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Updated: Aug 18, 2026
Rapid Depletion of Renal Macrophages Using Human CD59/Intermedilysin Cell Ablation Tool
Published on: May 9, 2025
Adoptive transfer of macrophages ameliorates renal fibrosis in mice
Masashi Nishida1, Yasuko Okumura, Shin-Ichiro Fujimoto
1Department of Pediatric Cardiology and Nephrology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan. mnishida@koto.kpu-m.ac.jp
Abstract:
We performed adoptive transfer of bone marrow-derived (BM) macrophages following pharmacological depletion of leukocytes in a mouse model of unilateral ureteral obstruction (UUO). Treatment with cyclophosphamide (CPM) caused marked decrease in the numbers of F4/80-positive interstitial macrophages as well as in peripheral blood leukocyte counts, and adoptive transfer of BM macrophages to CPM-treated mice resulted in significant increase in the numbers of interstitial macrophages both at day 5 and at day 14 after UUO. At day 5 after UUO, no significant change was observed in the degree of renal interstitial fibrosis either by treatment with CPM or with CPM+macrophage. However, at day 14 after UUO, treatment with CPM caused significant increase in the degree of interstitial fibrosis, and adoptive macrophage transfer to these mice attenuated this enhancement in renal fibrosis. Our result suggests the role of infiltrating macrophages on facilitating tissue repair at late stage of UUO.
Insights
Pharmacological depletion of leukocytes followed by bone marrow-derived macrophage transfer in a unilateral ureteral obstruction (UUO) mouse model showed that macrophages aid in renal tissue repair.
Area of Science:
- Nephrology
- Immunology
- Regenerative Medicine
Background:
- Unilateral ureteral obstruction (UUO) is a common model for studying kidney injury and fibrosis.
- Macrophages play a critical role in kidney inflammation and repair processes.
- Understanding the specific roles of different macrophage populations in UUO is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the impact of leukocyte depletion and subsequent bone marrow-derived macrophage (BMDM) adoptive transfer on renal interstitial fibrosis in a mouse model of UUO.
- To determine the role of infiltrating macrophages in tissue repair during the late stages of UUO.
Main Methods:
- Pharmacological depletion of leukocytes using cyclophosphamide (CPM) in mice subjected to UUO.
- Adoptive transfer of BMDMs into CPM-treated, UUO mice.
- Quantification of interstitial macrophages (F4/80-positive) and assessment of renal interstitial fibrosis at days 5 and 14 post-UUO.
Main Results:
- CPM treatment significantly reduced interstitial macrophage numbers and peripheral leukocyte counts.
- Adoptive transfer of BMDMs restored interstitial macrophage numbers at both time points.
- While CPM alone increased fibrosis at day 14, concurrent BMDM transfer attenuated this fibrotic response.
Conclusions:
- Infiltrating macrophages, replenished via adoptive transfer, play a protective role in mitigating renal interstitial fibrosis at the late stage of UUO.
- These findings highlight the therapeutic potential of modulating macrophage populations for kidney tissue repair.
