Commonly used mesenchymal stem cell markers and tracking labels: Limitations and challenges

Area of Science:

• Stem Cell Biology
• Regenerative Medicine
• Cellular Therapeutics

Background:

• Mesenchymal stem cells (MSCs) were initially proposed for tissue repair via cellular differentiation.
• Preclinical studies often aimed to prove MSC differentiation as the therapeutic mechanism.
• Standard MSC identification criteria (CD70, CD90, CD105, CD34) have limitations in vivo.

Purpose of the Study:

• To critically evaluate the reliability of commonly used MSC markers and cell tracking techniques.
• To highlight the challenges in interpreting preclinical MSC transplantation studies.

Main Methods:

• Review of existing literature on MSC marker expression and cell tracking methodologies.
• Analysis of the limitations of standard MSC identification markers (CD markers, Stro-1).
• Assessment of the drawbacks of various cell labeling techniques (e.g., β-gal, GFP, DiI, BrdU, EdU).

Main Results:

• Standard MSC markers (CD70, CD90, CD105) are not specific for MSCs in vivo.
• CD34, a proposed negative marker, is expressed in native MSCs, suggesting they are vascular stem cells (VSCs).
• Common cell labeling methods (e.g., β-gal, GFP, DiI, BrdU, EdU) suffer from issues like endogenous activity, transfer, or detection interference.

Conclusions:

• Current MSC identification markers and cell tracking methods present significant challenges for accurate in vivo assessment.
• These limitations complicate the interpretation of MSC differentiation and therapeutic efficacy in preclinical studies.
• Careful consideration of these caveats is essential for designing and interpreting future MSC transplantation research.