Impaired spermatogenesis caused by busulfan is partially ameliorated by treatment with conditioned medium of adipose tissue derived mesenchymal stem cells

Abdollahifar, Mohammad‐Amin; Azad, Nahid; Sani, Maryam Faraji; Raoofi, Amir; Abdi, Shabnam; Aliaghaei, Abbas; Abbaszadeh, Hojjat-Allah; Ebrahimi, Vahid; Fathabadi, Fatemeh Fadaei; Ghanimat, Faezeh; Movahedi, Maryam

doi:10.1080/10520295.2021.1905182

Cited by 6 publications

(2 citation statements)

References 22 publications

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“…In this technique, the soluble components of CM can initiate regenerative signaling pathways without the assistance of cells (7). Previous studies have demonstrated the effectiveness of CM derived from mesenchymal stem cells in alleviating apoptosis and histological abnormalities in ischemic/reperfusion animal models (35) and busulfan-treated mice (10). The protective effects of CM on busulfan-induced testicular damage were investigated and immediately after busulfan injection, CM was injected directly into the testis, which is different from our study where we administered CM through the efferent ducts 2 wk after CP injection (10).…”

Section: Discussionmentioning

confidence: 99%

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The antiapoptotic effects of conditioned medium from bone marrow-derived mesenchymal stromal stem cells on cyclophosphamide-induced testicular damage in rat: An experimental study

Esmailpour,

Madadi,

Baazm

2024

IJRM

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Background: Cyclophosphamide (CP) has some negative effects on the reproductive system. Stem cells and their metabolites are being utilized to enhance fertility after chemotherapy. Objective: This study aimed to investigate the impact of conditioned medium (CM) derived from bone marrow mesenchymal stromal stem cells (BM-MSCs) on the toxic effects of CP on testicles. Materials and Methods: BM-MSCs were isolated, a CM was collected and 25-fold concentrated. 24 male Wistar rats (8 wk, 200–250 gr) were randomly divided into following groups: control, CP, CP+DMEM, CP+CM. CP was given at a single dose of 100 mg/kg. 2 wk after the CP administration, CM was injected into the testicular efferent duct. Sperm parameters, testicular histopathology, and the level of testosterone were analyzed 2 months after treatment. The expression of B-cell lymphoma 2 (Bcl2) and Bcl2-associated X protein (Bax) genes were evaluated by real-time polymerase chain reaction. Results: CP had a negative effect on testis histology (p < 0.001) and sperm quality (p < 0.001). It changed the expression of genes associated with apoptosis (p < 0.001). Treatment with CM reduced the expression of Bax (p < 0.001), while significantly increasing the expression of Bcl2 (p = 0.01). It improved sperm count (p = 0.03), viability (p < 0.001), motility (p < 0.001), spermatogonial count (p < 0.001), and epithelial thickness of testicular tubules (p = 0.02). Conclusion: These findings suggest that CM produced from BM-MSCs may be valuable for therapeutic approaches in reproductive medicine and may lessen the side effects of CP. Key words: Bone marrow mesenchymal stem cells, Cyclophosphamide, Conditioned medium, Apoptosis, Spermatogenesis.

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Section: Discussionmentioning

confidence: 99%

“…Therefore, BM-MSCs CM, which contains the secreted products of BM-MSC, can serve as an alternative approach to cell therapy (8). CM derived from BM-MSCs has been shown to minimize spermatogonial stem cell apoptosis, increase intercellular adhesion molecule expression (9), and restore spermatogenesis in mice treated with busulfan (10).…”

Section: Introductionmentioning

confidence: 99%

The antiapoptotic effects of conditioned medium from bone marrow-derived mesenchymal stromal stem cells on cyclophosphamide-induced testicular damage in rat: An experimental study

Esmailpour,

Madadi,

Baazm

2024

IJRM

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Ameliorating effects of selenium nanoparticle coated by gallic acid on histological and biochemical parameters of testis in azoospermic rat model

Vatanpour,

Ebrahimzadeh-bideskan,

Rajabian

et al. 2024

Tissue and Cell

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The effects of Wharton’s jelly MSCs secretomes for restoring busulfan-induced reproductive toxicity in male mice

Bahmyari,

Alaee,

Khodabandeh

et al. 2024

Hum Exp Toxicol

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Several studies investigated the application of Mesenchymal stem cells (MSCs) for treating spermatogenic disorders. Considering the limitation of MSC application, the present study aimed to compare Wharton’s jelly MSCs secretomes, including condition medium (CM) 10-fold concentrated (CM10), 20-fold concentrated CM (CM20), and extracellular vesicles (EVs) to restore busulfan-induced damage on male mice reproduction. So, Wharton’s jelly MSCs were cultured, CM was collected, and EVs were isolated. Seventy-two mice were randomly assigned to nine groups, including Control, Busulfan 1 month (1M), Busulfan 2 months (2M), CM10, Busulfan + CM10, CM20, Busulfan + CM20, EVs, and Busulfan + EVs groups. Sperm characteristics, DNA maturity, DNA fragmentation index (DFI), and testicular gene expression were evaluated. Data analysis revealed that CM10 significantly improved sperm plasma membrane integrity, sperm DNA maturity, and DFI in the Busulfan + CM10 group compared to the Busulfan 2M group. Although CM20 and EVs showed a non-significant improvement. Gene expression analysis showed busulfan administration significantly decreased the expression of AR, CREB1, and PLCζ genes, while CM10 significantly restored CREB1 gene expression. The present study demonstrated that CM10 is more effective than CM20 or EVs in reducing busulfan-induced reproductive toxicity.

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Impaired spermatogenesis caused by busulfan is partially ameliorated by treatment with conditioned medium of adipose tissue derived mesenchymal stem cells

Cited by 6 publications

References 22 publications

The antiapoptotic effects of conditioned medium from bone marrow-derived mesenchymal stromal stem cells on cyclophosphamide-induced testicular damage in rat: An experimental study

The antiapoptotic effects of conditioned medium from bone marrow-derived mesenchymal stromal stem cells on cyclophosphamide-induced testicular damage in rat: An experimental study

Ameliorating effects of selenium nanoparticle coated by gallic acid on histological and biochemical parameters of testis in azoospermic rat model

The effects of Wharton’s jelly MSCs secretomes for restoring busulfan-induced reproductive toxicity in male mice

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