Genetically engineered mesenchymal stromal cells as a new trend for treatment of severe acute graft-versus-host disease

Abstract

Mesenchymal stem cells (MSCs) are a population of non-hematopoietic and self-renewing cells characterized by the potential to differentiate into different cell subtypes. MSCs have interesting features which have attracted a lot of attention in various clinical investigations. Some basic features of MSCs are including the weak immunogenicity (absence of MHC-II and costimulatory ligands accompanied by the low expression of MHC-I) and the potential of plasticity and multi-organ homing via expressing related surface molecules. MSCs by immunomodulatory effects could also ameliorate several immune-pathological conditions like graft-versus-host diseases (GVHD). The efficacy and potency of MSCs are the main objections of MSCs therapeutic applications. It suggested that improving the MSC immunosuppressive characteristic via genetic engineering to produce therapeutic molecules consider as one of the best options for this purpose. In this review, we explain the functions, immunologic properties, and clinical applications of MSCs to discuss the beneficial application of genetically modified MSCs in GVHD.

Keywords: GVHD; gene therapy; immunotherapy; mesenchymal stem cell.

Graphical Abstract

Figure 1.

immunomodulatory effects of MSC on the components of the immune system. The cellular characteristics of MSCs are important for their therapeutic uses. MSCs apply immunomodulatory effects on central and peripheral immune compartments through producing many immunomodulatory molecules such as TGF-β, HLA-G5, IDO, and PGE2 by the effect on M2 macrophages polarization in inflammatory conditions. MSCs also modulate central immune compartments through promoting T-cells maturation, repairing damaged thymus, inducing the proliferation of natural Tregs, and stimulation of thymocytes differentiation.

Figure 2.

characteristics of MSCs and their functional principle. MSCs have been isolated from different tissues. They exhibit a high self-renewal capacity, multilineage differentiation potential, and immunomodulatory properties by secreting multiple soluble factors. Thereby, MSCs promote tissue regeneration and neoangiogenesis, reduce inflammation, and prevent fibrosis and apoptosis. Further, these cells stimulate local stem cells to develop new tissue.

Figure 3.

advantages of engineered MSC therapy in GVHD. Different types of engineered mesenchymal cells, as well as the clinical and therapeutic outcomes of this type of cell therapy in GVHD, are shown. Genetic engineering of MSCs is aimed at improving their survival and engraftment as well as enhancing their repair mechanisms. Being easily isolated, having multilineage differentiation capacity،“manipulated ex vivo” and homing into the injury area are considered as features of engineered MSC. Upon genetic modification, they gain improved therapeutic functionalities of increased injury repair and disease recovery.