Age-related morphofunctional changes in sickle cell mice bone marrow mesenchymal stromal cells

Bone marrow mesenchymal stromal cells (BM-MSC) are key elements of the hematopoietic niche and participate in the regulatory mechanisms of hematopoietic stem cells (HSC). 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-MSC and their relationship with age using sickle cell mice (Townes-SS). BM-MSC were isolated from Townes-SS, and control groups Townes-AA and C57BL/6J at 30- and 60-day-old. The BM-MSCs showed no morphological differences in culture and demonstrated the 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, at 30-day-old the BM-MSC of Townes-SS showed higher expression of genes related to the maintenance of HSC (Cxcl12, Vegfa and Angpt1) and lower expression of pro-inflammatory genes (Tnfa and Il-6). However, at 60-day-old the BM-MSC of Townes-SS started to show expression of genes related to reduced HSC maintenance and increased expression of pro-inflammatory genes. This indicates age as a modifying factor of gene expression of BM-MSC in the context of SCD.