The Effect of Bone Marrow Derived Mesenchymal Stem Cells Versus their Exosomes on Imiquimod-Induced Psoriasis-Like Skin Inflammation in Female Albino Rats: A Histological Study

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Abstract
Introduction: Psoriasis is a chronic skin inflammatory disease. Bone marrow mesenchymal stem cells (BM-MSCs) and their derived exosomes are known for their immunomodulatory properties.Aim of the Work: To investigate the effect of locally injected BM-MSCs and their derived exosomes in female albino rats subjected to imiquimod (IMQ)-induced psoriasis-like skin inflammation.Materials and Methods: Fifty albino rats (40 females and 10 males) were used. The female animals were randomly classified into four groups; group I (control group), group II (IMQ group) where the rats received topical IMQ once daily for 5 consecutive days, group III (IMQ + BM-MSCs) where the rats received a dose of 1 million BM-MSCs on the first day only in addition to topical IMQ, and group IV (IMQ + BM-MSCs-derived exosomes) where the rats received purified concentrate of exosomes derived from BM-MSCs in addition to topical IMQ. The 10 male albino rats served as the source of BM-MSCs and their derived exosomes. After 5 days, all animals were sacrificed, and skin specimens were processed for light microscopic studies: H&E and immunohistochemical staining for Proliferating Cell Nuclear Antigen (PCNA) and Y-chromosome identification using Real-time PCR. Morphometric measurements and statistical analysis were done for the mean epidermal thickness, the mean count of PCNA-positive keratinocytes in the epidermis, and the mean area of dermal PCNA-positive reaction.Results: The general observations and microscopic examination of sections obtained from group II rats revealed psoriasis-like skin inflammatory reactions including acanthosis, parakeratosis, and marked inflammatory infiltrate. There was a statistically significant increase in the epidermal thickness and PCNA-positive reactions in group II compared to other groups. Groups III and IV showed significant improvement, however, group III showed almost normal histological structure.Conclusion: BM-MSCs and purified exosomes concentrate were shown to significantly ameliorate psoriasis-like inflammatory changes in the skin of animal models.