Urine-derived stem cells from patients alleviate lupus nephritis via regulating macrophage polarization in a...

Mesenchymal stem cells (MSC) exhibit hopeful therapeutic potential for the treatment of lupus nephritis (LN). Nevertheless, most MSC are harvested invasively and only transplantation of allogeneic MSC takes effect. Urine-derived stem cells (USC) can be obtained by noninvasive and safe access. Whether USC can be used for autologous stem cell transplantation to treat LN remains unknown.

USC were harvested from healthy individuals, systemic lupus erythematosus (SLE) patients with no LN (NLN) and LN patients. The biological characteristics and immunomodulatory ability of three USC types were compared. Therapeutic value of USC for LN in MRL/lpr mice and influence of USC on macrophages were assessed. We further explored the mechanism of USC from LN patients (LN-USC) on macrophage polarization.

LN-USC exhibited faster proliferation and less apoptosis, significantly upregulated regulatory T cells (Treg) and downregulated antibody secreting cells (ASC). Importantly, LN-USC showed the best effect on LN in MRL/lpr mice among the three USC types. Additionally, LN-USC markedly downregulated M1 polarization of macrophages when injected into MRL/lpr mice or co-cultured with human acute monocytic leukemia cell (THP1)-derived M0 macrophages. Moreover, the regulative effect on macrophage polarization and therapeutic efficacy on LN were reversed after knocking down C-X-C motif chemokine ligand 14 (CXCL14) of LN-USC.

These results suggested that transplantation of LN-USC alleviated LN in MRL/lpr mice via inhibiting M1 polarization of macrophages in a CXCL14-dependent manner, indicating that USC serve as a prospective candidate for autologous stem cell therapy of LN.