2.4. The comparison of multidirectional differentiation ability
The multi-directional differentiation ability of BM-MSC, UC-MSC and UCB-MSC can be compared by identifying adipogenic and osteogenic differentiation of MSCs from three different sources under specific conditions. Vonkossa Identification of osteoblasts by staining reverse transcription-polymerase chain reaction (RT-PCR) showed that under specific conditions, MSCs from three different sources can be induced to differentiate into adipocytes and there was no significant difference in their differentiation ability.
3. The role of mesenchymal stem cells in the process of immune regulation
Mesenchymal stem cells not only have the potential for self-replication and multi-directional differentiation, but also have low immunogenicity and immunomodulatory effects. They have a wide range of sources and have broad clinical application prospects. Mesenchymal stem cells have a strong immunosuppressive effect on adaptive immunity and innate immunity. The suppressive effect of mesenchymal stem cells on adaptive immunity is mainly manifested in the immunosuppressive effects on T lymphocytes and B lymphocytes, and the suppressive effect on innate immunity is mainly manifested in immunosuppressive effects of monocytes/macrophages, dendritic cells, and natural killer cells. The following introduces the immunomodulatory effects of MSCs on T lymphocytes, B lymphocytes, NK cells, and dendritic cells and their clinical application prospects.
3.1 The immunomodulatory effect of mesenchymal stem cells on T cells
T cells are pluripotent stem cells derived from bone marrow, which differentiate and mature in the thymus. They are the most numerous and most complex type of lymphocytes. In the absence of antigen challenge, effector T cells are in the form of resting cells that are not activated. After the antigen enters the body, under the action of antigen-presenting cells or target cells, the resting T cells are activated and proliferated and differentiated into effector T cells to exert cellular immunity. Activation of effector T cells requires dual signals. After the combination of effector T cells with the antigen-presenting cell or target cell membrane MHC class molecule with antigen peptide molecule complex, the first signal can be transmitted through the CD3 complex molecule. And the other auxiliary molecules on T cells such as CD2, LFA-1, CD8 and CD28 can interact with corresponding ligand molecules on antigen-presenting cells or target cells such as LFA-3, ICAM-1, MHC class I molecules, and B7 molecules, and transmit synergistic signals to effector T cells and activate them.
Mesenchymal stem cells inhibit T cell division and proliferation. Mesenchymal stem cells can block the T cell cycle and keep T cells in G0 / G1 phase. At the molecular level, T cell cyclin expression increases, while P27 expression decreases. Different studies have different conclusions about whether mesenchymal stem cells can induce T cell apoptosis. Some studies believe that mesenchymal stem cells have no effect on the apoptosis of T cells, some studies believe that mesenchymal stem cells can induce apoptosis of T cells, and even some studies believe that mesenchymal stem cells have a protective effect on T cell apoptosis. At the same time, studies have shown that mesenchymal stem cells can also inhibit the activation of T cells. In short, the mechanism of T-cell immunosuppression by mesenchymal stem cells needs further research to prove.
Cytokines related to the immune regulation of mesenchymal stem cells mainly include transforming growth factor β, hepatocyte growth factor, prostaglandin E2, interleukin 10, indolamine 2, 3-dioxygenase (IDO), nitric oxide, heme oxygenase 1, HLA-G, etc. Indoleamine 2,3-dioxygenase participates in tryptophan metabolism and causes tryptophan deficiency, thereby inhibiting T cell activity. Nitric oxide inhibits T cell activity by inhibiting dendritic cell maturation and tumor necrosis factor-alpha secretion. HLA-G inhibits T cell activity through interaction with the receptors.
The interaction between mesenchymal stem cells and T cells is not only related to the role of soluble factors, but also related to the interaction between cells. During the contact between mesenchymal stem cells and T cells, mesenchymal stem cells mainly inhibit the proliferation of T cells through the interaction of programmed death factor 1 and its ligands. Mesenchymal stem cells express the B7-H1 molecule, and after interacting with CD28, they block the T cell co-stimulatory pathway and suppress the immune response. Mesenchymal stem cells inhibit the proliferation of T cells through cell contact.
The inhibitory effect of mesenchymal stem cells on T cells is also concentration-dependent. The higher the ratio of mesenchymal stem cells to T cells, the stronger the inhibitory effect on T cells. Other studies have shown that when the ratio of mesenchymal stem cells to T cells is reduced to a certain level, it can also exhibit a certain immune stimulating effect. This immunostimulatory effect mainly occurs in the experiment of co-culture of mesenchymal stem cells and T cells stimulated by CD3 / CD28 antibody. The researchers believe that CCL2 plays an important role in the stimulation of T cells at a low ratio of mesenchymal stem cells to T cells (10: 1). CCL2 stimulates T cell proliferation through the interaction of CCR2 expressed in activated T cells.
To be continued in Part III…