Bone Marrow-Derived Mesenchymal Stem Cells Modulate Apoptosis and Angiogenesis in Cyclophosphamide-Induced Spleen Injury in Adult Female Rats

Saad El  Dien, Heba M.; Abdelrahman Bakhaat, Gamal; Rashwan, Eman Kadry; Alaaeldin, Rania; Fathy, Moustafa

doi:10.21608/ejh.2022.152313.1735

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	Bone Marrow-Derived Mesenchymal Stem Cells Modulate Apoptosis and Angiogenesis in Cyclophosphamide-Induced Spleen Injury in Adult Female Rats
Article 3, Volume 46, Issue 4, December 2023, Page 1578-1589 PDF (1.25 MB)
Document Type: Original Article
DOI: 10.21608/ejh.2022.152313.1735
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Authors
Heba M. Saad El dien ¹; Gamal Abdelrahman Bakhaat²; Eman Kadry Rashwan³; Rania Alaaeldin⁴; Moustafa Fathy⁵
¹Department of Histology, Faculty of Medicine, Assuit Univ.
²Department of Anatomy, College of Medicine, Jouf University Al-Azhar University, Faculty of Medicine, Assiut, Egypt
³4Department of Physiology, College of Medicine, Jouf University, Jouf 42421, Saudi Arabia. 5Department of Physiology, Faculty of Medicine, Al-Azhar University, Assiut 71524, Egypt.
⁴Department of Biochemistry, Faculty of Pharmacy, Deraya University, Minia, Egypt.
⁵Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt. Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Abstract
Introduction: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent cells that have been examined for their potential role in cell therapy. BM-MSCs displayed repairing and cytoprotective functions against many injured tissues. Furthermore, they exerted trophic effects mediated by different growth factors and cytokines. For severe spleen-associated diseases, stem cell therapy could be considered for its possible use in targeting and repairing damaged tissues and organs. Therefore, the aim of the present study is to investigate, on molecular basis, the cytoprotective and healing capacity of BM-MSCs in cyclophosphamide (CP)-induced spleen damage in rats. Materials and Methods: A total number of Forty Sprague Dawley adult female rats were divided into two groups: the normal control group (NC) and CP-treated group. Normal control (NC) group that was treated once daily with sterile saline, and a CP-treated group that was injected intraperitoneally by CP at the concentration of 70 mg/kg for three successive days. The latter group was further subdivided into three subgroups: - the (CP-treated group) was sacrificed one week after CP treatment, the (BM-MSCs treated group), in which BM-MSCs were injected by a single dose of Male BM-MSCs 5x106/Kg BW via intraperitoneal injection on the tenth day after CP treatment, and the (CP auto-healing group ) was left without treatment. Spleen was dissected from all animals and prepared for histological examination. The expression of genes and proteins was estimated by real-time qPCR and immunohistochemistry. Results: BM-MSCs restored the normal architecture of the damaged spleen. They regained the mRNA levels of p53, caspase3, bcl2 more/less similar to the normal control group. The expression of VEGF was upregulated after BM-MSCs injection. Also, BM-MSCs relatively retained the normal expression of CD14, CD21, Akt and PI3K proteins after CP-induced toxicity. Conclusion: This study revealed the potential therapeutic role of BM-MSCs in severe damaged spleen and explained the underlying mechanism on molecular basis.
Keywords
Angiogenesis; apoptosis; cyclophosphamide; MSCs; spleen


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