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Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
[Bone marrow mesenchymal stem cell-derived exosome protects kidney against ischemia reperfusion injury in rats]
Rulin Wang1, Miao Lin1, Liping Li1
1Department of Urology, Fudan University Zhongshan Hospital, Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
Objective:
To explore the protective effects and mechanism of exosomes derived from bone marrow mesenchymal stem cells (BM-MSC) on ischemia reperfusion injury (IRI) in rats.
Methods:
Rat-MSC were isolated, cultured and identified.Exosome was extracted from BM-MSC and observed under transmission electron microscope (TEM). The expression of surface molecular marker CD63 was tested by flow cytometry. Male Sprague-Dawley rats were randomly grouped into sham-operated (Sham), ischemia reperfusion (IR), MSC-treated (IR+MSC), MSC-derived exosome-treated (IR+MSC-ex) and fibroblast-derived exosome-treated (IR+F-ex) groups. The model for ischemia reperfusion injury was constructed. The serum levels of creatinine and blood urea nitrogen (BUN) were tested in each group. The histomorphological changes in of renal tissue samples were examined by hematoxylin and eosin-stained tissue samples. Cellular apoptosis was examined by terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) staining. The expression levels of proinflammatory cytokines interleukin 1β and tumor necrosis factor α were examined by reverse transcription (RT)-PCR. And the expression level of caspase-3 was examined by Western blot.
Results:
Rat BM-MSCs were successfully isolated and cultured. Dectection of surface markers revealed high expression levels of CD29 and CD44 and a low expression level of CD34. MSC differentiated successfully into osteoblasts and lipocytes after growing in osteoblast- and lipocyte-inducing media respectively. Typical appearances of exosome were observed under transmission electron microscope. CD63 was positive on flow cytometry. Compared with the IR group, the IR+MSC and IR+MSC-ex groups showed low levels of serum creatinine and BUN, mild pathological injury, decreased number of apoptotic cells and low expression of inflammatory factors and caspase-3 (IR group, 4 310 ± 616;IR+MSC group, 2 569 ± 530; IR+MSC-ex group, 3 144 ± 343, both P < 0.05).
Conclusion:
Rat BM-MSC-derived exosome protects against ischemia reperfusion injury with decreased inflammatory response and apoptosis in rats.
Insights
Bone marrow mesenchymal stem cell-derived exosomes protect against kidney injury caused by ischemia reperfusion. These exosomes reduce inflammation and cell death, offering a potential therapeutic strategy for this condition.
Area of Science:
- Regenerative Medicine
- Cell Biology
- Nephrology
Background:
- Ischemia reperfusion injury (IRI) is a significant cause of acute kidney injury.
- Mesenchymal stem cells (MSCs) show therapeutic potential, but their exosomes may offer a cell-free alternative.
Purpose of the Study:
- To investigate the protective effects of exosomes derived from bone marrow mesenchymal stem cells (BM-MSC) against IRI in a rat model.
- To elucidate the underlying mechanisms of BM-MSC exosome-mediated protection.
Main Methods:
- Rat BM-MSCs were isolated, cultured, and characterized.
- Exosomes were extracted from BM-MSCs and analyzed via transmission electron microscopy and flow cytometry for CD63 expression.
- Rats underwent IRI, and were treated with MSCs or MSC-derived exosomes.
- Renal function (creatinine, BUN), histopathology, apoptosis (TUNEL), and inflammatory markers (IL-1β, TNF-α, caspase-3) were assessed.
Main Results:
- BM-MSCs were successfully isolated and characterized, and exosomes exhibited typical morphology and CD63 expression.
- Treatment with BM-MSC-derived exosomes significantly reduced serum creatinine and BUN levels compared to the IRI group.
- Exosome treatment led to milder renal histopathological damage, decreased cellular apoptosis, and lower expression of inflammatory cytokines and caspase-3.
Conclusions:
- Exosomes derived from BM-MSCs demonstrate significant protective effects against IRI in rats.
- BM-MSC exosomes mitigate IRI by reducing inflammatory responses and inhibiting apoptosis.
- These findings highlight BM-MSC-derived exosomes as a promising therapeutic agent for IRI.

