Mesenchymal Stromal Cells: Clarifying the Term “Stem Cell”

In the growing field of regenerative medicine, mesenchymal stromal cells (MSCs) have emerged as key players due to their immunomodulatory properties and ability to facilitate tissue regeneration. However, the widespread use of the term “stem cell” to refer to MSCs has sparked debate within the scientific community due to its implications for their definition and functionality.

Historical Roots of the Term “Stem Cell”

The term “stem cell” (from the German Stammzelle) was first used in the 19th century to describe primitive cells capable of giving rise to different cellular lineages. In the late 20th century, Dr. Arnold Caplan coined the term “mesenchymal stem cells” or MSCs to describe bone marrow-derived cells with the capacity to differentiate into mesodermal lineages such as bone, cartilage, and fat. This nomenclature quickly captured the attention of the scientific and medical sectors, fueled by the excitement over MSCs’ regenerative potential.

As research progressed, it became clear that the term “stem cell” could be misleading. While MSCs possess some differentiation capacity, their primary mechanism of action in cell therapies is paracrine, meaning they secrete bioactive factors that promote regeneration and modulate the immune system, rather than differentiating directly into specific tissues.

Recognizing this limitation, Dr. Caplan suggested renaming MSCs as “medicinal signaling cells” to highlight their true therapeutic contribution. This change not only clarifies their functionality but also adjusts expectations for their clinical applications.

Clinical Relevance of Terminological Precision

Why Does Terminology Matter?

Confusion surrounding terminology can influence the expectations of physicians and patients regarding “stem cell” treatments, leading them to believe that MSCs directly regenerate damaged tissues. Instead, their ability to reduce inflammation, modulate immune responses, and promote tissue repair through bioactive signaling is what truly makes them a powerful therapeutic tool.

The term “stem cell” has contributed to misconceptions about MSCs. Although they have some differentiation capacity, their plasticity is more limited compared to pluripotent stem cells such as embryonic stem cells. MSCs meet specific criteria established by the International Society for Cellular Therapy, including adhesion to plastic culture surfaces, a defined surface marker profile (positive for CD105, CD73, and CD90; negative for CD45 and CD34), and the ability to differentiate into osteoblasts, adipocytes, and chondrocytes.

Thus, it is essential to inform readers about the true potential of these cells, which lies in their immunomodulatory properties and their ability to facilitate tissue regeneration through the secretion of bioactive factors (the secretome).

Minimum Criteria for MSCs

In 2006, the International Society for Cellular Therapy (ISCT) established criteria to define MSCs:

1. Plastic Adherence: MSCs must adhere to standard culture flasks under typical culture conditions.
2. Specific Surface Markers: MSCs must express CD105, CD73, and CD90 while lacking hematopoietic markers such as CD45, CD34, CD14, and HLA-DR.
3. Differentiation Capacity: MSCs must demonstrate the ability to differentiate into osteoblasts, adipocytes, and chondroblasts under standard in vitro culture conditions.

These criteria highlight the unique properties of MSCs but do not resolve the debate over whether they should be classified as true stem cells.

Challenges with the Term “Stem Cell”

The use of “stem cell” in MSC nomenclature often implies a level of plasticity and regenerative capacity akin to embryonic or induced pluripotent stem cells, which is not entirely accurate. MSCs are, at best, multipotent, and their therapeutic effects are primarily attributed to their immunomodulatory and trophic activities rather than their capacity to regenerate tissues through differentiation.

Moreover, the term “stem cell” has been exploited in commercial settings, leading to misunderstandings and inflated expectations among physicians and patients. Many clinics advertise “cell-based therapies” with vague claims about the benefits of “stem cells,” often without adhering to rigorous scientific standards.

From the Lab to the Clinic

Clinical interest in MSCs continues to grow, with over 700 registered clinical trials exploring their application in a variety of immunological and inflammatory diseases. Even in small doses, MSCs have shown the ability to trigger significant therapeutic responses due to their paracrine action and capacity to modulate inflammatory microenvironments.

MSCs have demonstrated a critical role in regenerative medicine—not only for their ability to differentiate into mesodermal lineages but also for their exceptional immunomodulatory properties. These cells provide a promising tool to manage excessive inflammatory responses and treat autoimmune diseases. This article explores how MSCs impact the immune system and highlights their potential in clinical applications.

From Regeneration to Immunomodulation

Although MSCs have traditionally been studied for their capacity to regenerate tissue, recent research has revealed that their primary therapeutic function lies in their immune-modulating ability. MSCs influence the inflammatory response by secreting soluble factors such as prostaglandin E2 (PGE2) and interleukin-10 (IL-10), as well as through direct cell-to-cell interactions. These mechanisms enable MSCs to regulate both innate and adaptive immunity, mitigating excessive inflammatory responses.

Their most notable actions include suppressing T-cell activation and proliferation, inhibiting the differentiation of pro-inflammatory dendritic cells, and inducing macrophages with an anti-inflammatory M2 phenotype. This range of immunomodulatory effects positions MSCs as a valuable therapeutic tool for conditions such as graft-versus-host disease, lupus, rheumatoid arthritis, and inflammatory bowel diseases.

In cases of acute inflammation, MSCs have the ability to migrate to sites of tissue damage. Once there, they regulate the release of pro-inflammatory cytokines like TNF-α and IFN-γ, promoting tissue repair and protecting surrounding cells from damage. In models of autoimmune diseases such as multiple sclerosis and Crohn’s disease, MSCs have been shown not only to reduce active inflammation but also to induce immune tolerance, lowering symptom recurrence.

The use of extracellular vesicles released by MSCs, loaded with bioactive factors, represents an emerging area of research that promises to maximize the therapeutic impact of these cells.

The Potential of MSCs in Personalized Therapies

The versatility of MSCs allows for the development of personalized therapeutic strategies. At Baja Regenerative, we harness their properties to create innovative therapies aimed not only at regenerating damaged tissues but also at regulating aberrant immune responses.

MSCs can be administered locally to treat specific inflammation, such as in cases of osteoarthritis, or systemically for generalized autoimmune conditions.

 

Conclusion

At Baja Regenerative, we are committed to providing clear, evidence-based information about MSCs, highlighting their true potential and the clinical applications supported by rigorous science.

The debate over MSC terminology is not trivial and goes beyond academic discussion; it is essential for building trust and transparency in the field of regenerative medicine. Accurately defining them also fosters more informed and effective use of these cells in clinical contexts. MSCs, as “medicinal signaling cells,” represent a transformative tool for regeneration and managing inflammatory diseases.

Mesenchymal stromal cells are far more than regenerative tools—they are potent mediators of immunity. With growing evidence supporting their effectiveness, MSCs represent an invaluable opportunity to address a wide range of inflammatory diseases. At Baja Regenerative, we work to ensure these therapies are safe, effective, and accessible, supported by solid science.

To learn more about our cellular therapies and how MSCs can benefit your health, contact us today! We are here to guide you every step of the way on this exciting journey toward wellness.

If you’d like to explore more about our cellular therapies, contact us and discover how MSCs may hold the key to transforming your health and well-being.

 

References

• Ramalho-Santos, M., & Willenbring, H. On the Origin of the Term ‘Stem Cell.’ Cell Stem Cell, (2007).
• Andrzejewska, A., Lukomska, B., & Janowski, M. Mesenchymal Stem Cells: From Roots to Boost. Stem Cells. (2019).
• Dominici, M., et al. Minimal Criteria for Defining Multipotent Mesenchymal Stromal Cells. Cytotherapy. (2006).
• Tajbakhsh, S. Stem Cell: What’s in a Name? Nature Reviews. (2009).
• Nauta, A. J., & Fibbe, W. E. Immunomodulatory properties of MSCs. Blood, 110(10), 3499-3506. (2007).
• Cagliani, J., et al. Immunomodulation by MSCs and their clinical applications. J Stem Cell Regen Biol. (2017).
• Pistoia, V., & Raffaghello, L. Mesenchymal stromal cells and autoimmunity. Int Immunol, 29(2), 49-58. (2017).
• Brooks, A., et al. Quantitative detection and modeling the in vivo kinetics of therapeutic MSCs. Stem Cells Translational Medicine, 7(1), 78-86. (2018).

 

Author: Jose Luis Flores Sevilla, MSc. PhD. Molecular Biomedicine.