Less invasive therapies using mesenchymal stem cells (MSCs) are being developed to treat patients with severe liver cirrhosis. MSCs constitute a promising cell source for regenerative therapy and are frequently isolated from bone marrow (BMSCs) or adipose tissue (ASCs). Therefore, this study assessed the characteristics of these two cell types and their safety for cell infusion.
In vitro, exhaustive genetic analysis was performed using human (h)BMSCs and hASCs. Subsequently, the expression of messenger RNA and protein was evaluated. In vivo, mouse (m)BMSCs or mASCs was infused into serial mice via the peripheral vein, and 24-hour survival rate, prothrombin time and cause of death were analyzed.
On PCR, Western blotting, ELISA and FACS, tissue factor was found to be expressed at higher levels in hASCs than in hBMSCs. Prothrombin time in mice infused with mASCs (>120 s) was markedly longer than that of untreated mice (6.5 ± 1.7 s) and that of mice infused with BMSCs (6.7 ± 0.8 s) (P < 0.001), indicating that pro-coagulation activity was potently enhanced after ASC infusion. The 24-h survival rates in the mASC- and mBMSC-infused groups were 46.4% (13/28) and 95.5% (21/22), respectively; in the former, the rate decreased with increasing number of infused mASCs. This cell number-dependent effect was not observed with mBMSCs. A histopathological analysis of mice that died immediately following mASC infusion revealed multiple thrombi in the blood vessels of the lungs.
These results indicate that BMSCs are a superior and safer cell source for regenerative therapy.