Urine-Derived Stem Cells from Patients Reduce Lupus Nephritis in Mice by Modulating Macrophages

A study published in Life Sciences investigates whether urine-derived stem cells (USCs), collected from patients with lupus nephritis (LN), can be used for autologous transplantation — offering a noninvasive alternative to traditional mesenchymal stem cell (MSC) therapies.

Most MSC-based interventions for lupus nephritis rely on allogeneic cells and are sourced via invasive methods. In contrast, USCs are accessible through urine collection, offering a safer and simpler cell source. The researchers compared USCs obtained from healthy donors, systemic lupus erythematosus (SLE) patients without nephritis (NLN), and SLE patients with nephritis (LN).

USCs from LN patients (LN-USC) showed faster growth and lower rates of apoptosis than those from the other two groups. These LN-USCs also significantly influenced immune regulation — increasing regulatory T cells (Tregs), reducing antibody-secreting cells, and showing the most effective disease attenuation in MRL/lpr mouse models of lupus nephritis.

The therapeutic effect appeared linked to changes in macrophage polarization. LN-USCs suppressed M1 macrophage polarization, both in vivo and in co-culture with THP1-derived macrophages. Crucially, these immunomodulatory effects were lost when the chemokine CXCL14 was knocked down in LN-USCs, pointing to its essential role in the process.

The study concludes that LN-USCs may be viable for autologous treatment of lupus nephritis, acting through a CXCL14-dependent inhibition of pro-inflammatory macrophages. These findings offer further insights into immune cell dynamics and raise new questions about how patient-derived cells might shape future autoimmune therapies.