Immunomodulatory properties of human placental mesenchymal stem/stromal cells
Introduction
Mesenchymal stem/stromal cells (MSCs) are multipotent adult stem cells that are isolated from different fetal and adult tissues, such as adipose tissue, umbilical cord, bone marrow and placenta [1], [2], [3]. MSCs are spindle-shaped cells that adhere to plastic and form colonies called colony-forming unit (CFU) [1], [2], [3]. MSCs differentiate into cell derivatives of the mesenchymal lineage, including adipocytes, osteocytes and chondrocytes [1], [2], [3]. In cell culture, MSCs can be stimulated to trans-differentiate into hepatocyte-, neuron- and astrocyte-like cells [4].
The therapeutic potential of MSCs has been attributed to their differentiation potential. In addition, their immunomodulatory properties make them highly attractive for treating immune disorders such as multiple sclerosis (MS) and graft versus host disease (GVHD). GVHD occurs when the transplanted donor's immune system attacks the recipient's immune system, usually after allogeneic bone marrow transplantation, but occasionally after homologous blood transfusion [5].
The placenta is a fetomaternal organ that allows the protection, and the growth of the developing fetus. It consists of chorionic and basal plates that are fetal and maternal surfaces, respectively [6]. The chorionic plate consists of the chorionic villous tree, and the basal plate consists of the decidua basalis, which is endometrial tissue transformed during pregnancy to allow attachment of the placenta [6], [7]. Moreover, during pregnancy these plates merge to form the fetal membranes, which consists of the amnion and the chorion [1]. The amnion consists of an epithelial layer with an underlying stromal layer, and the chorion consists of a stromal layer [1]. As the fetus grows, the chorion of the fetal membranes adheres to the overlying decidua parietalis to form the choriodecidua [1]. MSCs can be isolated from each of these regions.
We are others isolated MSCs from various parts of human placenta (pMSCs) such as chorionic villous, decidua basalis, decidua parietals and amniotic membrane [1], [2], [3], [8]. In common with MSCs from other sources, pMSCs display immunomodulatory properties, which make them potentially useful for immune-mediated diseases, and therefore pMSCs are intensively studied.
Section snippets
pMSCs express major histocompatibility complex (MHC) class molecules
MSCs express major histocompatibility complex (MHC) class I but not MHC class II. Unstimulated MSCs from the placenta and other sources such as bone marrow (BMMSCs), umbilical cord (UCMSCs), adipose tissue (ADMSCs) express MHC class I but not MHC class II antigens [1], [2], [3], [9], [10]. However, following stimulation with interferon-γ; (IFN-γ), BMMSCs, UCMSCs, and ADMSCs upregulate the expression of MHC class II both in vitro and in vivo [10], [11], [12], [13], [14], [15], [16], [17]. There
T cells
The immunosuppressive effects of pMSCs on T lymphocytes are the most commonly studied. T lymphocytes are part of the adaptive immune system and play an essential role in cell mediated immunity. Increasing reports show the potent immunosuppressive properties of pMSCs are dependent on their ability to inhibit the proliferation and cytokine production of allogeneic lymphocytes. pMSCs inhibit the proliferative response of allogeneic lymphocytes in a mixed lymphocyte reaction (Fig. 1) [23], [24],
Mechanisms mediating the immunosuppressive functions of pMSCs
Several immunosuppressive mechanisms of pMSCs have been reported as described below.(See Table 2)
pMSCs in vivo and their clinical potential to treat immune-mediated diseases
Several studies addressed the survival and immunosuppressive abilities of pMSCs when administered in vivo. The immunosuppressive effects of pMSCs on the severity of bleomycin-induced inflammation and fibrosis in animal models was evaluated in several studies. The transplantation of pMSCs into mice with lung fibrosis reduced neutrophil infiltration, which was associated with reduced inflammation and amelioration of disease severity [77]. In addition, conditioned medium from pMSCs reduced lung
pMSCs in clinical trials
Currently, there are about 682 clinical trials involving MSC transplantations, and 10 clinical trials involving pMSC transplantations that are registered at the clinicaltrials.gov website (http://www.clinicaltrials.gov/). These clinical trials investigate the potential of using pMSCs in the clinic. The majority of these studies depend on the immunomodulatory properties of pMSCs. Although some of these trials are not yet completed, thus far the results support the biosafety of MSC
Conclusion
pMSCs exert their immunosuppressive functions by secreting soluble factors, but the characteristics of the soluble factors produced by pMSC or the mechanisms through which these cells act are still unclear. pMSCs can modulate the immune functions of macrophages and dendritic cells causing inhibition of T cell proliferation, or by increasing the generation of Tregs. The precise mechanisms of the immunosuppressive activities of pMSCs in vivo are still unclear. Nevertheless, there is increasing
Conflict of interest
The authors declare no potential conflicts of interest.
Acknowledgements
We wish to acknowledge the financial support of the KAIMRC Grant No. RC12/117.
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