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.
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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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SOURCE Tasly