The evaluation of the safety and efficacy of intravenously administered allogeneic multilineage-differentiating stress-enduring cells in a swine hepatectomy model

Masahiro Iseki, Masamichi Mizuma, Shohei Wakao, Yoshihiro Kushida, Katsuyoshi Kudo, Masahiko Fukase, Masaharu Ishida, Tomoyuki Ono, Mitsuhiro Shimura, Ichiro Ise, Yukie Suzuki, Teruko Sueta, Ryuta Asada, Shinobu Shimizu, Yoshiyuki Ueno, Mari Dezawa, Michiaki Unno

研究成果: Article査読

抄録

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 × 107 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.

本文言語English
ページ(範囲)634-650
ページ数17
ジャーナルSurgery today
51
4
DOI
出版ステータスPublished - 2021 4
外部発表はい

ASJC Scopus subject areas

  • 外科

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