(W1160) Deciphering the Regenerative Capacities of UC-MSCs and BM-MSCs: A Focus on Cytokine and Fibrosis-Related miRNA Profiles

Abstract: Mesenchymal stem cells (MSCs) are powerful mediators of tissue repair through multipotent differentiation, immunomodulation and paracrine signaling. Their therapeutic efficacy varies by tissue origin. Umbilical cord-derived MSCs (UC-MSCs) offer non-invasive accessibility, faster proliferation, and immunological naïveté, making them promising alternatives to bone marrow-derived MSCs (BM-MSCs). However, their molecular and functional roles in fibrosis regulation remain unclear. This study compares their cytokine secretion and fibrosis-associated miRNA profiles—two key determinants of MSC-mediated regeneration.
To achieve this, UC-MSCs and BM-MSCs were compared via cytokine profiling (antibody array) to quantify secreted factors and miRNA analysis via qPCR-based fibrosis miRNA panels. Fibrotic and antifibrotic miRNAs scored as -1 (fibrotic) or +1 (antifibrotic). A scratch wound closure assay assessed migratory potential, measuring wound coverage at multiple time points.
Using a high-sensitivity cytokine array, UC-MSCs exhibited higher levels of IL-8 (5.33-fold), BDNF (3.16-fold), TIMP-1 (1.40-fold), and TIMP-2 (1.98-fold), suggesting enhanced matrix remodeling and fibrosis regulation. Additionally, ENA-78, Gro α/β/γ, and Gro-α associated with inflammatory and fibrotic responses—were highly expressed in UC-MSCs but at low levels in BM-MSCs. In contrast, BM-MSCs exhibited higher levels of SDF-1α, VEGF-α, IGFBP-2, IGFBP-3, and IGFBP-4, indicating a more pronounced role in angiogenesis rather than fibrosis resolution.
Fibrosis-related miRNA profiling revealed a 318-fold higher anti-fibrotic miRNA score in UC-MSCs compared to BM-MSCs, underscoring their potential in fibrosis resolution. Ongoing analyses aim to correlate cytokine secretion with miRNA expression patterns. Functionally, UC-MSCs exhibited superior migration, covering 71.29% of the wound area within 24 hours, whereas BM-MSCs required 32 hours to reach 65.28% closure.
These study suggests that UC-MSCs posssess enhanced wound healing potential, likely driven by their distinct cytokine and miRNA profiles. The differences in regenerative and anti-fibrotic properties between UC-MSCs and BM-MSCs highlight UC-MSCs as a more promising candidate for cell-based therapies targeting fibrotic diseases.

Funding Source: This study is funded by TUSEB-2022-B-03-27707

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