Recovery of Fertility in Azoospermia Rats after Injection of Adipose-Tissue-Derived Mesenchymal Stem Cells: The Sperm Generation

Abstract

The recent reports on the treatment of azoospermia patients, in which spermatozoa could not be traced in their testes, are focused more on the potential use of adult stem cells, like mesenchymal stem cells (MSCs). The aim of this study was to demonstrate the potential use of MSCs derived from adipose tissue in the treatment of azoospermia using rat disease models. After busulfan application, the rats (n = 20) were injected with the GFP+ MSCs into left rete testes. After 12 weeks, the testes with cell injection (right testes) were compared to control (left testes) after dimensional and immunohistochemical analyses. Testes treated with MSCs appeared morphologically normal, but they were atrophic in rats without stem cell treatment, in which the seminiferous tubules were empty. Spermatogenesis was detected, not in every but in some tubules of cell-treated testes. GFP+/VASA+ and GFP+/SCP1+ cells in testes indicated the transdifferentiation of MSCs into spermatogenetic cells in the appropriate microenvironment. Rats with cell treatment were mated to show the full recovery of spermatogenesis, and continuous generations were obtained. The expression of GFP was detected in the mesenchymal stem cells derived from adipose tissue and bone marrow and also in the sperms of offspring. In conclusion, MSCs might be studied for the same purpose in humans in future.

Effect of Stem Cell Therapy on Gentamicin Induced Testicular Dysfunction in Rats

“…As regard to the testicular tissue testosterone, the levels returned to control values with stem cell therapy in gentamicin injected group while estradiol levels returned nearly to control values with stem cell therapy only at the 10 th week of gentamicin injection. These results are in agreement with Cakici et al [47] who reported that treatment of male infertility and testosterone deficiency was possible by adult stem cells. In accordance with our results also, Wu et al [48] reported that MSCs from human bone marrow are able to differentiate into steroidogenic or testicular Leydig cells in vitro.…”

The potential role of mesenchymal stem cells in a hypoxia model induced by sodium nitrite in testes of male albino rats

“…These results are in agreement with Cakici et al (2013) (Cakici et al, 2013), who recorded that MSCs were present in both the external basal partitions and in the internal side of seminiferous tubules. Such observations suggest that MSCs might possess a role in recovering spermatogenesis via two mechanisms: 1) MSC transformation into sperm, or 2) preservation of the spermatogonial cells.…”

The effects of adipose tissue-derived mesenchymal stem cell transplantation during the acute and subacute phases following spinal cord injury

“…rAT-MSCs were isolated and cultured as described previously (4). Briefly, rats (n=6) were anesthetized by injection of 10 mg/kg xylazine and 75 mg/kg ketamine.…”

“…To confirm the phenotypic characteristics of the isolated cells, undifferentiated MSCs were first subjected to flow cytometric analysis using a FACSCalibur (BD Biosciences, San Jose, CA). The analysis was performed against the following antigens: CD29, CD45, CD54, CD90, and CD106 (BD Biosciences) as described previously (4). The in vitro studies of adipogenic, osteogenic, and neurogenic differentiations were performed according to the methods described previously (4).…”

“…Similarly, rat adipose tissue-derived mesenchymal stem cells (rAT-MSCs) were shown to express the early neurogenic markers GFAP, Nestin and c-Fos, indicating that the steps toward neurogenic differentiation occurred in chemical cocktail-supplemented media (4). Therefore, rAT-MSCs and rBM-MSCs have the potential to support the regeneration process directly or indirectly.…”