Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (5): 2050-2059.doi: 10.4103/NRR.NRR-D-22-00311

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Induced pluripotent stem cell–derived mesenchymal stem cells enhance acellular nerve allografts to promote peripheral nerve regeneration by facilitating angiogenesis

Fan-Qi Meng1, 2, 3, 4, #, Chao-Chao Li2, 3, 5, #, Wen-Jing Xu2 , Jun-Hao Deng2, 5, 6, Yan-Jun Guan2, 3, 5, Tie-Yuan Zhang2, 3, 5, Bo-Yao Yang2, 3, 5, Jian Zhang2, 3, 5, Xiang-Ling Li2, 3, 5, Feng Han2, 3, 5, Zhi-Qi Ren2, 3, 5, Shuai Xu1 , Yan Liang1 , Wen Jiang7, 8, Jiang Peng2, 3, 5, *, Yu Wang2, 3, 5, *, Hai-Ying Liu1, *   

  1. 1 Department of Spine Surgery, Peking University People’s Hospital, Beijing, China;  2 Beijing Key Lab of Regenerative Medicine in Orthopedics, Institute of Orthopedics, Chinese PLA General Hospital, Beijing, China;  3 Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China;  4 Department of Anesthesiology, Capital Medical University Xuanwu Hospital, Beijing, China;  5 Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, China;  6 Department of Orthopedics, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region, China;  7 National Clinical Research Center for Orthopedics, Beijing, China;  8 Department of Pain Treatment, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, China
  • Online:2026-05-15 Published:2025-08-23
  • Contact: Jiang Peng, PhD, pengjiang301@126.com; Yu Wang, PhD, wangwangdian628@126.com; Hai-Ying Liu, PhD, liuhaiying_pku@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 32171356 (to YW); Self-Support Research Projects of Shihezi University, No. ZZZC2021105 (to WJ), Capital Medical University Natural Science Cultivation Fund, No. PYZ23044 (to FQM), Beijing Municipal Natural Science Foundation, No.7244410 (to JHD).

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Abstract: Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells. However, adult tissue–derived mesenchymal stem cells encounter various obstacles, including limited tissue sources, invasive acquisition methods, cellular heterogeneity, purification challenges, cellular senescence, and diminished pluripotency and proliferation over successive passages. In this study, we used induced pluripotent stem cell-derived mesenchymal stem cells, known for their self-renewal capacity, multilineage differentiation potential, and immunomodulatory characteristics. We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury. Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation. Furthermore, the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats. Additionally, our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization. Collectively, our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats, offering promising therapeutic strategies for clinical translation.

Key words: acellular nerve allograft, angiogenesis, bioluminescence imaging, conditioned medium, induced pluripotent stem cell–derived mesenchymal stem cells, micro-CT scanning, Microfil perfusion, peripheral nerve injury