Multifaceted therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for acute liver failure in rats

Abstract

In acute liver failure (ALF), a poorly controlled innate immune response causes massive hepatic destruction, which elicits a systemic inflammatory response, progressive multiple organ failure and ultimate sudden death. Although the liver has inherent tissue-repairing activities, its regeneration during ALF fails, and orthotopic liver transplantation is the only curative approach. Here we show that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED-derived serum-free conditioned medium (SHED-CM) into the d-galactosamine-induced rat model of ALF markedly improved the condition of the injured liver and the animals' survival rate. The engraftment of infused SHEDs was very low, and both SHEDs and SHED-CM exerted similar levels of therapeutic effect, suggesting that the SHEDs reversed ALF by paracrine mechanisms. Importantly, SHED-CM attenuated the ALF-induced pro-inflammatory response and generated an anti-inflammatory/tissue-regenerating environment, which was accompanied by the induction of anti-inflammatory M2-like hepatic macrophages. Secretome analysis by cytokine antibody array revealed that the SHED-CM contained multiple tissue-regenerating factors with known roles in anti-apoptosis/hepatocyte protection, angiogenesis, macrophage differentiation and the proliferation/differentiation of liver progenitor cells. Taken together, our findings suggest that SHEDs produce factors that provide multifaceted therapeutic benefits for AFL. Copyright © 2015 John Wiley & Sons, Ltd.

Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications

“…10 Stem Cells International that expressed Arginase-1, Ym-1, and CD206 in vitro. These findings were further proved in vivo [124][125][126], where intravenous administration of SHED-CM in a bleomycin-induced acute lung injury mouse model, reduced lung fibrosis, and enhanced survival rates. These therapeutic effects were elicited through reducing the expression of proinflammatory cytokines and fibrotic markers such as α-smooth muscle actin, thereby reducing fibrosis by altering proinflammatory M1 into an anti-inflammatory M2 phenotype [112,113,126].…”

Stem cell‐derived conditioned media from human exfoliated deciduous teeth promote bone regeneration

“…Further, it has been demonstrated by cytokine array analyses that SHED‐CM contain numerous factors such as OPG, TIMP‐1, TIMP‐2, ANG, MCP‐1, VEGF‐A and multiple liver‐regeneration factors, which are involved in anti‐apoptosis/hepatocyte protection, angiogenesis, macrophage differentiation and the proliferation/differentiation of liver progenitor cells. Subsequently, it was found that SHED‐CM injection into a d ‐galactosamine‐induced rat model of acute liver failure markedly improves the condition of the injured liver and animal survival rates (Matsushita et al, ).…”

Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity

“…Dental pulp stem cells secrete a broad repertoire of trophic and immunomodulatory factors that have the potential to treat various types of intractable diseases [22][23][24][25][26][36][37][38][39][40][41]. We previously showed that the factors in SHED-CM improve PNI in a rat model of sciatic nerve transection; however, the mechanisms involved in repairing the damaged nerve have been elusive.…”