The debate on MSCs is over; it's time to promote MSC therapy in practice

TIANJIN, China, Feb. 26, 2025 /PRNewswire/ -- The debate on MSCs, mesenchymal stromal cells versus mesenchymal stem cells, continued for more than two decades (since 2006), being the major obstacle for MSCs study and clinical application. The major issue focuses on mesenchymal stem cells could not be approved for clinical application without a thorough test for safety issue (e.g. tumor formation), but all pre-clinical studies proved the MSCs currently prepared and used are safe without the concerns relevant to stem cells, so that they are mesenchymal stromal cells, not stem cells. However, where is the approval?

A recent publication in HELIYON ends the debate. The work presented by Regenerative Medicine Research Center at West China Hospital and Tasly Stem cell Biology Laboratory, "Unveiling Distinctions Between Mesenchymal Stromal Cells and Stem Cells by Single-Cell Transcriptomic Analysis" breaks the momentum of confusion in the development of MSC therapy both fundamentally and practically.

Using advanced single-cell RNA sequencing (scRNA-seq) and pseudotime trajectory analysis, the research group identified that stem cells exhibit robust self-renewal and differentiation capabilities, mesenchymal stromal cells (MSCs) lack the expression of these critical stemness genes. These genes include SOX2, NANOG, POU5F1, SFRP2, DPPA4, SALL4, ZFP42 and MYCN. On the other hand, there are five critical stromal cell functional genes, TMEM119, FBLN5, KCNK2, CLDN11 and DKK1, that are only expressed in the mesenchymal stromal cells, not in stem cells.

The study identified that currently widely used MSCs from different tissues are mesenchymal stromal cells. But, these cells (MSCs) have been long misused as stem cells in many cases. Although the safety issue becomes ignored due to the nature of MSCs, the therapeutic efficacy of these cells has been a big drawback due to the confusion of their mechanism of action. The mechanism of action of stem cells is mediated by their capacity of differentiation to replace the damaged functional cells, but that of stromal cells is medicated by homing and excrete function leading to microenvironmental rejuvenation. Of course, these two different types of cells must be used differently for their differential function in the host.

Therefore, this new breakthrough not only ends the debate on MSCs, but also and importantly, helps reorientating our effort towards effective application of MSCs in clinical practice.

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