Transplantation of human adipose tissue-derived multilineage progenitor cells reduces serum cholesterol in hyperlipidemic watanabe rabbits

Hanayuki Okura, Ayami Saga, Yuichi Fumimoto, Mayumi Soeda, Mariko Moriyama, Hiroyuki Moriyama, Koji Nagai, Chun Man Lee, Shizuya Yamashita, Akihiro Ichinose, Takao Hayakawa, Akifumi Matsuyama

Research output: Contribution to journalArticle

16 Citations (Scopus)

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. 125I-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.

Original languageEnglish
Pages (from-to)145-154
Number of pages10
JournalTissue Engineering - Part C: Methods
Volume17
Issue number2
DOIs
Publication statusPublished - 01-02-2011

Fingerprint

Cholesterol
Lipoproteins
Adipose Tissue
Stem Cells
Transplantation
Tissue
Rabbits
Serum
Hyperlipoproteinemia Type II
LDL Lipoproteins
alpha 1-Antitrypsin
Factor IX
LDL Receptors
Immunosuppressive Agents
Human engineering
Bile Acids and Salts
Liver
Albumins
Animals
Pumps

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering

Cite this

Okura, Hanayuki ; Saga, Ayami ; Fumimoto, Yuichi ; Soeda, Mayumi ; Moriyama, Mariko ; Moriyama, Hiroyuki ; Nagai, Koji ; Lee, Chun Man ; Yamashita, Shizuya ; Ichinose, Akihiro ; Hayakawa, Takao ; Matsuyama, Akifumi. / Transplantation of human adipose tissue-derived multilineage progenitor cells reduces serum cholesterol in hyperlipidemic watanabe rabbits. In: Tissue Engineering - Part C: Methods. 2011 ; Vol. 17, No. 2. pp. 145-154.
@article{6432b5113ab444259e7ad0b48818a865,
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. 125I-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.",
author = "Hanayuki Okura and Ayami Saga and Yuichi Fumimoto and Mayumi Soeda and Mariko Moriyama and Hiroyuki Moriyama and Koji Nagai and Lee, {Chun Man} and Shizuya Yamashita and Akihiro Ichinose and Takao Hayakawa and Akifumi Matsuyama",
year = "2011",
month = "2",
day = "1",
doi = "10.1089/ten.tec.2010.0139",
language = "English",
volume = "17",
pages = "145--154",
journal = "Tissue Engineering - Part C: Methods",
issn = "1937-3384",
publisher = "Mary Ann Liebert Inc.",
number = "2",

}

Okura, H, Saga, A, Fumimoto, Y, Soeda, M, Moriyama, M, Moriyama, H, Nagai, K, Lee, CM, Yamashita, S, Ichinose, A, Hayakawa, T & Matsuyama, A 2011, 'Transplantation of human adipose tissue-derived multilineage progenitor cells reduces serum cholesterol in hyperlipidemic watanabe rabbits', Tissue Engineering - Part C: Methods, vol. 17, no. 2, pp. 145-154. https://doi.org/10.1089/ten.tec.2010.0139

Transplantation of human adipose tissue-derived multilineage progenitor cells reduces serum cholesterol in hyperlipidemic watanabe rabbits. / Okura, Hanayuki; Saga, Ayami; Fumimoto, Yuichi; Soeda, Mayumi; Moriyama, Mariko; Moriyama, Hiroyuki; Nagai, Koji; Lee, Chun Man; Yamashita, Shizuya; Ichinose, Akihiro; Hayakawa, Takao; Matsuyama, Akifumi.

In: Tissue Engineering - Part C: Methods, Vol. 17, No. 2, 01.02.2011, p. 145-154.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Transplantation of human adipose tissue-derived multilineage progenitor cells reduces serum cholesterol in hyperlipidemic watanabe rabbits

AU - Okura, Hanayuki

AU - Saga, Ayami

AU - Fumimoto, Yuichi

AU - Soeda, Mayumi

AU - Moriyama, Mariko

AU - Moriyama, Hiroyuki

AU - Nagai, Koji

AU - Lee, Chun Man

AU - Yamashita, Shizuya

AU - Ichinose, Akihiro

AU - Hayakawa, Takao

AU - Matsuyama, Akifumi

PY - 2011/2/1

Y1 - 2011/2/1

N2 - 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. 125I-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.

AB - 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. 125I-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.

UR - http://www.scopus.com/inward/record.url?scp=79551516124&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551516124&partnerID=8YFLogxK

U2 - 10.1089/ten.tec.2010.0139

DO - 10.1089/ten.tec.2010.0139

M3 - Article

C2 - 20698754

AN - SCOPUS:79551516124

VL - 17

SP - 145

EP - 154

JO - Tissue Engineering - Part C: Methods

JF - Tissue Engineering - Part C: Methods

SN - 1937-3384

IS - 2

ER -