Journal
SURGERY TODAY
Volume 51, Issue 4, Pages 634-650Publisher
SPRINGER
DOI: 10.1007/s00595-020-02117-0
Keywords
Muse cells; Mesenchymal stem cells; Swine hepatectomy model; Allogeneic cell administration
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Funding
- Program for Basic and Clinical Research on Hepatitis of the Japan Agency for Medical Research and Development (AMED) [JP17fk0210303]
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The study demonstrates that allogeneic Muse cell administration via the portal vein can effectively improve liver dysfunction in a swine model of PHLF, with significant reparative effects.
Introduction Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic endogenous pluripotent-like cells residing in the bone marrow that exert a tissue reparative effect by replacing damaged/apoptotic cells through spontaneous differentiation into tissue-constituent cells. Post-hepatectomy liver failure (PHLF) is a potentially fatal complication. The main purpose of this study was to evaluate the safety and efficiency of allogeneic Muse cell administration via the portal vein in a swine model of PHLF. Methods Swine Muse cells, collected from swine bone marrow-mesenchymal stem cells (MSCs) as SSEA-3(+) cells, were examined for their characteristics. Then, 1 x 10(7)allogeneic-Muse cells and allogeneic-MSCs and vehicle were injected via the portal vein in a 70% hepatectomy swine model. Results Swine Muse cells exhibited characteristics comparable to previously reported human Muse cells. Compared to the MSC and vehicle groups, the Muse group showed specific homing of the administered cells into the liver, resulting in improvements in the control of hyperbilirubinemia (P = 0.04), prothrombin international normalized ratio (P = 0.05), and suppression of focal necrosis (P = 0.04). Integrated Muse cells differentiated spontaneously into hepatocyte marker-positive cells. Conclusions Allogeneic Muse cell administration may provide a reparative effect and functional recovery in a 70% hepatectomy swine model and thus may contribute to the treatment of PHLF.
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