Ann Anat. 2023 Jul 15:152131. doi: 10.1016/j.aanat.2023.152131. Online ahead of print.
ABSTRACT
BACKGROUND: Functional hematopoiesis is governed by the bone marrow (BM) niche, which is compromised by radiotherapy, leading to radiation-induced BM failure. The aim of this study was to demonstrate the radiation induced pathological remodeling of the niche and the efficacy of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in restoring hematopoiesis via improvement of the niche.
METHODS: Thirty male Wistar rats were equally assigned to three groups: control (CON), irradiated (IR), and IR + hUCB-MSCs. Biochemical, histopathological and immunohistochemical analyses were performed to detect collagen type III and IV, Aquaporin 1+ sinusoidal endothelial cells and immature hematopoietic cells, CD11c+ dendritic cells, Iba1+ macrophages, CD9+ megakaryocytes, Sca-1+, cKit+, CD133 and N-cadherin+ hematopoietic stem and progenitor cells, CD20+, Gr1+ mature hematopoietic cells, in addition to ki67+ proliferation, Bcl-2+ anti-apoptotic, caspase-3+ apoptotic, TNF-α+ inflammatory cells. Histoplanimetry data were statistically analyzed using the one-way analysis of variance followed by the post hoc Duncan’s test. Moreover, Pearson’s correlation was used to assess the correlation between variables parameters.
RESULTS: In comparison to the IR group, the IR+hUCB-MSCs group showed restored cell populations and extracellular collagen components of the BM niche with significant increase in hematopoietic stem, progenitor, mature and proliferating cells, and a considerable decrease in apoptotic and inflammatory cells. Furthermore, highly significant correlations between BM niche and blood biochemical, histopathological, and immunohistochemical parameters were observed.
CONCLUSION: hUCB-MSCs restored functional hematopoiesis through amelioration of the BM niche components via reduction of oxidative stress, DNA damage, inflammation, and apoptosis with upregulation of cellular proliferation.
PMID:37460043 | DOI:10.1016/j.aanat.2023.152131
