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Adipose Tissue-Derived Endothelial Like Cells for Treatment of Pulmonary Hypertension in Rats

Masaharu Kataoka

N. Nagaya

H. Yoshino

Toru Satoh


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Conference: 2010 International PHA Conference and Scientific Sessions

Release Date: 06.24.2010

Presentation Type: Abstracts

Kataoka M1, Nagaya N2, Yoshino H1, Satoh T1.
1. Department of Medicine, Division of Cardiology, Kyorin University School of Medicine, Tokyo, Japan
2. Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka, Japan

BACKGROUND: Adipose stromal cells can differentiate into multiple cell lineages. Adrenomedullin (AM) and vascular endothelial growth factor (VEGF) induce angiogenesis. We examined the therapeutic potential of adipose stromal cell-derived endothelial like cells (ELCs) for the treatment of pulmonary hypertension.

METHODS AND RESULTS: Adipose stromal cells were obtained from abdominal subcutaneous adipose tissue in rats and cultured for three weeks. Adipose stromal cells expressed endothelial lineage markers during culture with AM or VEGF. A combination of both growth factors additionally enhanced endothelial differentiation of adipose stromal cells. The cells cultured with AM and VEGF, which were defined as ELCs, showed potent angiogenic properties compared with adipose stromal cells in Matrigel assay. Although adipose stromal cells readily differentiated into adipocytes under stimulation of adipogenesis, ELCs did not differentiate into adipocytes under the same conditions. In vivo, ELCs were transplanted intravenously three days after monocrotaline injection. Transplanted ELCs were incorporated into the pulmonary vasculature and participated in vascular formation. Consequently, ELCs increased pulmonary capillary density which was decreased in monocrotaline rats. Pulmonary hypertension and survival in monocrotaline rats were significantly improved after transplantation.

CONCLUSIONSAM and VEGF additionally enhanced endothelial differentiation of adipose stromal cells. Transplantation of ELCs contributed to endothelial regeneration and improved monocrotaline-induced pulmonary hypertension. Thus, adipose tissue-derived ELCs may be a new therapeutic tool for the treatment of pulmonary hypertension.