Age-related Morphofunctional Changes in Sickle Cell Mice Bone Marrow Mesenchymal Stromal Cells.

Hematology/oncology and stem cell therapy Pub Date : 2024-03-22 DOI:10.56875/2589-0646.1115

Felipe A Rós, Péricles N M da Costa, Jonathan Milhomens, Débora G L de La-Roque, Fernanda U Ferreira, Juliana de Matos Maçonetto, Camila C de Oliveira Menezes Bonaldo, Julianne V de Carvalho, Patrícia V B Palma, Wassim El Nemer, Dimas T Covas, Simone Kashima

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Abstract

Background and objectives: Bone marrow mesenchymal stromal cells (BM-MSCs) are key elements of the hematopoietic niche and participate in the regulatory mechanisms of hematopoietic stem cells (HSCs). Hematological diseases can affect MSCs and their functions. However, the dysregulations caused by sickle cell disease (SCD) are not fully elucidated. This work explored changes in BM-MSCs and their relationship with age using sickle cell mice (Townes-SS).

Materials and methods: BM-MSCs were isolated from Townes-SS, and control groups 30- and 60-day-old Townes-AA and C57BL/6 J.

Results: The BM-MSCs showed no morphological differences in culture and demonstrated a murine MSC-like immunophenotypic profile (Sca-1+, CD29+, CD44+, CD90.2+, CD31-, CD45-, and CD117-). Subsequently, all BM-MSCs were able to differentiate into adipocytes and osteocytes in vitro. Finally, 30-day-old BM-MSCs of Townes-SS showed higher expression of genes related to the maintenance of HSCs (Cxcl12, Vegfa, and Angpt1) and lower expression of pro-inflammatory genes (Tnfa and Il-6). However, 60-day-old BM-MSCs of Townes-SS started to show expression of genes related to reduced HSC maintenance and increased expression of pro-inflammatory genes.

Conclusion: These results indicates age as a modifying factor of gene expression of BM-MSCs in the context of SCD.

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镰状细胞小鼠骨髓间充质基质细胞与年龄相关的形态功能变化。

背景和目的：骨髓间充质基质细胞（BM-MSCs）是造血生态位的关键要素，参与造血干细胞（HSCs）的调节机制。血液病会影响间充质干细胞及其功能。然而，镰状细胞病（SCD）导致的失调尚未完全阐明。这项研究利用镰状细胞小鼠（Townes-SS）探讨了BM-间充质干细胞的变化及其与年龄的关系：从Townes-SS、对照组30天和60天大的Townes-AA和C57BL/6 J中分离出BM-间充质干细胞：结果：BM-间充质干细胞在培养过程中无形态学差异，并表现出类似鼠间充质干细胞的免疫表型特征（Sca-1+、CD29+、CD44+、CD90.2+、CD31-、CD45-和CD117-）。随后，所有 BM-MSCs 都能在体外分化成脂肪细胞和骨细胞。最后，30 天龄的 Townes-SS BM-MSCs 表现出较高的造血干细胞维持基因（Cxcl12、Vegfa 和 Angpt1）表达量和较低的促炎基因（Tnfa 和 Il-6）表达量。然而，60 天龄的 Townes-SS BM-MSCs 开始出现造血干细胞维持相关基因表达减少和促炎基因表达增加的现象：结论：这些结果表明，在 SCD 的情况下，年龄是改变 BM-MSCs 基因表达的一个因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Hematology/oncology and stem cell therapy

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