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

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.

Efficacy and safety of mesenchymal stem cells co-infusion in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis

“…Mesenchymal stem cells (MSCs) are a population of multipotent, non-hematopoietic stem cells with the capability to differentiate into various cell types, such as adipocytes, osteocytes, chondrocytes, and cells present in other connective tissues [ 3 , 4 ]. MSCs, which are present in adult and fetal tissues, could be cultured in vitro and transplanted [ 3 , 5 ]. The cells are mainly obtained from bone marrow (BM), adipose tissue, peripheral blood (PB), umbilical cord blood (UCB), and amniotic fluid and amnion [ 3 , 5 , 6 ].…”

“…MSCs, which are present in adult and fetal tissues, could be cultured in vitro and transplanted [ 3 , 5 ]. The cells are mainly obtained from bone marrow (BM), adipose tissue, peripheral blood (PB), umbilical cord blood (UCB), and amniotic fluid and amnion [ 3 , 5 , 6 ]. Characterized by plasticity, self-renewal, immunomodulation, and anti-inflammatory properties, MSCs are potentially considered for regeneration medicine, transplantation, and cell therapy for many diseases [ 3 , 5 , 7 ].…”

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.…”

Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy

“…The paracrine agents can be directly secreted into the extracellular space or packaged into extracellular vesicles to be spread in the tumor milieus (Rani et al, 2015). The interaction of MSCs with tumor cell cycle is the most commonly accepted process by which MSCs exert their therapeutic effects (Fathi et al, 2019). By inhibiting proliferation-related signaling pathways, such as the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), MSCs can induce cell cycle arrest and reduce cancer growth (Lu et al, 2019).…”