Therapeutic role of bone marrow-derived mesenchymal stem cells in cyclophosphamide-induced cardiotoxicity in adult male albino rat: a morphological and immunohistochemical study

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Abstract

Introduction

Cyclophosphamide (CP) is a cytotoxic alkylating agent that is extensively used for the treatment of hematological malignances and a variety of solid tumors. Despite its wide spectrum of clinical uses, CP is known to cause multiple organ toxicity.

Aim

This study was carried out to assess the therapeutic role of bone marrow-derived mesenchymal stem cells (MSCs) in ameliorating CP-induced morphological and biochemical cardiotoxicity.

Materials and methods

Adult albino rats weighing 200–230 g were allocated into four groups: group I received no manipulation; group II received a single dose of CP (200 mg/kg body weight) intraperitoneally on day 1 and were sacrificed on day 10; group III (recovery) underwent the same treatment as group II but were sacrificed on day 40; group IV received the same treatment as group II followed by a single MSCs injection (1×106) on day 10 and were sacrificed on day 40.

Results

Creatine phosphokinase serum level increased 10 days after CP administration and then decreased to almost normal following MSC treatment, but not in the recovery group. Histological changes following CP administration, such as distortion of myocardial architecture, ballooning, rarefaction and vacuolation of the sarcoplasm, nuclear changes, inflammatory exudate and cellular infiltration, as well as congested blood capillaries, were encountered. Collagen fibers significantly increased following CP administration and remained high in the recovery group, but their number was markedly decreased following MSCs treatment. Apoptotic bodies were confirmed by immunohistochemical reaction of bax (proapoptotic) and by the cardiac tissue level of bax gene, which showed marked increase in CP-treated and recovery groups but a decrease in the MSCs-treated group. In contrast, bcl-2 reaction (antiapoptotic) and the glutathione peroxidase gene were markedly decreased in the CP-treated and recovery groups but increased in the MSCs-treated group.

Conclusion

It could be concluded that MSCs have a therapeutic role in ameliorating the adverse histological and biochemical effects of CP-induced cardiotoxicity in rats.

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