Stromal cells are an important part of the body's immune response and modulate inflammation through multiple pathways.
[1] In addition, by regulating local cytokine networks (e.g. M-CSF,[2] LIF[3]), bone marrow stromal cells have been described to be involved in human hematopoiesis and inflammatory processes.
Without a strong definition studies could not cross over or gain knowledge from each other because a stromal cell was not well defined and went by a plethora of names.
The cells must express CD73, CD90 and CD105 and they must be negative for CD14 or CD11b, CD34, CD45, CD79 alpha or CD19 and HLA-DR.[6] Low levels of human leukocyte antigen (HLA-DR) make MSCs hypoimmunogenic.
[5] They can also display anti-inflammatory as well as proinflammatory responses allowing for the potential to help with a broad range of immune disorders and inflammatory diseases.
During normal wound healing processes, the local stromal cells change into reactive stroma after altering their phenotype.
[9] In comparison to non-reactive stromal cells, TASCs secrete increased levels of proteins and matrix metalloproteinases (MMPs).
Tumor stromal production exhibits similar qualities as normal wound repair such as new blood vessel formation, immune cell and fibroblast infiltration, and considerable remodeling of the extracellular matrix.
[9] Furthermore, the tumor stroma is primarily composed of the basement membrane, fibroblasts, extracellular matrix, immune cells, and blood vessels.
These changes include the formation of carcinoma-associated fibroblasts (CAFs) which comprises a major portion of the reactive tissue stroma and plays a critical role in regulating tumor progression.
For example, they can inhibit the proliferation and activity of T-cells [12] When there is a high level of MSCs during an immune response the generation of more B-cells is stunted.
[7] Dendritic cells in the presence of MSC's are immature and undifferentiated which causes impaired function to call upon T-cells and bridge the gap between the innate and adaptive immune responses.
[16] [17] The secreted substances MSCs release an inflammatory response is stimulated include for example nitric oxide (NO), indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), programmed death-ligand 1 (PD-L1) and many more.
[19] If IFN-gamma and TNF-alpha are present in high levels the MSCs will stimulate an anti-inflammatory response by activating CD4, CD25, FoxP3, and Treg cell instead of cytotoxic T-cells.
However, MSCs with -IL-6 in the presence of monocytes induce M1-macrophages and can activate T-cells and produce high levels of IFN-gamma and TNF-alpha which regulates the inflammation through the previously mentioned mechanism.
[20] The body tells the MSCs what blood elements are needed and it conveys those adhesion molecules to the differentiating cell.
There is promising research in the fields of autoimmune disorders such as multiple sclerosis and rheumatoid arthritis as well as wound healing, COPD, and even acute respiratory distress syndrome[23] (an effect of COVID-19).
Stromal cells have the unique ability to create an immune modulated environment in order to best respond to foreign and known particles.