Stem cells are unique cells capable of self-renewal and differentiation into various specialized cell types. These capabilities make them a subject of intense scientific interest for their potential in treating diseases and repairing damaged tissues. Unlike many transplanted tissues, certain stem cells are often not rejected by the body’s immune system after surgery. This immune acceptance is a key factor enabling their use in regenerative medicine.
How the Body Identifies Foreign Cells
The body maintains a sophisticated defense system, the immune system, designed to distinguish between its own components and foreign invaders like bacteria, viruses, or transplanted cells. A central mechanism involves specialized proteins on cell surfaces known as Major Histocompatibility Complex (MHC) molecules, also called Human Leukocyte Antigens (HLA) in humans.
MHC molecules act like identification tags, presenting small protein fragments from within the cell to patrolling immune cells. There are two main classes of MHC molecules. Class I molecules are found on nearly all nucleated cells, signaling the cell’s internal state. Class II molecules are typically found on specific immune cells, presenting foreign protein fragments to initiate a broader immune response.
T-cells, a type of white blood cell, are crucial players in this recognition. They possess receptors that specifically bind to MHC molecules. If a T-cell recognizes a “foreign” protein fragment, it triggers an immune attack. This system ensures the body’s protection but challenges transplantation, as donor cells often display different MHC molecules.
Stem Cells’ Immune Evasion Strategies
Despite the immune system’s vigilance, certain types of stem cells, particularly Mesenchymal Stem Cells (MSCs), exhibit properties that allow them to evade rejection. One factor is their low immunogenicity. MSCs typically express low levels of MHC Class I molecules and often lack MHC Class II expression. This reduced display of “identification tags” makes them less visible to T-cells. Furthermore, MSCs generally do not express co-stimulatory molecules like CD40, CD80, and CD86, which are necessary for fully activating T-cells and initiating a strong immune response.
Beyond their low visibility, MSCs possess active immunomodulatory properties, meaning they can influence and suppress immune cell activity. They achieve this by secreting various soluble factors, including cytokines and growth factors. For instance, MSCs can produce transforming growth factor-beta (TGF-β), prostaglandin E2 (PGE2), indoleamine 2,3-dioxygenase (IDO), and interleukin-10 (IL-10). These molecules inhibit the proliferation and function of various immune cells, including T-cells, B-cells, and natural killer (NK) cells, creating a more tolerant environment.
Some studies suggest MSCs can induce apoptosis, or programmed cell death, in activated immune cells. Conversely, MSCs themselves may undergo apoptosis, and the subsequent uptake of these apoptotic MSCs by immune cells can reprogram those cells to become more anti-inflammatory. This dual action, being less recognized and actively suppressing immune responses, contributes to the reduced rejection of these stem cells.
The Advantage of Personalized Stem Cell Sources
A direct approach to avoiding immune rejection involves using the patient’s own cells for transplantation. This strategy, known as autologous transplantation, utilizes stem cells harvested from the individual and reintroduced into the same person. Since these cells originate from the patient, they carry the exact same MHC/HLA markers, ensuring recognition as “self” by the immune system. This eliminates the risk of immune rejection, a challenge in transplants involving donor cells.
Another method for personalized stem cell therapy involves induced Pluripotent Stem Cells (iPSCs). These are generated by reprogramming a patient’s adult somatic cells, such as skin cells, back into a pluripotent state, similar to embryonic stem cells. Because iPSCs are derived from the patient’s own genetic material, therapies using iPSC-derived cells were expected to be immune-compatible and avoid rejection. This patient-specific approach holds promise for regenerative medicine, offering various cell types without the need for immunosuppressive drugs typically required for allogeneic (donor) transplants. However, some research indicates that even autologous iPSCs can sometimes trigger an immune response due to potential genetic mutations or the expression of certain immunogenic proteins that arise during the reprogramming and culture process.