Umbilical Cord Mesenchymal Stem Cells Induce Differentiation Of Retinoic Acid-Resistant Promyelocytic Leukemia Cells

AIM:Mesenchymal stem cells (MSCs) have capacity of differentiate into multiple cell types and self-renew. Recently, Mesenchymal stem cell research in the therapy of tumor diseases through the secretion of anti-cancer molecular, such as interferon, interleukin, and apoptosis inducer. Retinoic acid resistant promyelocytic leukemia cells (NB4-R2) show a defect in RA signaling and express both mutated form and wild form of PML-RAR alpha receptors.METHODS:(1)Combining UC-MSCs and all trans-retinoic coculture with NB4-R2 cells to analysis cells differentiation;(2)Using Cell Counting Kit-8 (CCK 8) analysis of UC-MSC on NB4-R2 proliferation;(3) Analysis of NB4-R2 cells cycle by apoptosis Kit;(4)Real-time PCR verification of differentially expressed PML-RAR alpha receptors, C/EBP β, C/EBP ε genes;(5)Western blotting test PML-RARalpha protein level.CONCLUSION:Combining UC-MSC and ATRA can degrade the PML-RAR alpha receptors and induce granulocyte differentiation. As well as UC-MSC can inhibit NB4-R2 proliferation through arrest the cell cycle at G0/G1.Background:Mesenchymal stem cells (MSCs) are not only multipotent, but also could mediate immunomodulation. Recently, groups of clinical studies report that MSCs reveal notable therapeutic effects on diabetes, GVHD, and autoimmune diseases. Safety of MSCs is crucial for MSCs clinical application, and one of them is to test whether or not MSCs could promote tumor growth in vivo; however, fewer studies has been reported on this field.Aim:We use human breast cancer cells MCF-7 tumor-burdened mice as model, to observe the influence of the mesenchymal stem cells and tumor growth in vivo.Method:In this study, we gave three different doses (4×104,2×105 and 1 × 106/per mice) of umbilical cord derived MSCs (UC-MSCs) twice to MCF-7 tumor-burdened BALB/c nude mice via intravenous injection during six weeks. Healthy nude mice and MCF-7 tumor-burdened mice without transplantation were served as control. Tumor size and weight were measured in the end.Result:Our results indicated a trend that UC-MSCs could inhibit tumor growth (p>0.05) and histological analysis showed that in each of high and middle dose-group, there was one mouse had lung metastases.