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<p>Human bone marrow mesenchymal stromal/stem cells (BM-MSCs) are widely used in clinical trials and tissue engineering, yet their native microenvironment remains poorly understood. Here we introduce a tissue-clearing protocol, DeepBone, for human bones and integrate it with simultaneous mRNA and protein detection. Using this protocol, we spatially map BM-MSCs relative to key bone microenvironment components, including human blood capillaries, adipocytes, sinusoids and bony trabeculae. Quantitative analysis reveals that the native microenvironment of human BM-MSCs in young bone is enriched in vasculature, sinusoids, bone matrix and adipocytes. In contrast, in aged bone, BM-MSCs show no preferential association with bone or adipocytes. Proliferative BM-MSCs are predominantly found along blood vessels. Moreover, we identify a specialized microenvironment for BM-MSCs in young bone, characterized by sinusoids coiled around trabeculae and enriched by R-type vessels. These findings provide insights into the native niches of BM-MSCs, offering a foundation for the development of tissue engineering strategies that mimic their physiological context.</p>

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Three-dimensional quantitative tissue clearing reveals differences in osteovascular niche of aged and young human mesenchymal stromal cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月17日

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  • Nelson Tsz Long Chu,
  • Ostap Dregval,
  • Yu-Wei Chang,
  • Emil Kriukov,
  • Xin Tian,
  • Xin Liu,
  • Dana Trompet,
  • Misty Shuo Zhang,
  • Lei Li,
  • Zhong Li,
  • Emiliano Gomez Ruiz,
  • Joana B. Pereira,
  • Mats Brittberg,
  • Björn Barenius,
  • Lars Sävendahl,
  • Ralf H. Adams,
  • Inger Gjertsson,
  • Claes Ohlsson,
  • Giovanni Volpe,
  • Andrei S. Chagin

摘要

Human bone marrow mesenchymal stromal/stem cells (BM-MSCs) are widely used in clinical trials and tissue engineering, yet their native microenvironment remains poorly understood. Here we introduce a tissue-clearing protocol, DeepBone, for human bones and integrate it with simultaneous mRNA and protein detection. Using this protocol, we spatially map BM-MSCs relative to key bone microenvironment components, including human blood capillaries, adipocytes, sinusoids and bony trabeculae. Quantitative analysis reveals that the native microenvironment of human BM-MSCs in young bone is enriched in vasculature, sinusoids, bone matrix and adipocytes. In contrast, in aged bone, BM-MSCs show no preferential association with bone or adipocytes. Proliferative BM-MSCs are predominantly found along blood vessels. Moreover, we identify a specialized microenvironment for BM-MSCs in young bone, characterized by sinusoids coiled around trabeculae and enriched by R-type vessels. These findings provide insights into the native niches of BM-MSCs, offering a foundation for the development of tissue engineering strategies that mimic their physiological context.