Review Article

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Blood Res 2019; 54(3):

Published online September 30, 2019

https://doi.org/10.5045/br.2019.54.3.165

© The Korean Society of Hematology

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

Ezzatollah Fathi1, Zohreh Sanaat2, Raheleh Farahzadi2

1Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, 2Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Correspondence to : Raheleh Farahzadi, Ph.D.
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
E-mail: farahzadir@tbzmed.ac.ir

Received: May 16, 2019; Revised: June 19, 2019; Accepted: July 4, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

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

Article

Review Article

Blood Res 2019; 54(3): 165-174

Published online September 30, 2019 https://doi.org/10.5045/br.2019.54.3.165

Copyright © The Korean Society of Hematology.

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

Ezzatollah Fathi1, Zohreh Sanaat2, Raheleh Farahzadi2

1Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, 2Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Correspondence to:Raheleh Farahzadi, Ph.D.
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
E-mail: farahzadir@tbzmed.ac.ir

Received: May 16, 2019; Revised: June 19, 2019; Accepted: July 4, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Mesenchymal stem cells, Hematologic malignancy, Acute myeloid leukemia, Cancer therapy, Cell cycle arrest

Fig 1.

Figure 1.

Multi-lineage differentiation and cell surface markers of MSCs.

Blood Research 2019; 54: 165-174https://doi.org/10.5045/br.2019.54.3.165

Fig 2.

Figure 2.

Therapeutic implications of MSCs in the treatment of leukemia.

Blood Research 2019; 54: 165-174https://doi.org/10.5045/br.2019.54.3.165

Fig 3.

Figure 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.

Blood Research 2019; 54: 165-174https://doi.org/10.5045/br.2019.54.3.165

Fig 4.

Figure 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.

Blood Research 2019; 54: 165-174https://doi.org/10.5045/br.2019.54.3.165
Studies reporting that MSCs affect hematologic malignancy by inhibiting/promoting tumor growth.
Blood Res
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