portal vein under local anesthesia. Here, we have transplanted allogeneic 4.8 x 108 ADMPCs into a 54 y.o. female FH patient on Feb, 2016 and the patient are currently under observation.
Conclusion: We have experienced the first-in-human case of allogeneic ADMPCs transplantation in a severe FH patient.
Author Disclosures: M. Koseki: None. A. Saga: None. T. Okada: None. K. Kanno: None. K. Tomita: None. K. Osuga: None. S. Ezoe: None. M. Nishida: None. Y. Sakata: None. S. Yamashita: None.
- © 2016 by American Heart Association, Inc.