Efficacy and safety of Bio 3D conduits composed of human umbilical cord–derived mesenchymal stromal cells: A proof-of-concept study in a canine ulnar nerve defect model
Peripheral nerve injuries involving nerve defects remain challenging to treat. Although autologous nerve grafting is considered the gold standard, it has notable limitations, including donor site morbidity. To address this, we developed a scaffold-free Bio 3D conduit composed of human umbilical cord...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2025-08-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/09636897251361711 |
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| author | Kazuaki Fujita Ryosuke Ikeguchi Tomoki Aoyama Takashi Noguchi Koichi Yoshimoto Daichi Sakamoto Terunobu Iwai Tetsuya Miyamoto Yudai Miyazaki Shizuka Akieda Tokiko Nagamura-Inoue Fumitaka Nagamura Koichi Nakayama Shuichi Matsuda |
| author_facet | Kazuaki Fujita Ryosuke Ikeguchi Tomoki Aoyama Takashi Noguchi Koichi Yoshimoto Daichi Sakamoto Terunobu Iwai Tetsuya Miyamoto Yudai Miyazaki Shizuka Akieda Tokiko Nagamura-Inoue Fumitaka Nagamura Koichi Nakayama Shuichi Matsuda |
| author_sort | Kazuaki Fujita |
| collection | DOAJ |
| description | Peripheral nerve injuries involving nerve defects remain challenging to treat. Although autologous nerve grafting is considered the gold standard, it has notable limitations, including donor site morbidity. To address this, we developed a scaffold-free Bio 3D conduit composed of human umbilical cord–derived mesenchymal stromal cells (UC-MSCs) using bioprinting technology. In this study, we evaluated its efficacy and safety in a canine ulnar nerve defect model. At 10 weeks postoperatively, the Bio 3D group showed better motor and sensory recovery compared with the allograft group, as demonstrated by the pinprick test, electrophysiological studies, and hypothenar muscle wet weight (0.978 ± 0.100 vs. 0.637 ± 0.151, n = 3). Morphometric analysis revealed greater axonal regeneration, including larger myelinated axon diameters (4.27 ± 0.342 µm vs. 3.69 ± 0.161 µm, n = 3) and thicker myelin sheaths (0.621 ± 0.088 µm vs. 0.497 ± 0.021 µm, n = 3). Immunostaining showed that the number of transplanted UC-MSCs diminished over time, likely after exerting their therapeutic effects. No adverse events, systemic abnormalities, or distant human cell migration was observed. These findings suggest that UC-MSC–derived Bio 3D conduits are a promising alternative for peripheral nerve regeneration, especially for patients wishing to avoid donor nerve harvesting. |
| format | Article |
| id | doaj-art-59907bc93ac54a6fac378dedde86a6e3 |
| institution | Kabale University |
| issn | 1555-3892 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj-art-59907bc93ac54a6fac378dedde86a6e32025-08-20T03:43:14ZengSAGE PublishingCell Transplantation1555-38922025-08-013410.1177/09636897251361711Efficacy and safety of Bio 3D conduits composed of human umbilical cord–derived mesenchymal stromal cells: A proof-of-concept study in a canine ulnar nerve defect modelKazuaki Fujita0Ryosuke Ikeguchi1Tomoki Aoyama2Takashi Noguchi3Koichi Yoshimoto4Daichi Sakamoto5Terunobu Iwai6Tetsuya Miyamoto7Yudai Miyazaki8Shizuka Akieda9Tokiko Nagamura-Inoue10Fumitaka Nagamura11Koichi Nakayama12Shuichi Matsuda13Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Rehabilitation Medicine, Graduate School of Medicine, Kyoto University, Kyoto, JapanHuman Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanCyfuse Biomedical K.K., Tokyo, JapanCyfuse Biomedical K.K., Tokyo, JapanDepartment of Cell Processing and Transfusion, IMSUT CORD, The Institute of Medical Science, The University of Tokyo, Tokyo, JapanDivision of Advanced Medicine Promotion, The Advanced Clinical Center, The Institute of Medical Science, The University of Tokyo, Tokyo, JapanDepartment of Regenerative Medicine and Biomedical Engineering, Faculty of Medicine, Saga University, Saga, JapanDepartment of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanPeripheral nerve injuries involving nerve defects remain challenging to treat. Although autologous nerve grafting is considered the gold standard, it has notable limitations, including donor site morbidity. To address this, we developed a scaffold-free Bio 3D conduit composed of human umbilical cord–derived mesenchymal stromal cells (UC-MSCs) using bioprinting technology. In this study, we evaluated its efficacy and safety in a canine ulnar nerve defect model. At 10 weeks postoperatively, the Bio 3D group showed better motor and sensory recovery compared with the allograft group, as demonstrated by the pinprick test, electrophysiological studies, and hypothenar muscle wet weight (0.978 ± 0.100 vs. 0.637 ± 0.151, n = 3). Morphometric analysis revealed greater axonal regeneration, including larger myelinated axon diameters (4.27 ± 0.342 µm vs. 3.69 ± 0.161 µm, n = 3) and thicker myelin sheaths (0.621 ± 0.088 µm vs. 0.497 ± 0.021 µm, n = 3). Immunostaining showed that the number of transplanted UC-MSCs diminished over time, likely after exerting their therapeutic effects. No adverse events, systemic abnormalities, or distant human cell migration was observed. These findings suggest that UC-MSC–derived Bio 3D conduits are a promising alternative for peripheral nerve regeneration, especially for patients wishing to avoid donor nerve harvesting.https://doi.org/10.1177/09636897251361711 |
| spellingShingle | Kazuaki Fujita Ryosuke Ikeguchi Tomoki Aoyama Takashi Noguchi Koichi Yoshimoto Daichi Sakamoto Terunobu Iwai Tetsuya Miyamoto Yudai Miyazaki Shizuka Akieda Tokiko Nagamura-Inoue Fumitaka Nagamura Koichi Nakayama Shuichi Matsuda Efficacy and safety of Bio 3D conduits composed of human umbilical cord–derived mesenchymal stromal cells: A proof-of-concept study in a canine ulnar nerve defect model Cell Transplantation |
| title | Efficacy and safety of Bio 3D conduits composed of human umbilical cord–derived mesenchymal stromal cells: A proof-of-concept study in a canine ulnar nerve defect model |
| title_full | Efficacy and safety of Bio 3D conduits composed of human umbilical cord–derived mesenchymal stromal cells: A proof-of-concept study in a canine ulnar nerve defect model |
| title_fullStr | Efficacy and safety of Bio 3D conduits composed of human umbilical cord–derived mesenchymal stromal cells: A proof-of-concept study in a canine ulnar nerve defect model |
| title_full_unstemmed | Efficacy and safety of Bio 3D conduits composed of human umbilical cord–derived mesenchymal stromal cells: A proof-of-concept study in a canine ulnar nerve defect model |
| title_short | Efficacy and safety of Bio 3D conduits composed of human umbilical cord–derived mesenchymal stromal cells: A proof-of-concept study in a canine ulnar nerve defect model |
| title_sort | efficacy and safety of bio 3d conduits composed of human umbilical cord derived mesenchymal stromal cells a proof of concept study in a canine ulnar nerve defect model |
| url | https://doi.org/10.1177/09636897251361711 |
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