Abstract

BackgroundSome adult stem cells persist in adult tissue; however, we do not know how to stimulate stem cells in adults to heal injuries. Liver growth factor (LGF) is a biliprotein with hepatic mitogen activity. Its concentration increases markedly in the presence of any type of liver injury, and it shows in vivo therapeutic biological activity at extrahepatic sites.MethodsWe have analyzed the effect of LGF on the replenishment of germinal cells in the testes of mice injected with busulfan, a common cancer drug that also specifically affects germ line stem cells and spermatogonia. We determined the testicular and epididymal weight, spermatozoal concentration in the epididymis and sperm motility, and performed a histological analysis.ResultsIntraperitoneal administration of LGF was able to partially restore spermatogenesis, as well as sperm production and motility, in mice sterilized with busulfan. LGF treatment in busulfan-treated animals that have suffered a disruption of spermatogenesis can accelerate the reactivation of this process in most of the tubules, as shown in the histological analysis.ConclusionsOur results suggest a potential use of LGF in the mobilization of testicular stem cells and in the restoration of spermatogenesis after busulfan-induced damage to the testicular germinal epithelium.

Highlights

  • Some adult stem cells persist in adult tissue; we do not know how to stimulate stem cells in adults to heal injuries

  • We have studied the effects of the administration of Liver growth factor (LGF) on testicular regeneration in mice previously treated with busulfan

  • We have previously demonstrated that CD-1 mice treated with two doses of 40 mg/kg of busulfan remain sterile 70 days after the administration of the drug

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Summary

Introduction

Some adult stem cells persist in adult tissue; we do not know how to stimulate stem cells in adults to heal injuries. Liver growth factor (LGF) is a biliprotein with hepatic mitogen activity. Its concentration increases markedly in the presence of any type of liver injury, and it shows in vivo therapeutic biological activity at extrahepatic sites. Liver growth factor (LGF) is an albumin-bilirubin complex purified from both rat serum and from patients with hepatobiliary disorders [1]. It has been demonstrated that LGF stimulates cell proliferation with no signs of toxicity or tissue degeneration [2]. LGF is used in some experimental models of hypertension, fibrotic lung disease and Parkinson’s disease, showing its potential as an antifibrotic, antihypertensive and neuroregenerative agent [3,4,5]. That study, performed in the rat model, concluded that LGF seems to stimulate

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