Stem cells are unique cells with the ability to renew themselves and develop into various specialized cell types, such as muscle cells or brain cells. They are present in almost all body tissues and contribute to tissue maintenance and repair after injury. The body typically mounts a strong defense against anything it perceives as foreign, leading to rejection. However, stem cells often appear to be an exception to this rule, prompting questions about how they can be used in medical procedures without triggering an immune response.
Understanding Immune Rejection
The body’s immune system protects it from threats. It distinguishes between its own cells (“self”) and foreign entities (“non-self”). This relies on Major Histocompatibility Complex (MHC) molecules on cell surfaces.
MHC molecules function like identification tags, displaying small fragments of proteins from inside the cell to the immune system. There are two main types: MHC Class I molecules, found on nearly all nucleated cells, and MHC Class II molecules, primarily found on specialized immune cells. If the immune system encounters cells presenting foreign protein fragments on their MHC molecules, it initiates an attack. This mechanism is why transplanted organs are often rejected unless the recipient’s immune system is suppressed.
The Autologous Advantage
Autologous stem cells, originating from the patient’s own body, can be used without triggering immune rejection. Harvested from the individual, they are genetically identical to the recipient’s existing cells.
The immune system recognizes these autologous cells as “self.” This inherent recognition means the body does not perceive them as foreign or mount an immune attack. This approach is similar to a skin graft, which is typically accepted without issue. Using autologous stem cells bypasses immune compatibility challenges, making them a straightforward option for certain therapies.
How Donor Stem Cells Evade Immune Detection
Donor-derived, or allogeneic, stem cells present a different challenge. Mesenchymal stem cells (MSCs) can avoid immune detection or suppress its response. MSCs are multipotent cells isolated from various tissues, such as bone marrow and adipose tissue. Their ability to modulate immune responses makes them valuable in regenerative medicine.
MSCs’ low immunogenicity means they are less likely to provoke an immune response. They express very low levels of MHC Class I molecules and typically lack MHC Class II molecules, crucial for immune cell recognition. This reduced expression makes them less “visible” to the recipient’s immune system, allowing them to go largely unnoticed. Even when stimulated by inflammatory signals, MSCs may upregulate MHC Class I but often do not express the co-stimulatory molecules needed to fully activate immune responses.
Beyond simply being less visible, MSCs also exhibit powerful immunomodulatory properties, meaning they can actively influence and dampen the activity of immune cells. They achieve this by secreting a variety of soluble factors, including cytokines and growth factors. These secreted molecules can suppress the proliferation and activity of various immune cells, such as T-cells, B-cells, and dendritic cells.
For example, MSCs can inhibit T-cell proliferation and shift immune responses towards a more anti-inflammatory state. They can also influence macrophages, promoting their polarization to an anti-inflammatory phenotype. This active “pacifying” of the immune system allows donor MSCs to survive and function within the recipient’s body without being aggressively attacked. The lack of co-stimulatory molecules, such as CD80 and CD86, on MSCs further ensures that even if they are recognized, the immune response cannot be fully activated, leading to a state of tolerance rather than rejection.