Immunomodulation of Human Adipose-Derived Mesenchymal Stem Cells

  • November 21, 2025 3:47 AM PST

    Mesenchymal stem cells (MSCs) have applications in the treatment of diverse disorders. They were first identified in bone marrow. However, their extraction from bone marrow was a complicated process, which fueled the research on discovering other MSC sources. Over the years, different sources of MSCs have been found, such as umbilical cord, adipose tissue, and dental pulp. Among them, adipose tissue has gained preference for its easy isolation and higher availability. Adipose tissue provides a much higher cellular yield than bone marrow, which is beneficial for research and therapy purposes. Therefore, numerous clinical trials have utilized adipose-derived MSCs for treating neurological disorders, cardiovascular issues, bone regeneration, diabetes, etc. 

    Human Adipose-derived Mesenchymal Stem Cells (AD-MSCs)

    Human Adipose-derived Mesenchymal Stem Cells are multipotent adult stem cells present in the adipose tissue located in the visceral and subcutaneous regions. The term to define this cell population varies from AD-MSCs to adipose stem cells (ASCs) or adipose-derived stromal cells (ADSCs). In comparison to bone marrow MSCs, adipose tissue cells demonstrate longer lifespan in culture and higher proliferative capacity. Their differentiation expands further from MSC-lineages to hepatocytes, epithelial cells, neurons, cardiomyocytes, pancreatic islets, and endothelial cells. 

    The extraction procedure involves liposuction surgery or lipoaspiration- a minimally invasive, safe, and cost-effective procedure. The amount of stem cells in the adipose tissue aspirate is also higher than that of the bone marrow aspirate. Studies have calculated that per mL marrow aspirate comprises 0.001-0.01% stem cells, whereas the percentage in adipose tissue is 1-10%. It gives an approximate value of 1 × 10^5 stem cells per gram of tissue. 

    Immunomodulation by Adipose Stem Cells

    Self-renewal and multi-lineage differentiation have been the defining features of AD-MSCs. In addition, these cells also possess immunomodulatory properties, that is, they secrete cytokines to regulate immune response. According to a few studies, they release an increased number of cytokines in comparison to their bone marrow counterparts. Additionally, they release prostaglandin E2 (PGE2) and IDO, which have immunomodulatory properties. For instance, PGE2 induces macrophages to produce IL10 to inhibit NK cells and T helper lymphocytes.

    Furthermore, AD-MSCs lack CD80, CD86, MHC II, CD40, CD40L, etc. which suppresses T lymphocyte activation during allogeneic transplant. They also inhibit the proliferation and differentiation of B lymphocytes, which prevents graft-vs-host disease. While the absence of specific surface proteins on AD-MSCs suppresses immune response, the presence of proteins on HLA-G5, PDL1, and galectins induces immunogenic tolerance. HLA-G5 inhibits dendritic cells, natural killer (NK) cells, and T lymphocytes. PDL1 and galectin are immune checkpoint regulators that subdue immune responses.

    Factors Affecting Immunomodulation

    The immunosuppression ability of AD-MSCs is remarkable. These cells can induce the proliferation of CD5+ B regulatory lymphocytes. However, this ability is dependent on several factors. Studies have reported that at late passage, the expression of MHC II, CD80, and CD86 upregulates in AD-MSCs, driving T lymphocyte proliferation. Another research inferred that AD-MSCs from female donors are more potent immunomodulators than those of male donors. It even showed the gender-based difference in the molecules that regulate immune response. 

    Moreover, research has found that dosage and timing of infusion also alter their properties. Many studies have also demonstrated that the cellular process and yield are influenced by the location of the tissue used for cell extraction. For instance, there is reduced apoptosis in abdominal AD-MSCs. These findings imply that donor features, treatment regimen, and extraction site affect the consistency of the therapeutic effect.

     

    Enhancing Immunomodulation

     

    Different approaches are under investigation for improving the immunomodulatory property of AD-MSCs. A study demonstrated that IFNγ produced by activated T lymphocytes primes AD-MSCs against T lymphocyte proliferation. Therefore, preconditioning with diverse inflammatory mediators such as IFNγ, TNFα, IL1, IL2, etc. can augment the ability to govern immune response. For instance, IL1β-primed AD-MSCs can suppress joint inflammation. A different concept is to retain the immunomodulation ability of AD-MSCs through their 3D culture. The spheroid culture has exhibited increased efficacy in controlling immunity. Moreover, their genetic manipulation can also confer heightened immune regulation. Integrating hypoxia-inducible or inflammation-sensitive promoters can trigger cytokine secretion in specific disease signals. 

    Conclusion

    Adipose tissue has been an attractive source of MSCs. The minimally invasive extraction procedure and high cell yield have fueled its applications in clinical trials. Their immunomodulatory properties have therapeutic potential for autoimmune and inflammatory disorders. Additionally, this property also prevents immune rejection and GVHD after allogenic transplant. Moreover, this property can be augmented through different strategies for better efficacy.

    However, it should be noted that their therapeutic ability might vary with different factors, including donor attributes. It could contribute to the different responses often observed in clinical trials or research studies. AD-MSCs belonging to different donors are also affected by age and environment. Therefore, considering these factors in mind before their isolation can maximize the consistency of the cells. Advancells maintains the consistency standards while offering Human Adipose-Derived Mesenchymal Stem Cells at early passage with relevant documentation of the donor.