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骨膜骨骼干细胞在损伤后可迁移至骨髓并支持造血。

Periosteal skeletal stem cells can migrate into the bone marrow and support hematopoiesis after injury.

作者信息

Marchand Tony, Akinnola Kemi E, Takeishi Shoichiro, Maryanovich Maria, Pinho Sandra, Saint-Vanne Julien, Birbrair Alexander, Lamy Thierry, Tarte Karin, Frenette Paul, Gritsman Kira

机构信息

Service d'hématologie Clinique, Centre Hospitalier Universitaire de Rennes, Rennes, France.

UMR U1236, INSERM, Université Rennes, EFS Bretagne, Equipe Labellisée Ligue Contre le Cancer, Rennes, France.

出版信息

Elife. 2025 May 22;13:RP101714. doi: 10.7554/eLife.101714.

DOI:10.7554/eLife.101714
PMID:40401637
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12097789/
Abstract

Skeletal stem cells (SSCs) have been isolated from various tissues, including periosteum and bone marrow, where they exhibit key functions in bone biology and hematopoiesis, respectively. The role of periosteal SSCs (P-SSCs) in bone regeneration and healing has been extensively studied, but their ability to contribute to the bone marrow stroma is still under debate. In the present study, we characterized a mouse whole bone transplantation model that mimics the initial bone marrow necrosis and fatty infiltration seen after injury. Using this model and a lineage tracing approach, we observed the migration of P-SSCs into the bone marrow after transplantation. Once in the bone marrow, P-SSCs are phenotypically and functionally reprogrammed into bone marrow mesenchymal stem cells (BM-MSCs) that express high levels of hematopoietic stem cell niche factors such as Cxcl12 and Kitl. In addition, using ex vivo and in vivo approaches, we found that P-SSCs are more resistant to acute stress than BM-MSCs. These results highlight the plasticity of P-SSCs and their potential role in bone marrow regeneration after bone marrow injury.

摘要

骨骼干细胞（SSCs）已从包括骨膜和骨髓在内的各种组织中分离出来，在这些组织中，它们分别在骨生物学和造血过程中发挥关键作用。骨膜来源的骨骼干细胞（P-SSCs）在骨再生和愈合中的作用已得到广泛研究，但其对骨髓基质的贡献能力仍存在争议。在本研究中，我们建立了一种小鼠全骨移植模型，该模型模拟了损伤后最初出现的骨髓坏死和脂肪浸润。利用该模型和谱系追踪方法，我们观察到移植后P-SSCs迁移至骨髓。一旦进入骨髓，P-SSCs在表型和功能上被重编程为骨髓间充质干细胞（BM-MSCs），后者表达高水平的造血干细胞龛因子，如Cxcl12和Kitl。此外，通过体外和体内实验方法，我们发现P-SSCs比BM-MSCs对急性应激更具抗性。这些结果突出了P-SSCs的可塑性及其在骨髓损伤后骨髓再生中的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/651563f57d07/elife-101714-fig6-figsupp3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/651563f57d07/elife-101714-fig6-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/b096559c8105/elife-101714-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/e3c0625d1bd1/elife-101714-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/6f96eb5255c7/elife-101714-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/835a59a23ae3/elife-101714-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/dff141371c17/elife-101714-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/25975141bfc6/elife-101714-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/68f3ccea2b00/elife-101714-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/d7fe18247190/elife-101714-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/b5d3edeb28bb/elife-101714-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/0c752120676d/elife-101714-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/db8da56241ef/elife-101714-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/6a95ce1b7b74/elife-101714-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/189c6b8fcaf3/elife-101714-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/a8c7632382ad/elife-101714-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/1cb777a2d14d/elife-101714-fig6-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32cc/12097789/651563f57d07/elife-101714-fig6-figsupp3.jpg

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