Abstract
Calf Spleen Extractive Injection (CSEI), extracted from the spleen of healthy cows (within 24 hours of birth), is a small-peptide-enriched extraction and often used as an ancillary agent in cancer therapy. This study evaluated the hematopoietic function of CSEI and its underlying mechanisms, principally in CHRF, K562 cells, BMNCs and a mouse model of cyclophosphamide (CTX)-induced hematopoietic suppression. CSEI promoted the proliferation and differentiation of CHRF and K562 cells, activated hematopoietic- and proliferation-related factors RSK1p90, ELK1 and c-Myc, and facilitated the expression of differentiation- and maturation-related transcription factors GATA-1, GATA-2. In the mice with hematopoietic suppression, 3 weeks of CSEI administration enhanced the bodyweights and thymus indices, suppressed the spleen indices and strongly elevated the production of HSPCs, neutrophils and B cells in bone marrow, ameliorated bone marrow cellularity, and regulated the ratio of peripheral blood cells. Proteome profiling combined with ELISA revealed that CSEI regulated the levels of cytokines, especially G-CSF and its related factors, in the spleen and plasma. Additional data revealed that CSEI promoted phosphorylation of STAT3, which was stimulated by G-CSF in both mice spleen and cultured BMNCs. Taken together, CSEI has the potential to improve hematopoietic function via the G-CSF-mediated JAK2/STAT3 signaling pathway.
Highlights
The hematopoietic system, comprising the entire system of blood production, is composed of hematopoietic cells and organs, the latter including the bone marrow, lymph nodes, thymus, spleen and liver[1]
K562 cells, which resemble human erythroid and megakaryocytic progenitors, have been widely used in a human hematopoietic cell model to study the differentiation of erythrocytes and megakaryocytes[18,19,20]; CHRF cells resemble human megakaryoblasts
The proportion of benzidine-positive cells after 24 h of Calf spleen extractive injection (CSEI) incubation increased to 6.3% from 1.6% (P < 0.01; Fig. 1b), whereas the expression of erythrocyte antigen glycophorin A in K562 cells was increased to 9.5% from 3.4% (Fig. 1c)
Summary
The hematopoietic system, comprising the entire system of blood production, is composed of hematopoietic cells and organs, the latter including the bone marrow, lymph nodes, thymus, spleen and liver[1]. Bone marrow is the main source of hematopoietic progenitors and is where red blood cells, granulocytes, megakaryocytes, lymphocytes and monocytes are generated[2]. Granulocyte colony-stimulating factor (G-CSF) has been used clinically as an auxiliary chemotherapeutic agent due to its functionality in reducing chemotherapy-induced infections in cases of nonlymphoid www.nature.com/scientificreports/. CSEI has significantly increased the generation of red blood cells, hemoglobin and platelets in patients with cancer anemia[16, 17]. To further address the multifunctional activities of CSEI in hematopoiesis, we analyzed its effects on the proliferation and differentiation on hematopoietic cells in K562 and CHRF cells and measured its protective activities in a mouse model of CTX-induced hematopoietic injury and in cultured bone marrow mononuclear cells (BMNCs). Combining the in vitro and in vivo data, possible mechanisms involving G-CSF-mediated Janus kinase 2 (JAK2) /STAT3 signaling were further explored
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