Ezzatollah Fathi - Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
Seyed Alireza Mesbah-Namin - Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Ilja Vietor - Institute of Cell Biology, Medical University of Innsbruck, Biocenter, Innsbruck, Austria
Raheleh Farahzadi - Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Objective(s): Hematopoietic stem cells (HSCs) are the cells that give rise to different types of blood cells during the hematopoiesis process. Mesenchymal stromal cells (MSCs) as key elements in the bone marrow (BM) niche interact with hematopoietic progenitor cells (HPCs) by secreting cytokines, which control HPCs maintenance and fate. Here we report that BM-MSCs are capable of inducing granulocytic differentiation of the C-Kit+ HSCs via activating JAK۳/STAT۳, ERK, and PI۳K signaling pathways.  Materials and Methods: For this purpose, BM-MSCs and C-kit+ HSCs were isolated. Next, cells were divided into two groups and differentiated into granulocytes: C-kit+ HSCs alone (control group) and co-cultured C-kit+ HSCs with MSCs (experimental group). Afterward, the gene and protein expression were assessed by real-time PCR and western blotting, respectively.Results: It was found that BM-MSCs resulted in increased JAK۳/STAT۳, ERK, and PI۳K protein expression in granulocyte differentiated C-kit+ HSCs. Conclusion: It should be concluded that MSCs could affect the granulocyte differentiation of C-kit+ HSCs via increasing JAK۳/STAT۳, ERK, and PI۳K signaling pathways.

BM C-kit+ HSCs, Cell therapy, Granulocyte differentiation, Mesenchymal stem cells, Signaling pathways