Transplantation of human adipose tissue-derived multilineage progenitor cells reduces serum cholesterol in hyperlipidemic Watanabe rabbits.
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.
Okura
Hanayuki
H
Department of Somatic Stem Cell Therapy and Health Policy, Foundation for Biomedical Research and Innovation, Kobe, Japan.
Saga
Ayami
A
Fumimoto
Yuichi
Y
Soeda
Mayumi
M
Moriyama
Mariko
M
Moriyama
Hiroyuki
H
Nagai
Koji
K
Lee
Chun-Man
CM
Yamashita
Shizuya
S
Ichinose
Akihiro
A
Hayakawa
Takao
T
Matsuyama
Akifumi
A
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
D015415:Biomarkers; D002784:Cholesterol