Trial evaluation of bone marrow derived mesenchymal stem cells (MSCs) transplantation in revival of spermatogenesis in testicular torsion

Sabbaghi, Mohammad A.; Bahrami, Ahmad Reza; Feizzade, Behzad; Kalantar, Seyed Mehdi; Matin, Maryam Moghaddam; Kalantari, Mahmoud Reza; Aflatoonian, Abbas; Saeinasab, Morvarid

doi:10.1016/j.mefs.2012.06.001

Cited by 22 publications

(14 citation statements)

References 35 publications

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“…Furthermore, intra-seminiferous tubule injection (ZAHKOOK et al, 2014;ZHANG et al, 2014) and intra-testicular injection of BM-MSCs (MONSEFI et al, 2013) were also found to induce spermatogenesis in the seminiferous tubules of busulfan-induced azoospermic rats. Furthermore, the same results with BM-MSCs therapy were found in a testicular torsion model of azoospermia in rats (SABBAGHI et al, 2012). On the other hand, in rats, treatment of busulfan-induced infertile rats with adipose tissue derived MSCs was also demonstrated to lead to morphologically normal spermatogenesis (CAKICI et al, 2013;MEHRABANI et al, 2015b).…”

Section: Discussionmentioning

confidence: 66%

Induction of spermatogenesis after stem cell therapy of azoospermic guinea pigs

et al. 2017

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Bone marrow-derived mesenchymal stem cells (BM-MSCs) provide a large quantitative alternative source for regenerative medicine. This study was undertaken to determine the effect of BM-MSCs in the treatment of busulfan-induced azoospermia in guinea pigs. BM-MSCs were isolated from the femur bones of 6 adult guinea pigs as the donor group, and characterized by morphology, MSC markers and osteogenic and adipogenic differentiation. A dose of 40 mg/kg of busulfan was administered at a 21 day interval to induce azoospermia in 6 guinea pigs. Thirty-five days after the second injection of busulfan, transplantation of 1×10 6 BM-MSCs was performed into the seminiferous tubules of the left testes. The right testis was considered as the positive busulfan treated control. The testes of the donor group were applied as an intact normal control. Then, 60 days after cell therapy, histopathological and histomorphometric evaluations of the testes were performed. The seminiferous tubules treated with BM-MSCs, similar to the intact group, showed a normal appearance of spermatogenesis in comparison to the busulfan-induced azoospermic testes. In conclusion, BM-MSCs were effective in the treatment of azoospermia in a guinea pig model where they restore the fertility of busulfaninduced azoospermic animals after transplantation of BM-MSCs. Therefore, this report could open a window in future to the possibility of BM-MSCs transplantation in the treatment of azoospermia in humans, but more studies should be undertaken for further verification.

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Section: Discussionmentioning

confidence: 66%

Induction of spermatogenesis after stem cell therapy of azoospermic guinea pigs

et al. 2017

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“…Similarly, Aziz et al [48] also reported that bone marrow-derived MSCs when transplanted into the rete testis of busulphan-treated azoospermic rats transdifferentiate into spermatids and spermatocytes. Sabbaghi et al [49] studied the ability of BM derived MSCs in revival of sperm in rat model for testicular torsion. They have reported that transplantation of MSCs via rete testis can revive spermatogenesis.…”

Section: Pluripotent Stem Cells In Adult Body Tissuesmentioning

confidence: 99%

Are Mesenchymal Cells Indeed Pluripotent Stem Cells or Just Stromal Cells? OCT-4 and VSELs Biology Has Led to Better Understanding

Bhartiya

2013

Stem Cells International

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Stem cells have excited researchers because of their potential to regenerate. However, which stem cells will be the best candidate for regenerative medicine remains an enigma. Compared to pluripotent stem cells with associated risks of immune rejection and teratoma formation, adult stem cells especially the mesenchymal stem cells (MSCs) are hyped to be a suitable alternate since they also exhibit pluripotent properties. This review shows that there is a subpopulation of pluripotent very small embryonic-like stem cells (VSELs) among MSCs culture. The two populations differ from each other in expression pattern of OCT-4. VSELs exhibit nuclear OCT-4A, whereas the MSCs have cytoplasmic OCT-4B, similar to our earlier findings in testis and ovary. Pluripotent VSELs with nuclear OCT-4A exist in various adult body organs, and the immediate progenitors express cytoplasmic OCT-4B which is eventually lost as the cell differentiates further. To conclude it is essential to discriminate between nuclear and cytoplasmic OCT-4 expression and also to acknowledge the presence of VSELs.

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“…Lack of differentiation observed by Lasselle suggests the critical requirement for other bone marrow stem cells like mesenchymal cells for restoration of niche and spermatogenesis. Similarly Sabbaghi et al [73] on transplanting mesenchymal cells intra-tubularly, neither observed expression of cKit (crucial spermatogonial marker essential for spermatogenesis), nor spermatogenesis. Unlike above mentioned studies that favor trans-differentiation, our study and an earlier study [36] clearly show that the recovery of spermatogenesis is from the endogenous cells.…”

Section: Discussionmentioning

confidence: 93%

“…In male mice, ability of bone marrow cells to form germ cells [69] is also controversial. Some reports have shown the transdifferentiation potential of bone marrow cells into germ cells [70][71][72][73][74]. Lue et al [71] reported that bone marrow stem cells can differentiate into germ cells after transplantation in mouse testis.…”

Section: Discussionmentioning

confidence: 99%

Very Small Embryonic-Like Stem Cells Survive and Restore Spermatogenesis after Busulphan Treatment in Mouse Testis

An¹,

Bhartiya²,

Sriraman³

et al. 2014

J Stem Cell Res Ther

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Study Objectives: Adult mammalian testes harbor a novel population of quiescent, pluripotent, very small embryonic-like stem cells (VSELs) along with spermatogonial stem cells (SSCs). Present study was undertaken to (i) characterize testicular VSELs (ii) investigate differential effect of chemotherapy on VSELs and SSCs and (iii) to restore the differentiation ability of surviving VSELs by providing healthy somatic microenvironment.Methods: Effect of busulphan (25 mg/Kg) was studied on mouse testes. Syngenic Sertoli cells (10 5 cells per testis) and bone marrow derived mesenchymal cells (10 4 cells per testis) were transplanted separately through intertubular route. Effect of niche reconstruction was studied two months later by histology and immuno-localization of germ cell markers MVH and PCNA. Caudal sperm were evaluated for their ability to fertilize oocytes in vitro.Results: VSELs were 2-6 µm in size, SCA-1 + /CD45 -/LIN -, had high nucleo-cytoplasmic ratio and comprised 0.03% of testicular cells whereas SSC specific marker GFRa localized on a distinct, larger cell population. Busulphan selectively destroyed SSCs and other germ cells however, nuclear OCT-4A, Nanog, Sox-2 and SCA-1 positive VSELs (0.06%) survived. Persisting VSELs were unable to differentiate possibly because chemotherapy also affected the 'niche' comprising Sertoli cells. Complete restoration of spermatogenesis was observed two months post transplantation of Sertoli and mesenchymal cells. Transplanted cells formed neo-tubules in the vicinity of surviving tubules and were possibly a source of growth factors essential for VSELs proliferation and differentiation. Both MVH and PCNA showed increased staining in the transplanted group. qRT-PCR studies revealed existence of a meiotic block in busulphan treated testis which was overcome after transplantation. Resulting sperm progressed to epididymis, showed normal motility and ability to fertilize in vitro. Conclusion:Results show that VSELs survive chemotherapy and can restore spermatogenesis in germ cells depleted mice. Results have direct relevance to address fertility issues of cancer survivors.

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Trial evaluation of bone marrow derived mesenchymal stem cells (MSCs) transplantation in revival of spermatogenesis in testicular torsion

Cited by 22 publications

References 35 publications

Induction of spermatogenesis after stem cell therapy of azoospermic guinea pigs

Induction of spermatogenesis after stem cell therapy of azoospermic guinea pigs

Are Mesenchymal Cells Indeed Pluripotent Stem Cells or Just Stromal Cells? OCT-4 and VSELs Biology Has Led to Better Understanding

Very Small Embryonic-Like Stem Cells Survive and Restore Spermatogenesis after Busulphan Treatment in Mouse Testis

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