Pediatr Surg Int. 2019 Sep 24. doi: 10.1007/s00383-019-04564-4. [Epub ahead of print]

Therapeutic potential of spheroids of stem cells from human exfoliated deciduous teeth for chronic liver fibrosis and hemophilia A.

Takahashi Y¹, Yuniartha R¹, Yamaza T², Sonoda S³, Yamaza H⁴, Kirino K¹, Yoshimaru K¹, Matsuura T¹, Taguchi T¹.

Abstract

PURPOSE:

Mesenchymal stem cell (MSC)-based cell therapies have emerged as a promising treatment option for various diseases. Due to the superior survival and higher differentiation efficiency, three-dimensional spheroid culture systems have been an important topic of MSC research. Stem cells from human exfoliated deciduous teeth (SHED) have been considered an ideal source of MSCs for regenerative medicine. Thus, in the present study, we introduce our newly developed method for fabricating SHED-based micro-hepatic tissues, and demonstrate the therapeutic effects of SHED-based micro-hepatic tissues in mouse disease models.

METHODS:

SHED-converted hepatocyte-like cells (SHED-HLCs) were used for fabricating spherical micro-hepatic tissues. The SHED-HLC-based spheroids were then transplanted both into the liver of mice with CCl₄-induced chronic liver fibrosis and the kidney of factor VIII (F8)-knock-out mice. At 4 weeks after transplantation, the therapeutic efficacy was investigated.

RESULTS:

Intrahepatic transplantation of SHED-HLC-spheroids improved the liver dysfunction in association with anti-fibrosis effects in CCl₄-treated mice. Transplanted SHED-converted cells were successfully engrafted in the recipient liver. Meanwhile, renal capsular transplantation of the SHED-HLC-spheroids significantly extended the bleeding time in F8-knock-out mice.

CONCLUSIONS:

These findings suggest that SHED-HLC-based micro-hepatic tissues might be a promising source for treating pediatric refractory diseases, including chronic liver fibrosis and hemophilia A.