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Updated: Dec 17, 2025
Author Spotlight: Isolation and Identification of Mesenchymal Stem Cells Derived from Adipose Tissue of Sprague Dawley Rats
Published on: April 7, 2023
Adipose-Derived Mesenchymal Stem Cells and Conditioned Medium Attenuate the Memory Retrieval Impairment During Sepsis
Fariba Akhondzadeh1, Mehri Kadkhodaee1, Behjat Seifi1
1Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, 1417613151, Iran.
Abstract:
In this study, we hypothesized that sepsis induction impairs memory retrieval in rats while transplanted mesenchymal stem cells (MSCs) and MSC-conditioned medium (MSC-CM) application are capable of attenuating those complications. MSCs were obtained from adipose tissue of rats and at the second culture passage; MSCs and MSC-CM were collected. Rats were randomly divided into four experimental groups: sham, CLP, MSC, and MSC-CM. Sepsis was induced by cecal ligation and puncture (CLP) model in the CLP, MSC, and MSC-CM groups. The MSC group received 1 × 106 MSCs/rat (i.p., 2 h after CLP surgery); the MSC-CM rats received the conditioned medium (CM) from 1 × 106 MSCs intraperitoneally 2 h after sepsis induction. Novel object recognition test, sepsis score, and blood pressure measurement were performed 24 h after the treatments. The right hippocampus was taken for western blot analysis. CLP rats showed a significantly higher sepsis score and systolic blood pressure. They also had a significant increase in the phosphorylated form of CAMKII-α, cleaved caspase 3 and Bax/Bcl2 ratio, and a reduction in c-fos protein in the hippocampus tissue samples compared with the sham group. MSC transplantation and MSC-CM administration significantly decreased the mean sepsis score and prevented sepsis-induced attenuation of blood pressure compared with the CLP rats. Animals in the MSC and MSC-CM groups showed a better memory retrieval, attenuation in phosphorylated form of CAMKII-α, cleaved caspase 3 and Bax/Bcl2 ratio, and an increase in c-fos protein expression compared with the CLP group. It seems that CAMKII and c-fos are inversely involved in regulating memory processes in hippocampus. Phosphorylated form of CaMKII-α overexpression may impair the ability of object recognition. Our findings confirmed that MSC-CM application has more advantages compared with transplanted MSCs and may be offered as a promising therapy for inflammatory diseases such as severe sepsis.
Insights
Sepsis impairs memory retrieval, but mesenchymal stem cells (MSCs) and MSC-conditioned medium (MSC-CM) treatments improve memory and reduce sepsis severity in rats. MSC-CM shows greater therapeutic potential.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Sepsis is a life-threatening condition associated with cognitive dysfunction, including memory impairment.
- Mesenchymal stem cells (MSCs) and their conditioned medium (MSC-CM) are being investigated for their therapeutic potential in inflammatory diseases.
Purpose of the Study:
- To investigate the effects of sepsis on memory retrieval in rats.
- To evaluate the therapeutic efficacy of transplanted MSCs and MSC-CM in mitigating sepsis-induced memory deficits and other complications.
Main Methods:
- Sepsis was induced using the cecal ligation and puncture (CLP) model in rats.
- Experimental groups included sham, CLP, MSC treatment, and MSC-CM treatment.
- Memory retrieval was assessed using the novel object recognition test, alongside sepsis scoring, blood pressure measurement, and hippocampal protein analysis (Western blot).
Main Results:
- CLP rats exhibited increased sepsis scores, elevated blood pressure, and hippocampal alterations (increased p-CAMKII-α, cleaved caspase 3, Bax/Bcl2 ratio; decreased c-fos).
- Both MSC and MSC-CM treatments significantly reduced sepsis severity, stabilized blood pressure, and improved memory retrieval compared to CLP rats.
- MSC-CM demonstrated a more advantageous therapeutic effect compared to MSC transplantation.
Conclusions:
- Sepsis induction impairs memory retrieval in rats, partly mediated by hippocampal CAMKII and c-fos pathways.
- MSC transplantation and MSC-CM administration effectively attenuate sepsis-induced memory deficits and systemic complications.
- MSC-CM presents a promising cell-free therapeutic strategy for managing severe sepsis and its neurological sequelae.
