Regenerative medicine using dental pulp stem cells for liver diseases

Abstract

Acute liver failure is a refractory disease and its prognosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells (MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes. A point worthy of special mention is that dental pulp can be obtained from deciduous teeth during childhood and can be subsequently harvested when necessary after deposition in a tooth bank. MSCs have not only a regenerative capacity but also act in an anti-inflammatory manner via paracrine mechanisms. Promising efficacies and difficulties with the use of MSC derived from teeth are summarized in this review.

Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review

“…14,15,53 The most promising clinical applications for this stem cell source involve the correction of metabolic diseases and the treatment of liver diseases with high mortality rates, such as cirrhosis and hepatocellular carcinoma. 54,55 Over time, DP-MSCs have become the preferred alternative to harvesting stem cells during hepatic transplantation. 15 DP-MSCs have also been used in the field of bone regeneration.…”

Stem Cells from Cryopreserved Human Dental Pulp Tissues Sequentially Differentiate into Definitive Endoderm and Hepatocyte-Like Cells in vitro

“…hDPSCs readily differentiated into mesenchymal-lineage cells (osteocytes, chondrocytes, and adipocytes) and endodermal-lineage cells (hepatocytes and pancreatic cells), as well as neuro-ectodermal cells 6 , 14 , 16 , 17 , 20 , 21 , 22 . In addition, hDPSCs displayed remarkable functional hepatogenic differentiation potential in vitro and regeneration of injured liver tissues in vivo 2 , 6 , 18 - 22 .…”

“…Several therapeutic strategies for various liver diseases and hepatotoxicity have been explored recently 1 , 2 . One strategy involves the use of stem cells as the source of differentiated hepatocytes.…”

“…However, drawbacks of ESCs and iPSCs for clinical application in humans include ethical problems, difficulty in isolation and cultivation of autologous cells, and economic demerits. MSCs have been the focus as an alternative cell therapy source because of their multipotency, self-renewal, and multi-lineage differentiation potential 1 , 2 . MSCs from bone marrow and umbilical cord blood were the first to be successfully differentiated into hepatocyte lineage 3 .…”

“…MSCs from bone marrow and umbilical cord blood were the first to be successfully differentiated into hepatocyte lineage 3 . Subsequently, MSCs derived from various adult tissues, including fat, dental pulp and Wharton's jelly, have been broadly studied for their in vitro hepatocyte differentiation capacity and use as in vivo therapeutic agents for liver diseases 2 , 4 , 6 - 10 .…”