The Involvement of Macrophage Colony Stimulating Factor on Protein Hydrolysate Injection Mediated Hematopoietic Function Improvement

Abstract

Protein hydrolysate injection (PH) is a sterile solution of hydrolyzed protein and sorbitol that contains 17 amino acids and has a molecular mass of 185.0–622.0 g/mol. This study investigated the effect of PH on hematopoietic function in K562 cells and mice with cyclophosphamide (CTX)-induced hematopoietic dysfunction. In these myelosuppressed mice, PH increased the number of hematopoietic cells in the bone marrow (BM) and regulated the concentration of several factors related to hematopoietic function. PH restored peripheral blood cell concentrations and increased the numbers of hematopoietic stem cells and progenitor cells (HSPCs), B lymphocytes, macrophages, and granulocytes in the BM of CTX-treated mice. Moreover, PH regulated the concentrations of macrophage colony stimulating factor (M-CSF), interleukin (IL)-2, and other hematopoiesis-related cytokines in the serum, spleen, femoral condyle, and sternum. In K562 cells, the PH-induced upregulation of hematopoiesis-related proteins was inhibited by transfection with M-CSF siRNA. Therefore, PH might benefit the BM hematopoietic system via the regulation of M-CSF expression, suggesting a potential role for PH in the treatment of hematopoietic dysfunction caused by cancer therapy.

Macrophage colony-stimulating factor and its role in the tumor microenvironment: novel therapeutic avenues and mechanistic insights

“…Secondly, M-CSF modulates TAM cytokine secretion, including IL-2, VEGF, EGF, TGF-b, and CCL22 (13,21,68), thereby impacting the behavior of tumor cells. These cytokines play diverse roles in tumor development, including stimulating angiogenesis, suppressing T cell-mediated immune responses, and promoting tumor cell survival and proliferation (13,23,36).…”

“…M-CSF is closely related to chemotherapy and radiotherapy. Chemotherapeutic drugs, such as cyclophosphamide (CTX), have been shown to reduce M-CSF levels in tissues, thereby inhibiting tumor cell survival (68). Furthermore, M-CSF is associated with the response to radiotherapy, as the expression of M-CSF in glioblastoma cells is related to resistance to the anti-tumor drug 5-FU (38).…”

“…Since cancer treatments may lead to bone marrow suppression and immune function decline, the use of M-CSF can promote the proliferation and differentiation of hematopoietic stem cells, thereby improving bone marrow function and immune function. For example, the use of hydrolyzed protein injection upregulated the expression of IL-2 and M-CSF, altering the composition of bone marrow hematopoietic cell populations, increasing the numbers of hematopoietic stem cells, B lymphocytes, macrophages, and granulocytes (68). Therefore, the use of M-CSF can alleviate the side effects during treatment and improve the quality of life for patients.…”

Impact of macrophage differentiation on hematopoietic function enhancement by Shenzhu ErKang Syrup

“…The number of hematopoietic-associated cells in the bone marrow is one of the indicators that directly evaluates the hematopoietic function of the organism [4,22]. CTX had an inhibitory effect on the myeloid population including naïve cells (Lin − ), HSCs (Lin − Sca-1 + c-Kit + ), LT-HSCs (Lin − Sca-1 + c-Kit + CD48 − CD150 + ), B lymphocytes (CD45 + CD19 + ) and macrophages (CD11b + F4/80 + ) compared with normal mice (Figure 2A-2E).…”