PMID- 33761993 OWN - NLM STAT- MEDLINE DCOM- 20210708 LR - 20210708 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 12 IP - 1 DP - 2021 Mar 24 TI - The combination of G-CSF and AMD3100 mobilizes bone marrow-derived stem cells to protect against cisplatin-induced acute kidney injury in mice. PG - 209 LID - 10.1186/s13287-021-02268-y [doi] LID - 209 AB - BACKGROUND: Several studies have confirmed that mobilizing bone marrow-derived stem cells (BMSCs) ameliorates renal function loss following cisplatin-induced acute kidney injury (AKI). The aim of this study was to explore whether the combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor (AMD3100) exerts beneficial effects on renal function recovery in a model of cisplatin-induced nephrotoxicity. METHODS: C57BL/6J mice received intraperitoneal injections of G-CSF (200 mug/kg/day) for 5 consecutive days. On the day of the last injection, the mice received a single subcutaneous dose of AMD3100 (5 mg/kg) 1 h before cisplatin 20 mg/kg injection. Ninety-six hours after cisplatin injection, the mice were euthanized, and blood and tissue samples were collected to assess renal function and tissue damage. Cell mobilization was assessed by flow cytometry (FCM). RESULTS: Mice pretreated with G-CSF/AMD3100 exhibited longer survival and lower serum creatinine and blood urea nitrogen (BUN) levels than mice treated with only G-CSF or saline. Combinatorial G-CSF/AMD3100 treatment attenuated tissue injury and cell death, enhanced cell regeneration, and mobilized a higher number of stem cells in the peripheral blood than G-CSF or saline treatment. Furthermore, the mRNA expression of proinflammatory factors was lower, whereas that of anti-inflammatory factors was higher, in the G-CSF/AMD3100 group than in the G-CSF or saline group (all P < 0.05). CONCLUSIONS: These results suggest that combinatorial G-CSF/AMD3100 therapy mobilizes BMSCs to accelerate improvements in renal functions and prevent cisplatin-induced renal tubular injury. This combinatorial therapy may represent a new therapeutic option for the treatment of AKI and should be further investigated in the future. FAU - Chen, Zhi AU - Chen Z AD - Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. FAU - Ren, Xiang AU - Ren X AD - Department of Urology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, 030032, China. AD - Tongji Shanxi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, 030032, China. FAU - Ren, Ruimin AU - Ren R AD - Department of Urology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, 030032, China. AD - Tongji Shanxi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, 030032, China. FAU - Wang, Yonghong AU - Wang Y AD - Tongji Shanxi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, 030032, China. AD - Department of Neurosurgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, 030032, China. FAU - Shang, Jiwen AU - Shang J AD - Tongji Shanxi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, 030032, China. sjw139@126.com. AD - Department of Ambulatory Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, No. 99 Longcheng Street, Taiyuan, 030032, Shanxi, China. sjw139@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210324 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (Benzylamines) RN - 0 (Cyclams) RN - 0 (Heterocyclic Compounds) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - Q20Q21Q62J (Cisplatin) RN - S915P5499N (plerixafor) SB - IM MH - *Acute Kidney Injury/chemically induced/prevention & control MH - Animals MH - Benzylamines MH - Bone Marrow MH - Cisplatin/toxicity MH - Cyclams MH - Granulocyte Colony-Stimulating Factor MH - Hematopoietic Stem Cell Mobilization MH - *Heterocyclic Compounds/pharmacology MH - Mice MH - Mice, Inbred C57BL MH - Stem Cells PMC - PMC7992860 OTO - NOTNLM OT - AMD3100 OT - Acute kidney injury OT - Chemokine OT - Cisplatin nephrotoxicity COIS- The authors declare that they have no competing interests. EDAT- 2021/03/26 06:00 MHDA- 2021/07/09 06:00 PMCR- 2021/03/24 CRDT- 2021/03/25 05:40 PHST- 2021/01/21 00:00 [received] PHST- 2021/03/04 00:00 [accepted] PHST- 2021/03/25 05:40 [entrez] PHST- 2021/03/26 06:00 [pubmed] PHST- 2021/07/09 06:00 [medline] PHST- 2021/03/24 00:00 [pmc-release] AID - 10.1186/s13287-021-02268-y [pii] AID - 2268 [pii] AID - 10.1186/s13287-021-02268-y [doi] PST - epublish SO - Stem Cell Res Ther. 2021 Mar 24;12(1):209. doi: 10.1186/s13287-021-02268-y.