Dental pulp stem cell-based therapies may be beneficial in the treatment of pediatric diseases, including chronic liver fibrosis and hemophilia A.
Therapeutic potential of spheroids of stem cells from human exfoliated deciduous teeth for chronic liver fibrosis and hemophilia A.
Pediatr Surg Int. 2019 Sep 24. doi: 10.1007/s00383-019-04564-4. [Epub ahead of print]
Takahashi Y1, Yuniartha R1, Yamaza T2, Sonoda S3, Yamaza H4, Kirino K1, Yoshimaru K1, Matsuura T1, Taguchi T1.
- Department of Pediatric Surgery, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
- Division of Oral Biological Sciences, Department of Molecular Cell Biology and Oral Anatomy, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. [email protected].
- Division of Oral Biological Sciences, Department of Molecular Cell Biology and Oral Anatomy, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
- Department of Pediatric Dentistry, Division of Oral Health, Growth, and Development, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan.
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.
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.
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.
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.