In May 2025, the International Society for Cell & Gene Therapy (ISCT) released new identification criteria for Mesenchymal Stromal Cells (MSCs), bringing an end to nearly two decades of academic debate over their identity and function. This significant scientific shift not only redefines the fundamental properties of MSCs but also establishes a new framework for the development and quality control of cell therapy products. Compared to the 2006 standard that has been in use until now, the new standard systematically restructures cell definitions, identification criteria, and quality controls. The depth and scope of this reform mark a major milestone in the field of cell therapy.
From "Stem Cells" to "Stromal Cells": Three Key Changes
01 Clarification of Terminology
The most striking change in the new standard is the formal definition of MSCs as "Mesenchymal Stromal Cells" instead of the widely used term "Mesenchymal Stem Cells." This is not a mere semantic adjustment but a reevaluation of the cells’ fundamental nature based on extensive scientific evidence.
According to the new standard, researchers who wish to continue using the term "Mesenchymal Stem Cells" must provide experimental evidence that the cells possess actual stem cell properties—such as self-renewal and multi-lineage differentiation potential. This requirement reflects the scientific community’s strong emphasis on terminological accuracy and aims to resolve longstanding issues of reproducibility caused by naming confusion.
Notably, the two key identification criteria from the 2006 standard—"trilineage differentiation in vitro" (osteogenesis, adipogenesis, and chondrogenesis) and "adherence to plastic under standard conditions"—are no longer mandatory. This adjustment acknowledges the limitations of traditional "stemness" assays in distinguishing true stem cells from more specialized stromal cell populations.
02 Optimization of Identification Criteria
The new standard comprehensively upgrades the identification criteria for MSCs, particularly in the detection of surface markers. It introduces stricter and more detailed requirements:
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Positive Markers: CD73, CD90, and CD105 are still recognized as basic positive markers, but researchers must now specify the threshold percentage for positive identification via flow cytometry.
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Negative Markers: CD45 (a hematopoietic marker) must be included to ensure that the cell population is not contaminated by hematopoietic lineages.
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Reporting Requirements: Researchers must report complete results for each marker, including the percentage of positive cells, to improve data transparency and comparability.
Importantly, the new standard incorporates efficacy and functional characterization into Critical Quality Attributes (CQAs), emphasizing the need to describe these attributes to define the clinical functionality of MSCs. This shift reflects the growing demand for translational research and ensures that MSC products not only meet phenotypic standards but also deliver the expected therapeutic outcomes.
03 New Requirements on Tissue Origin and Quality Attributes
Another major update is the emphasis on specifying the tissue origin of MSCs, acknowledging that cells from different sources may have distinct phenotypic and functional properties. With the development of single-cell omics, it is theoretically possible to isolate MSCs from any tissue (including the brain), but their clinical potential must be independently verified.
In terms of quality control, the new standard proposes more comprehensive requirements:
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Standardization of Culture Conditions: Detailed reporting on medium components, passaging methods, and culture environment parameters is required.
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Safety Testing: Enhanced detection for microbial contamination (e.g., bacteria, fungi, mycoplasma) is mandated.
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Functional Validation: Specific efficacy tests should be designed based on the intended clinical application.
ISCT 2006 vs. 2025 MSC Identification Standards Comparison
| Standard Element | 2006 Standard | 2025 Standard |
|---|---|---|
| Cell Definition | Mesenchymal Stem Cells (MSCs) | Mesenchymal Stromal Cells (MSCs) |
| Stemness Requirement | Must demonstrate trilineage differentiation | Must provide evidence to use the term "stem" |
| Marker Detection | Qualitative (positive/negative) | Quantitative (thresholds and percentages) |
| Tissue Origin | Not emphasized | Must be specified and considered |
| Critical Quality Attributes | Not required | Must assess efficacy and functional properties |
| Culture Conditions | No standard reporting requirement | Detailed parameter reporting required |
What Do These Changes Really Mean?
The clarification of MSC identification standards has important implications for clinical research, particularly in terms of therapeutic potential and regulatory compliance. In simple terms:
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Safer Treatments: With accurate standards, MSCs used for therapy are more consistent in quality, reducing adverse effects—like standardized pharmaceuticals.
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Faster R\&D: Clear, unified standards help researchers avoid unnecessary detours, accelerating drug development and getting new therapies to patients more quickly.
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Deeper Research: Defining the true identity of MSCs allows researchers to pursue more precise studies, understand mechanisms of action, and unlock more therapeutic potential.
For the public, what MSCs are called isn’t the most important thing—safety and efficacy matter most. The new standards reduce the risk of tumorigenesis, enhance therapeutic stability, and support advanced modifications (like iPSC-derived MSCs) for improved outcomes. Engineered MSCs may lower costs, reduce batch variability, and make commercialization more feasible.
YOCON’s Solution
The implementation of the new standards is triggering a value reconstruction across the cell therapy industry. Under stricter standardization and quality demands, the choice of key raw materials like culture media becomes increasingly important.
YOCON Bio, a leading Chinese developer and manufacturer of serum-free media for cell therapy, has been deeply involved in MSC research since 2012. Leveraging decades of experience and countless success stories, YOCON has developed a comprehensive serum-free culture product line for MSCs. These products demonstrate stable batch performance and comparable quality to international brands, supporting large-scale MSC expansion. YOCON is collaborating with several pharmaceutical companies in China and the U.S. for joint cell therapy drug submissions and clinical translation.
YOCON has established a complete GMP quality management system to ensure its media products meet regulatory and clinical research requirements. All products are manufactured in B+/A-grade cleanroom environments, matching the standards of finished product production. Equipment is designed to meet both NMPA (China) and FDA (U.S.) requirements, ensuring product consistency and traceability.
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