Stromal Cells Role in Immunoregulatory Function

Stromal cells are the connective tissue cells for all organs in the human body. The most common types these cells in our bodies are Pericytes and Fibroblasts (skin cells)

Stromal cells can be found in:

• Liver
• Kidneys
• Mucous membranes
• Lymph nodes
• Prostate
• Ovaries
• Bone marrow
• Adipose Tissue
• Pancreas

The primary function of the stromal cells are to support functions of the parenchymal cells of the specific organ in which they are found.[1] Widely used today in regenerative medicine centers are MSCs cells or Mesenchymal stem cells which are essentially multipotent stromal cells and used in many stem cell therapies including spinal cord injuries and burst fractures in the cervical and lumbar spine. ^[2] Stromal cells posses broad immunoregulatory properties.

Stromal cells are a diverse group of connective tissue cells that provide structural support to the organs in which they reside. Unlike the functional cells of a tissue (often referred to as the parenchymal cells), stromal cells mainly serve supportive, architectural, and nutritive functions. They are a critical component of the tissue microenvironment and are particularly important in the context of stem cell niches and immune cell function.

Types of Stromal Cells

Stromal cells can be classified based on the tissue or organ where they are found. Some common types include:

• Fibroblasts: These cells are responsible for synthesizing the extracellular matrix and collagen, providing structural support to tissues.
• Adipocytes: These are fat cells that store energy and provide insulation.
• Endothelial Cells: These cells line the interior surface of blood vessels and lymphatic vessels.
• Pericytes: These cells wrap around endothelial cells in capillaries and venules throughout the body.
• Mesenchymal Stromal Cells (MSCs): These multipotent stromal cells can differentiate into a variety of cell types, including osteoblasts, chondrocytes, and adipocytes.

Functions of Stromal Cells

• Structural Support: Stromal cells produce the extracellular matrix, a three-dimensional network of macromolecules that provide structural support to cells.
• Cell Signaling: Stromal cells are involved in signaling pathways that regulate cell growth, differentiation, and immune response.
• Nutrient Supply: These cells often support the delivery of nutrients to tissues and can also modulate inflammation.
• Niche Formation: In the context of stem cells, stromal cells help form the “niche” or microenvironment that keeps stem cells in an undifferentiated state or triggers their differentiation.

Importance of Stromal Cells in Medicine

Stromal cells are becoming increasingly significant in various medical applications:

• Regenerative Medicine: Mesenchymal stromal cells are being investigated for their potential to repair or regenerate damaged tissues.
• Cancer Research: Stromal cells can be co-opted by tumors to help them grow and spread, so understanding the interaction between stromal and cancer cells may offer new avenues for treatment.
• Immunology: In immune organs like the lymph nodes and spleen, stromal cells play a crucial role in regulating immune responses.

Current Research and Challenges

While stromal cells hold immense therapeutic potential, especially in the fields of regenerative medicine and oncology, further research is needed to fully understand their complex roles in different tissues and pathological conditions. Stromal cells are unique in cancer research also. The general interaction between cancerous tumor cells and stromal cells is what is believed to play a significant role in cancer growth and development.^[3]

Fibroblast Stromal cells in the epidermis (outer) layer of our skin constantly releases immuno growth factors that help promote cell division that keeps our skin healthy and fresh. Certain skin cancers such as basal cell carcinoma cannot spread throughout the body because the cancer cells require nearby stromal cells beyond the skin areas to continue its constant division. By removing these stromal cell growth factors in certain instances we can prevent some cancers from spreading themselves to other vital organs. Stromal cells serve as the “soil” in which the “seeds” of functional cells in tissues grow and thrive. Their supportive role extends not just to structural integrity but also to the regulation of crucial biological processes. Understanding the various functions of stromal cells could greatly advance our approaches to tissue engineering, regenerative medicine, and cancer therapy.

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Published Clinical Citations

[1] ^ Anna-Maaria Vähä, Anniina Veijola, Henna Karvonen, Siri Lehtonen, Riitta Kaarteenaho, P053 Variable effect of pirfenidone, nintedanib and N-acetylcysteine solely and combined on stromal cells of different types of pulmonary fibroses , QJM: An International Journal of Medicine, Volume 109, Issue suppl_1, September 2016, Page S39, https://doi.org/10.1093/qjmed/hcw124.025

[2] ^ Karen English, Mesenchymal stromal cell therapy for pulmonary fibrosis , QJM: An International Journal of Medicine, Volume 109, Issue suppl_1, September 2016, Page S30, https://doi.org/10.1093/qjmed/hcw119.030

[3] ^ J. Stolk, W. Broekman, T. Mauad, J.J. Zwaginga, H. Roelofs, W.E. Fibbe, J. Oostendorp, I. Bajema, M.I.M. Versteegh, C. Taube, P.S. Hiemstra, A phase I study for intravenous autologous mesenchymal stromal cell administration to patients with severe emphysema, QJM: An International Journal of Medicine, Volume 109, Issue 5, May 2016, Pages 331–336, https://doi.org/10.1093/qjmed/hcw001