مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
The Role of Mesenchymal Stem Cells in Modulating Immune Response in Regenerative Medicine
The Role of Mesenchymal Stem Cells in Modulating Immune Response in Regenerative Medicine
Kasra Kordi,1,*
1. Islamic Azad University Tehran Medical Sciences
Introduction: Regenerative medicine, a rapidly evolving field, aims to restore tissue and organ function through the repair, replacement, or regeneration of damaged cells, with stem cells as key therapeutic agents. Mesenchymal stem cells (MSCs) are particularly notable for their capacity to differentiate into multiple tissues and modulate immune responses. Because cell-based therapies can induce immune reactions, regulating these responses is crucial for therapeutic success. This paper reviews the principles of regenerative medicine, the characteristics of MSCs, and their interactions with immune cells, emphasizing the potential of MSCs mediated immunomodulation to enhance regenerative outcomes.
Methods: Mesenchymal stem cells (MSCs) do not naturally differentiate directly into most immune cell types such as lymphocytes or macrophages; however, they can modulate immune responses indirectly. Some studies have explored protocols to induce MSC differentiation toward immune-like cells, such as macrophage- or dendritic cell-like phenotypes, primarily through specific growth factors, culture conditions, and chemical signals.
Key approaches include:
1. Use of Growth Factors and Cytokines: Supplementing culture media with factors such as GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor), M-CSF (Macrophage Colony-Stimulating Factor), IL-4, IL-6, and TNF-α to guide MSCs toward macrophage or dendritic cell lineages.
2.Specialized Culture Environments: Employing specific physical and chemical culture conditions, including three-dimensional (3D) culture systems and biomaterials, to enhance differentiation efficiency.
3.Co-culture Systems: Culturing MSCs alongside primary immune cells (e.g., macrophages) to promote differentiation via cell-to-cell signaling.
4. Chemical and Physical Stimuli: Applying chemical stimuli like lipopolysaccharide (LPS) or poly I:C, and physical stimuli such as mechanical stress or light exposure, to induce phenotypic changes.
Direct differentiation of MSCs into fully functional immune cells, especially lymphocytes, remains unproven and limited. The immunomodulatory role of MSCs is more established, acting primarily through secretion of soluble factors and extracellular vesicles to regulate immune cell behavior rather than direct replacement.
Results: Numerous studies have demonstrated that mesenchymal stem cells (MSCs) exert significant immunomodulatory effects on various immune cell types. MSCs inhibit T cell proliferation and activation through secretion of soluble factors such as transforming growth factor-beta (TGF-β), prostaglandin E2 (PGE2), and indoleamine 2,3-dioxygenase (IDO). They also promote the generation of regulatory T cells (Tregs), contributing to immune tolerance. Additionally, MSCs modulate the activity of dendritic cells by inhibiting their maturation and antigen-presenting capacity, thus dampening adaptive immune responses.
MSCs have been shown to suppress B cell proliferation and antibody production and to reduce natural killer (NK) cell cytotoxicity and cytokine secretion. Furthermore, MSCs influence macrophage polarization, promoting a shift from pro-inflammatory M1 to anti-inflammatory M2 phenotypes, which supports tissue repair and resolution of inflammation.
These immunoregulatory properties are mediated through both direct cell–cell contact and the release of extracellular vesicles containing bioactive molecules. Collectively, these mechanisms enable MSCs to create an anti-inflammatory microenvironment, reduce tissue damage, and enhance the success of regenerative therapies.
Conclusion: Mesenchymal stem cells (MSCs) play a pivotal role in regenerative medicine not only through their differentiation potential but also by their robust immunomodulatory capabilities. While direct differentiation of MSCs into immune cells remains limited, their ability to regulate immune responses via soluble factors, extracellular vesicles, and cell–cell interactions is well established. MSC-mediated modulation of T cells, B cells, dendritic cells, natural killer cells, and macrophages contributes to the suppression of harmful inflammation and promotion of tissue repair. Harnessing these immunoregulatory properties of MSCs offers promising avenues to overcome immune-related challenges in cell-based therapies and improve the efficacy and safety of regenerative treatments. Future research should focus on optimizing MSC-based immunomodulation strategies to maximize therapeutic outcomes in clinical applications.