431 - A comparative study on the use of various routes in administering Muse cells for treatment of bronchopulmonary dysplasia

Poster Number: 431
Publication Number: 431.430

Ryosuke Miura, Nagoya University, NAgoya, Aichi, Japan; Yoshiaki Sato, Nagoya University Hospital, Nagoya, Aichi, Japan; Atsuto Onoda, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda, Yamaguchi, Japan; Ryoko Goto, Nagoya University, Nagoya city, Aichi, Japan; Yukina Takamoto, Nagoya university, Nagoya-city, Aichi, Japan; Takahiro Kanzawa, Nagoya University, Nagoya, Aichi, Japan; Sakiko Suzuki, Nagoya University, Nagoya, Aichi, Japan; Kazuto Ueda, Nagoya University Hospital, Nagoya, Aichi, Japan; Toshihiko Suzuki, Department of Neonatology, Tokyo Women's Medical University Medical Center East, Nagoya, Aichi, Japan; Yoshiyuki Takahashi, Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Masahiro Hayakawa, Nagoya University Hospital, Nagoya, Aichi, Japan

Background: Bronchopulmonary dysplasia (BPD) is one of the most serious complications in preterm infants. There is currently no effective treatment for BPD. Therefore, the development of new therapies is of great importance. Multilineage-differentiating stress-enduring (Muse) cells are pluripotent stem cells that can differentiate into tissue-specific cells in injured tissues to repair and restore function, and are expected to have therapeutic effects in BPD.

Objective: In this study, we investigated the therapeutic effects of Muse cells administered via different routes using a hyperoxia-induced model of BPD.

Design/Methods: Neonatal rat pups were exposed to 82.5% oxygen from postnatal day 1 (P1) to postnatal day 15 (P15) to generate a BPD animal model. Muse cells (group M) or solvent fluid (group V) were injected intravenously (i.v.) or intratracheally (i.t.) on P5. Respiratory function tests were performed on P15. We counted the white blood cells in the bronchoalveolar lavage fluid (BALF) on P16, and computed the lung tissue volume density on P29. We also investigated the weight gain and survival rates in each group.

Results: The weight gain and survival rates of both M and V groups were significantly lower when the administration route was i.t. compared to i.v. For the respiratory function test, tidal volume was significantly higher in the M-i.v. group than in the V-i.v. group (p = 0.040). White blood cell count in the BALF was significantly lower in the M group than in the V group for both i.v. and i.t. administration routes (p < 0.01 for both). An improvement in lung tissue volume density was observed in the M group but not in the V group for both i.v. and i.t. administration routes (p < 0.01 for both).Conclusion(s): The results indicate that regardless of whether the route of administration was i.v. or i.t., Muse cells produced anti-inflammatory effects and ameliorated alveolar-impaired development. However, i.t. injection did not show an amelioration in respiratory function, whereas i.v. injection did. Moreover, survival rate and body weight gain in the i.t. group were worse compared to those in the M-i.v. group. These results suggest that intravenous administration is the more suitable route of administration of Muse cells.