衰老相关的镰状细胞病小鼠骨髓间充质基质细胞的形态功能变化

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

机构信息

Blood Center of Ribeirão Preto - Ribeirão Preto Medical School, University of São Paulo, 2501 Tenente Catão Roxo Avenue, 14051-060, Ribeirão Preto, São Paulo, Brazil.

Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Department of Hematology and Cell Therapy, Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, 01246-000, Brazil.

出版信息

Hematol Oncol Stem Cell Ther. 2024 Mar 22;17(2):120-129. doi: 10.56875/2589-0646.1115.

DOI:10.56875/2589-0646.1115

PMID:38560971

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.

摘要

背景与目的

骨髓间充质基质细胞（BM-MSCs）是造血龛的关键组成部分，参与造血干细胞（HSCs）的调节机制。血液系统疾病可影响 MSCs 及其功能。然而，镰状细胞病（SCD）引起的失调尚未完全阐明。本研究使用镰状细胞小鼠（Townes-SS）探索了 BM-MSCs 的变化及其与年龄的关系。

材料与方法

从 Townes-SS 以及 30 日龄和 60 日龄的 Townes-AA 和 C57BL/6 J 对照组中分离 BM-MSCs。

结果

BM-MSCs 在培养中无形态学差异，并表现出类似鼠 MSC 的免疫表型特征（Sca-1+，CD29+，CD44+，CD90.2+，CD31-，CD45-，和 CD117-）。随后，所有 BM-MSCs 均能在体外分化为脂肪细胞和成骨细胞。最后，30 日龄的 Townes-SS BM-MSCs 中与 HSCs 维持相关的基因表达较高（Cxcl12、Vegfa 和 Angpt1），而促炎基因（Tnfa 和 Il-6）的表达较低。然而，60 日龄的 Townes-SS BM-MSCs 开始表现出与 HSC 维持减少相关的基因表达增加和促炎基因表达增加。