Blood Res.  2019 Sep;54(3):165-174. 10.5045/br.2019.54.3.165.

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

• Fathi E
• Sanaat Z
• Farahzadi

• KMID: 2459381
• DOI: http://doi.org/10.5045/br.2019.54.3.165

Abstract

Drug resistance in cancer, especially in leukemia, creates a dilemma in treatment planning. Consequently, studies related to the mechanisms underlying drug resistance, the molecular pathways involved in this phenomenon, and alternate therapies have attracted the attention of researchers. Among a variety of therapeutic modalities, mesenchymal stem cells (MSCs) are of special interest due to their potential clinical use. Therapies involving MSCs are showing increasing promise in cancer treatment and anticancer drug screening applications; however, results have been inconclusive, possibly due to the heterogeneity of MSC populations. Most recently, the effect of MSCs on different types of cancer, such as hematologic malignancies, their mechanisms, sources of MSCs, and its advantages and disadvantages have been discussed. There are many proposed mechanisms describing the effects of MSCs in hematologic malignancies; however, the most commonly-accepted mechanism is that MSCs induce tumor cell cycle arrest. This review explains the anti-tumorigenic effects of MSCs through the suppression of tumor cell proliferation in hematological malignancies, especially in acute myeloid leukemia.

Keyword

Mesenchymal stem cells; Hematologic malignancy; Acute myeloid leukemia; Cancer therapy; Cell cycle arrest

MeSH Terms

Cell Cycle Checkpoints
Cell Proliferation
Drug Evaluation, Preclinical
Drug Resistance
Hematologic Neoplasms
Leukemia
Leukemia, Myeloid, Acute*
Mesenchymal Stromal Cells*
Population Characteristics

Figure

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  Fig. 1 Multi-lineage differentiation and cell surface markers of MSCs.

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  Fig. 2 Therapeutic implications of MSCs in the treatment of leukemia.

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  Fig. 3 Schema for the dual roles of MSCs in hematologic malignancy. MSCs have both anti-tumorigenic and pro-tumorigenic effects, as they tend to not only inhibit tumor growth but also promote tumor growth by suppressing tumor cell apoptosis.

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  Fig. 4 MSC and tumor cell interactions as MSC-based cancer therapy. The chemotactic movement of MSCs toward a tumor niche is driven by soluble factors such as EGF, IL-6, IL-8, TGF-β, and PDGF. Genetic modification of MSCs can be used to deliver a range of tumor-suppressing cargos directly into the tumor site. These cargos include growth factors and cytokines, immune-modulating agents (IFN-α, IFN-β, IL-2, IL-12, CX3CL1 etc.), and regulators of gene expression (miRNAs and other non-coding RNAs). MSCs are also capable of delivering therapeutic drugs within the tumor site. Also, micro vesicles derived from MSCs represent an alternative approach to delivering these agents.

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