Effects of human umbilical cord-derived mesenchymal stem cells on hematologic malignancies

Abstract

Mesenchymal stem cells (MSCs) have been used in hematopoietic stem cell transplantation for years. However, the safety of MSCs applied in various types of hematologic malignancy has not been comprehensively explored. In the present study, the effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on six representative hematologic malignancy cell lines were explored, including leukemia, multiple myeloma and lymphoma cells. Direct and indirect co-culture models were established, and cell proliferation was assessed by carboxyfluorescein diacetate succinimidyl ester staining. A cytometric bead array cytokine kit was used to quantify cytokines. The expression of interleukin (IL)-6 receptor elements on tumor cells was detected by reverse transcription-polymerase chain reaction and flow cytometry, and the effects of exogenous IL-6 on cell proliferation were determined using a Cell Counting kit-8 assay. The results demonstrated that hUC-MSCs inhibited the proliferation of most of the cell lines examined (THP-1, HL-60, K562 and RPMI-8226), but promoted the proliferation of Raji cells. In addition, hUC-MSCs secreted abundant IL-6, promoted the secretion of IL-10 by RPMI-8226 and Raji cells, and inhibited the secretion of tumor necrosis factor-α by THP-1 cells. These data indicate a varied effect of hUC-MSCs on various types of hematologic malignancy, including distinct mechanisms of cell-to-cell contact and cytokines. Researchers applying hUC-MSCs in lymphoma should be aware of a potential tumor growth-promoting effect.

Expression and role of fibroblast activation protein α in acute myeloid leukemia

“…The interaction between AML cells and BMMSCs, either via direct contact or secreted cytokines, can promote AML progression, survival, growth, chemotherapy resistance and angiogenesis (43)(44)(45)(46). However, little is known regarding the function of FAPα expression in BMMSCs and how it affects the features of AML cells.…”

“…Previous studies have revealed that, via a variety of mechanisms, BMMSCs inhibit AML cell apoptosis and promote their survival, proliferation and chemotherapy resistance (46)(47)(48)(49)(50)(51). In addition, it has been reported that Wnt ligands are the key drivers of most types of tissue stem cells in adult mammals, and mutated Wnt pathway components are causative in the progression of multiple growth-related pathologies and cancer (52).…”

What is the impact of human umbilical cord mesenchymal stem cell transplantation on clinical treatment?

“…HUC-MSCs can exert an anti-tumor effect also by affecting transcriptional regulation in leukemia cells. Additionally, HUC-MSCs can enhance the proliferation and migration of cancer cells [ 102 , 103 ]. So far, there is no conclusive proof of HUC-MSC tumorigenicity or their ability to promote the development of cancer already present in the organism.…”

Mesenchymal stem cells in acute myeloid leukemia: a focus on mechanisms involved and therapeutic concepts

“…In another investigation, Li et al (2018) showed that UC-MSCs inhibited the proliferation of HL-60 and THP-1 cells as AML cell lines. Their results indicate varying effects of UC-MSCs on various types of AML cell lines associated with secreted cytokines and the expression of cytokine receptors on the cells [35]. They suggested different mechanisms, such as secretion of certain substances or paracrine signals, for the antitumor effects of UC-MSCs, besides cell cycle arrest, but the exact mechanism was not determined in their study.…”

“…In addition, antibodies specific for CD123 are under evaluation [67]. Li et al (2018) indicated that the anti-CD44 antibody A3D8 inhibits proliferation of HL-60 cells, a representative acute leukemia cell line [35]. The A3D8 treatment increased the percentage of cells in G0/G1 cell cycle phase [68].…”