The Role of Stem Cells on the Ovarian Failure Induced by Busulfan in Female Albino Rat

Abstract
Background: Many researches about stem cell therapy in premature ovarian failure treatment have been carried out. The adipose tissue has recently been identified as one of the alternative sources of multipotent resident stem cells in humans. One of the most devastating effects of chemotherapy is the damage of the reproductive system, which in young girls and women younger than 40 years of age is frequently associated with premature ovarian failure. Busulfan has a wide range of using as in a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myeloid leukemia and in patients undergoing bone marrow transplantation.
Aim of the Study: The aim of the study was to evaluate the effect of administration of adipose tissue derived stem cells on the ovarian failure induced by the busulfan in female albino rats.
Material and Methods: 70 female 8 weeks old albino rats were divided into 5 groups. Group I (control Group): They consisted of 20 female albino rats. They were received no treatment and served as untreated control. Group II (adipose tissue derived stem cells treated group): They consisted of 20 female albino rats. They were received adipose tissue derived stem cells (AT-ASCs). They received million and half of million units of AT-ASCs/single dose for each animal I.V. Group III (busulfan treated Group): They consisted of 10 female albino rats. In this group the ovarian failure was induced using busulfan therapy by a dose 2mg for successive 4 days. Group IV (busulfan treated, followed by AT-ASCs treated group): They consisted of 10 female albino rats. In this group the ovarian failure was induced by the same regimen as in group III. After one week of chemotherapeutic treatment, the animals received million and half of million units of AT-ASCs/single dose for each animal I.V. Group V (busulfan treated, followed by AT-AS Cs treated group): They consisted of 10 female albino rats. The rats in this group received the same regimen as group IV but they were sacrificed 4 weeks after the AT-ASCs injection. Biochemical study: Blood samples were taken from all rats from retro-orbital venous plexus and the serum samples were measured for FSH, LH and serum estrogen level using ELISA technique. Paraffin sections for female albino rat ovaries were prepared to be stained with H&E and Masson’s Trichrome stain for Light microscopic study. Specimens of the ovary were also prepared for electron microscopic study.
Results: The AT-ASCs induced definite improvement in the histopathological changes associated with busulfan induced ovarian failure. This improvement was marked one week after AT-ASCs treated but after 4 weeks, there was some regression in this improvement.
Conclusion: AT-ASCs transplantation can improve the ovarian damage induced by the busulfan. The need for second dose of AT-ASCs is suggested.