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<p>Acute ischemic stroke triggers immunosuppression, yet existing therapies struggle to balance neuroprotection with poststroke immunosuppression. We demonstrated that bone marrow mesenchymal stem cells (BM-MSC) reverse stroke-induced thymic atrophy by promoting T-cell differentiation and restoring peripheral T-cell populations. Bulk RNA sequencing of BM-MSC-treated thymuses revealed enhanced proliferative signatures. Mechanistically, BM-MSC secrete migrasomes (organelles derived from migrating cells) that traverse the blood‒thymus barrier. Single-cell RNA sequencing analysis demonstrated that migrasome-mediated proliferation occurred specifically in medullary thymic epithelial cell I (mTECI) subpopulations. Proteomic profiling via liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) identified Pin1—a cell cycle regulator—as the predominant cargo in BM-MSC-derived migrasomes. In vivo and in vitro studies confirmed migrasome-mediated thymic epithelial proliferation, T-cell niche reconstruction, and immune homeostasis restoration. Migrasome monotherapy improved neurological deficits and survival rates in stroke model mice, demonstrating dual neuroprotective-immunomodulatory efficacy. This work addresses the clinical dilemma between neuroprotection and immunosuppression alleviation, establishing migrasomes as a cell-free therapeutic strategy for poststroke immunotherapy.</p>

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BM-MSC-derived migrasomes reverse stroke-induced thymic atrophy and immunosuppression via Pin1 delivery to thymic epithelial cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月15日

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  • Haotong Yi,
  • Mengyan Hu,
  • Liling Yuan,
  • Xiaotao Su,
  • Shilin Wu,
  • Tiemei Li,
  • Shisi Wang,
  • Xinmei Kang,
  • Yuxin Liu,
  • Zhiruo Liu,
  • Qin Qin,
  • Weihua Yu,
  • Yifan Li,
  • Wei Qiu,
  • Wei Cai,
  • Zhengqi Lu

摘要

Acute ischemic stroke triggers immunosuppression, yet existing therapies struggle to balance neuroprotection with poststroke immunosuppression. We demonstrated that bone marrow mesenchymal stem cells (BM-MSC) reverse stroke-induced thymic atrophy by promoting T-cell differentiation and restoring peripheral T-cell populations. Bulk RNA sequencing of BM-MSC-treated thymuses revealed enhanced proliferative signatures. Mechanistically, BM-MSC secrete migrasomes (organelles derived from migrating cells) that traverse the blood‒thymus barrier. Single-cell RNA sequencing analysis demonstrated that migrasome-mediated proliferation occurred specifically in medullary thymic epithelial cell I (mTECI) subpopulations. Proteomic profiling via liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) identified Pin1—a cell cycle regulator—as the predominant cargo in BM-MSC-derived migrasomes. In vivo and in vitro studies confirmed migrasome-mediated thymic epithelial proliferation, T-cell niche reconstruction, and immune homeostasis restoration. Migrasome monotherapy improved neurological deficits and survival rates in stroke model mice, demonstrating dual neuroprotective-immunomodulatory efficacy. This work addresses the clinical dilemma between neuroprotection and immunosuppression alleviation, establishing migrasomes as a cell-free therapeutic strategy for poststroke immunotherapy.