2. Academic Validation
  3. HBEGF/EGFR pathway activation by hUC-MSCs improves cognitive outcomes in anti-NMDAR encephalitis

HBEGF/EGFR pathway activation by hUC-MSCs improves cognitive outcomes in anti-NMDAR encephalitis

  • Mol Ther. 2025 Oct 16:S1525-0016(25)00861-5. doi: 10.1016/j.ymthe.2025.10.040.
Jingfang Lin 1,  Bingjun Zhang 2,  Huiming Xu 3,  Xinghua Zhong 1,  Xuejia Li 4,  Yanna Song 5,  Xi Wang 3,  Yu Peng 1,  Haotian Wu 3,  Haijia Chen 4,  Jiaohua Jiang 4,  Qiyi Chen 4,  Yuanyuan Wang 6,  Changyong Tang 7,  Honghao Wang 8
Affiliations

Affiliations

  • 1 Department of Neurology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province 510180, China.
  • 2 Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510630, China; Department of Neurology, Health Management Center, Zhaoqing Hospital, The Third Affiliated Hospital of Sun Yat-sen University, Zhaoqing, Guangdong Province 526000, China.
  • 3 Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510630, China.
  • 4 Guangzhou SALIAI Stem Cell Science and Technology Co., Ltd., Guangdong Saliai Stem Cell Research Institute, Guangzhou, Guangdong Province, China.
  • 5 Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510630, China; Department of Neurology, Qingdao Municipal Hospital, Qingdao, Shandong Province 266000, China.
  • 6 Department of Neurology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province 510180, China. Electronic address: yuanyuanlisia@126.com.
  • 7 Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510630, China. Electronic address: tangchy23@mail.sysu.edu.cn.
  • 8 Department of Neurology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province 510180, China. Electronic address: wang_whh@163.com.
PMID: 41108076 DOI: 10.1016/j.ymthe.2025.10.040
Abstract

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disorder that impairs cognitive function. In this study, we investigated the impact of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on cognitive recovery in anti-NMDAR encephalitis. Our findings demonstrate that heparin-binding epidermal growth factor-like growth factor (HBEGF), a key functional factor secreted by hUC-MSCs, plays a pivotal role in ameliorating cognitive dysfunction. We elucidated that the HBEGF/epidermal growth factor receptor (EGFR) signaling pathway contributes to the enhancement of cognitive function following hUC-MSC exposure. Importantly, we employed a novel exosome-based intracellular therapeutic protein delivery technology-the mMaple3-mediated protein loading and release from exosomes (MAPLEX) system-for targeted HBEGF delivery. This approach facilitated a controlled, light-induced release of HBEGF from the exosomal membrane. Collectively, these findings support the involvement of HBEGF in mediating cognitive improvement in anti-NMDAR encephalitis induced by hUC-MSCs. Additionally, the MAPLEX system emerges as an effective delivery platform for HBEGF, potentially opening new avenues for the treatment of anti-NMDAR encephalitis.

Keywords

NMDAR; NMDAR reduction; anti-N-methyl-D-aspartate receptor encephalitis; cognitive impairment; epidermal growth factor receptor; heparin-binding epidermal growth factor-like growth factor.

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