What are Mesenchymal Stem Cell Markers?
Mesenchymal stem cell (MSC) markers are specific cell surface proteins used to identify and characterize these multipotent stromal cells.
The International Society for Cellular Therapy (ISCT) established minimal criteria for human MSCs, which include positive expression of CD73, CD90, and CD105, and negative expression of CD11b, CD14, CD19, CD34, CD45, CD79a, and HLA-DR.
Additional markers such as CD44, CD166, CD29, STRO-1, CD146, and CD271 are also commonly used, with their expression varying depending on the tissue of origin. Recent research has identified more specific markers for "true skeletal stem cells," including PDPN+, CD146-, CD73+, and CD164+, highlighting the ongoing refinement of MSC characterization.
Common MSC Markers
MSCs are adult stem cells that can differentiate into multiple cell types, including bone, cartilage, and fat cells. Commonly used MSC markers include:
- CD44: A cell adhesion molecule that is involved in cell-cell and cell-matrix interactions.
- CD73: An enzyme that is involved in the production of extracellular adenosine, which has anti-inflammatory effects.
- CD90: A glycoprotein that is involved in cell adhesion and signaling.
- CD105: A transmembrane glycoprotein that is involved in angiogenesis and bone formation.
- CD106: A cell adhesion molecule that is involved in leukocyte recruitment and inflammation.
- CD166: A cell adhesion molecule that is involved in cell-cell and cell-matrix interactions.
- Stro-1: A cell surface antigen that is expressed on bone marrow stromal cells and is involved in cell adhesion and signaling.
It is important to note that the expression of these markers can vary depending on the source of the MSCs and the culture conditions used. Additionally, the use of these markers to identify MSCs has limitations and challenges, as they are not specific to MSCs and can be expressed on other cell types.
Mesenchymal stem cell markers are like ID badges that help scientists recognize these special cells. The markers have names like CD44, CD73, and CD90, and each one has a specific job, like helping cells stick together or sending signals. However, these markers aren't perfect; they can sometimes appear on other cells too. Still, they're useful for research, especially when looking at how these cells can be used to heal the body in medical treatments.
Functions
Mesenchymal stem cell (MSC) markers serve several important functions:
- Identification and characterization: The primary function of MSC markers is to identify and characterize these cells. Specific combinations of surface proteins allow researchers to distinguish MSCs from other cell types.
- Isolation: Markers enable the isolation and purification of MSCs from heterogeneous cell populations. For example, positive markers like CD73, CD90, and CD105 can be used to select MSCs, while negative markers like CD45 and CD34 help exclude other cell types.
- Quality control: Markers provide a way to assess the purity and quality of isolated MSC populations. This is crucial for both research and clinical applications.
- Potency assessment: Some markers correlate with the differentiation potential and functional properties of MSCs. For instance, CD146 expression has been associated with multipotency.
- Tissue origin determination: Certain markers can help identify the tissue of origin for MSCs, as different sources (e.g., bone marrow, adipose tissue, dental pulp) may have slightly different marker profiles.
- Monitoring changes: Markers allow researchers to track changes in MSC populations during culture, differentiation, or other experimental manipulations.
- Standardization: The International Society for Cellular Therapy has established minimal criteria for MSC identification based on specific markers, helping to standardize research and clinical practices across different laboratories.
- Functional insights: Some markers provide clues about the functional properties of MSCs, such as their immunomodulatory capabilities or their potential roles in tissue repair.
By serving these functions, MSC markers play a crucial role in advancing our understanding of these cells and their potential therapeutic applications in regenerative medicine and other fields.
Therapeutic Application
Contribution of markers for mesenchymal stem cells to the therapeutic applications described above:
- Identification and isolation: Identification and isolation of MSCs from heterogeneous cell populations are possible due to the specific combination of surface markers; this aids researchers and clinicians in isolating pure MSC populations for therapeutic use.
- Means of quality control: Markers provide a means to assess the purity and quality of isolated MSC populations. This will ensure that cells utilized in clinical applications are safe and efficient.
- Potency testing: A small number of markers are linked with the differentiation potential of MSCs and functional characteristics. Such information can be used to assess the therapeutic potential of cells for specific use.
- Standardization: The International Society for Cellular Therapy developed minimal criteria for characterizing MSCs based on particular markers. This has made research and clinical applications standardized across different laboratories and clinical trials.
- Monitoring changes: Markers enable the monitoring of changes arising in the MSC population in culture, following differentiation or other manipulations. This is necessary to better understand the behavior and change of the cells during the preparation process for clinical application.
- Determination of tissue origin: Certain markers will help determine the tissue origin of an MSC. This is important since MSCs derived from different sources might bear slightly different properties and therapeutic potentials.
- Insights into functions: Some markers hint at the tasks that a particular MSC can perform, for example, their immunomodulatory capabilities or potential roles in tissue repair. Such information then guides the selection of MSCs for appropriate therapeutic application.
- Safety assessment: The expression or non-expression of the selected markers gives rise to the condition where the cell population lacks cell types that might be harmful and, therefore, will enhance the safety profile of MSC-based therapeutic strategies.
By performing these functionalities, the markers of the MSC now become fundamentally crucial in taking forward the therapeutic applications for these cells in the fields of regenerative medicine and immunomodulation, among other clinical fields. This ensures that the appropriate cells are used for the intended application, increasing the overall safety and effectiveness of treatments involving MSCs.
Importance for Safety
MSC markers play many important roles in the safety of cell therapy. By checking for specific markers, researchers can verify they're using pure, high-quality MSCs and not other potentially harmful cell types.
These markers also allow scientists to assess the cells' therapeutic potential and track any changes during the manufacturing process, ensuring the final product remains safe and effective.
This standardized approach to identifying and characterizing MSCs using markers is crucial for maintaining consistent safety and quality standards across different laboratories and clinical trials, ultimately benefiting patients receiving these innovative treatments.
Conclusion
Mesenchymal stem cell (MSC) markers play a crucial role in standardizing the classification and quality control of these cells across the industry.
By establishing a set of specific surface proteins to identify and characterize MSCs, researchers and clinicians aim to ensure consistency, safety, and efficacy in cell therapy treatments.
These markers serve as a common language for laboratories worldwide, helping to maintain high standards in MSC isolation, cultivation, and application. For patients seeking MSC treatments, it's important to be aware of these standardization efforts.
When considering a clinic or treatment, patients should inquire about the facility's quality control methods and ask if they can provide evidence of third-party or internal testing that confirms the presence of appropriate MSC markers. This information can help ensure that the cells being used meet established criteria for identity, purity, and potency, ultimately contributing to safer and more effective cell therapies.
References
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(3) Maleki M, Ghanbarvand F, Reza Behvarz M, Ejtemaei M, Ghadirkhomi E. Comparison of mesenchymal stem cell markers in multiple human adult stem cells. Int J Stem Cells. 2014 Nov;7(2):118-26. doi: 10.15283/ijsc.2014.7.2.118. PMID: 25473449; PMCID: PMC4249894.
(4) Arufe MC, De la Fuente A, Fuentes I, de Toro FJ, Blanco FJ. Chondrogenic potential of subpopulations of cells expressing mesenchymal stem cell markers derived from human synovial membranes. J Cell Biochem. 2010 Nov 1;111(4):834-45. doi: 10.1002/jcb.22768. PMID: 20665538.
