Effect of Spiperone on Mesenchymal Multipotent Stromal and Hemopoietic Stem Cells under Conditions of Pulmonary Fibrosis

Abstract

The antifibrotic properties of spiperone and its effect on stem and progenitor cells were studied on the model of reversible bleomycin-induced pulmonary fibrosis in C57Bl/6 mice. Spiperone reduced infiltration of the alveolar interstitium and alveolar ducts with inflammatory cells and prevented the growth of the connective tissue in the parenchyma of bleomycin lungs. Apart from anti-inflammatory effect, spiperone suppressed bone marrow hemopoietic cells (CD3, CD45R (B220), Ly6C, Ly6G (Gr1), CD11b (Mac1), TER-119)-, Sca-1+, c-Kit+, CD34- and progenitor hemopoietic cells (granulocyte-erythroid-macrophage-megakaryocytic and granulocyte CFU). Spiperone-induced disturbances of fi brogenesis were paralleled by restoration of endothelial cells in the lung parenchyma, reduction of the number of circulating bone marrow cells and lung mesenchymopoietic cells (mesenchymal multipotent stromal cells (CD31-, CD34-, CD45-, CD44+, CD73+, CD90+, CD106+) and progenitor fi broblast cells), and suppression of multilineage differentiation of multipotent mesenchymal stromal cells (including fi broblast-lineage cells).

Micellar Hyaluronidase and Spiperone as a Potential Treatment for Pulmonary Fibrosis

“…We have previously demonstrated the anti-inflammatory and anti-fibrotic effects of spiperone [ 23 ]. We hypothesized that co-administration of spiperone and pHD could have higher therapeutic efficacy compared to a monotherapy with each respective compound.…”

“…Increasing the effectiveness of drug treatment is an important clinical challenge in the treatment of patients with IPF. To enhance the effects of pHD, we supplemented it with a spiperone, which itself has been proven as an anti-fibrotic agent [ 23 ].…”