title: Transplantation of human adipose tissue-derived multilineage progenitor cells reduces serum cholesterol in hyperlipidemic Watanabe rabbits.
abstract: Familial hypercholesterolemia (FH) is an autosomal codominant disease characterized by high concentrations of proatherogenic lipoproteins and premature atherosclerosis secondary to low-density lipoprotein (LDL) receptor deficiency. We examined a novel cell therapy strategy for the treatment of FH in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for homozygous FH. We delivered human adipose tissue-derived multilineage progenitor cells (hADMPCs) via portal vein and followed by immunosuppressive regimen to avoid xenogenic rejection. Transplantation of hADMPCs resulted in significant reductions in total cholesterol, and the reductions were observed within 4 weeks and maintained for 12 weeks. (125)I-LDL turnover study showed that the rate of LDL clearance was significantly higher in the WHHL rabbits with transplanted hADMPCs than those without transplanted. After transplantation hADMPCs were localized in the portal triad, subsequently integrated into the hepatic parenchyma. The integrated cells expressed human albumin, human alpha-1-antitrypsin, human Factor IX, human LDL receptors, and human bile salt export pump, indicating that the transplanted hADMPCs resided, survived, and showed hepatocytic differentiation in vivo and lowered serum cholesterol in the WHHL rabbits. These results suggested that hADMPC transplantation could correct the metabolic defects and be a novel therapy for inherited liver diseases.
authors.affiliation: Department of Somatic Stem Cell Therapy and Health Policy, Foundation for Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Hanayuki
authors.initials: H
authors.lastname: Okura
authors.forename: Ayami
authors.initials: A
authors.lastname: Saga
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Fumimoto
authors.forename: Mayumi
authors.initials: M
authors.lastname: Soeda
authors.forename: Mariko
authors.initials: M
authors.lastname: Moriyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Moriyama
authors.forename: Koji
authors.initials: K
authors.lastname: Nagai
authors.forename: Chun-Man
authors.initials: CM
authors.lastname: Lee
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ichinose
authors.forename: Takao
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Akifumi
authors.initials: A
authors.lastname: Matsuyama
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D048430:Cell Shape; D002470:Cell Survival; D002784:Cholesterol / Q000097:blood*; D005260:Female; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood*; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002784:Cholesterol