Does co-transplantation of mesenchymal and spermatogonial stem cells improve reproductive efficiency and safety in mice?

Kadam, Prashant; Ntemou, Elissavet; Onofre, Jaime; Saen, Dorien Van; Goossens, Ellen

doi:10.1186/s13287-019-1420-9

Cited by 19 publications

(12 citation statements)

References 54 publications

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“…MSC transplantation improved the expression of germ cell markers in the testes and can be proposed as a suitable method for the treatment of infertility. Several possible mechanisms of testicular function restoration during MSC-induced tissue regeneration have been shown: (1) MSCs may be involved in the suppression of antisperm antibodies (ASA) [ 147 ]; (2) MSCs can reduce factors that lead to infertility through reduction of apoptosis [ 127 ]; (3) MSCs can reduce oxidative stress [ 139 ]; (4) MSCs can stimulate testosterone production [ 126 ] with differentiation into Laydig cells [ 148 ]; (5) MSCs can differentiate into target cells [ 133 ]; (6) the transplanted cells secrete growth factors such as bone morphogenetic proteins (BMPs) and transforming growth factor beta (TGF-β), which are male germ cell inducing factors with ability to stimulate restoration of the recipient’s cellular function [ 149 ]; (7) MSCs connect with endogenous cells, restoring the function of damaged cells [ 150 ]; (8) MSCs reverse the glycolysis and glycogenesis imbalance in sperm by regulating Akt/glycogen synthase kinase 3 (GSK3) axis [ 151 ]; and (9) MSCs can alter expression of some spermatogenesis-related miRNAs and their target genes [ 134 ].…”

Section: Msc Therapy In Animal Model Of Azoospermiamentioning

confidence: 99%

Mesenchymal stromal/stem cells and their exosomes for restoration of spermatogenesis in non-obstructive azoospermia: a systemic review

et al. 2021

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Stem cells have been introduced as new promising therapeutic agents in treatment of degenerative diseases because of having high differentiation potential while maintaining the ability to self-replicate and retaining features of their source cells. Among different type of cell therapies, mesenchymal stromal/stem cell (MSC) therapy is being increasingly developed as a new way to treat structural defects that need to be repaired and regenerated. Non-obstructive azoospermia (NOA) is a reproductive disease in men that causes infertility in 10% of infertile men. Based on in vitro studies, MSCs from different tissue sources have been differentiated into germ cells or gamete progenitor cells by simple methods in both male and female. On the other hand, the therapeutic effects of MSCs have been evaluated for the treatment of NOA animal models created by chemical or surgical compounds. The results of these studies confirmed successful allotransplantation or xenotransplantation of MSCs in the seminiferous tubules. As well, it has been reported that exosomes secreted by MSCs are able to induce the process of spermatogenesis in the testes of infertile animal models. Despite numerous advances in the treatment of reproductive diseases in men and women with the help of MSCs or their exosomes, no clinical trial has been terminated on the treatment of NOA. This systematic review attempts to investigate the possibility of MSC therapy for NOA in men.

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Section: Msc Therapy In Animal Model Of Azoospermiamentioning

confidence: 99%

Mesenchymal stromal/stem cells and their exosomes for restoration of spermatogenesis in non-obstructive azoospermia: a systemic review

et al. 2021

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“…On the other hand, the presence of mesenchymal cells in PTCs may also benefit future transplantation purposes as it has been postulated that mesenchymal cells can contribute to the colonization potential of (cultured) human spermatogonial cell fractions. This idea is substantiated by a recent report of Kadam et al [ 66 ], who showed increased efficiency of spermatogonial colonization after co-transplanting mouse SSCs with mouse bone-marrow derived MSCs in a allogeneic transplantation model.…”

Section: Discussionmentioning

confidence: 71%

ITGA6+ Human Testicular Cell Populations Acquire a Mesenchymal Rather than Germ Cell Transcriptional Signature during Long-Term Culture

Struijk

Mulder

Daalen

et al. 2020

IJMS

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Autologous spermatogonial stem cell transplantation is an experimental technique aimed at restoring fertility in infertile men. Although effective in animal models, in vitro propagation of human spermatogonia prior to transplantation has proven to be difficult. A major limiting factor is endogenous somatic testicular cell overgrowth during long-term culture. This makes the culture both inefficient and necessitates highly specific cell sorting strategies in order to enrich cultured germ cell fractions prior to transplantation. Here, we employed RNA-Seq to determine cell type composition in sorted integrin alpha-6 (ITGA6+) primary human testicular cells (n = 4 donors) cultured for up to two months, using differential gene expression and cell deconvolution analyses. Our data and analyses reveal that long-term cultured ITGA6+ testicular cells are composed mainly of cells expressing markers of peritubular myoid cells, (progenitor) Leydig cells, fibroblasts and mesenchymal stromal cells and only a limited percentage of spermatogonial cells as compared to their uncultured counterparts. These findings provide valuable insights into the cell type composition of cultured human ITGA6+ testicular cells during in vitro propagation and may serve as a basis for optimizing future cell sorting strategies as well as optimizing the current human testicular cell culture system for clinical use.

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“…A possible solution was reported in animal studies, where co-transplanting SSCs and TGFβ1-treated mesenchymal stem cells resulted in reproductive efficacy that is as good as using SSCs alone. The authors demonstrated similar reproductive capacity after transplantation of just half the number of SSCs (Kadam, Ntemou, Onofre, Van Saen, & Goossens, 2019). The second promising method is the freezing of testicular tissue for later autotransplantation.…”

Section: Challeng E S and Future Per S Pec Tive Smentioning

confidence: 91%

Male fertility preservation–Methods, indications and challenges

2020

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Over the past two decades, a variety of medical and modern social conditions have been increasingly recognised as potential causes of infertility. Both patients' and caregivers' awareness of fertility preservation (FP) services in the context of medical and nonmedical indications is steadily increasing (Table 1). A dramatic improvement in the survival of patients with cancer, and other medical conditions, has been observed, primarily due to multiple treatment modalities and increased cure rates. Gonadotoxic treatments, such as chemotherapy and radiotherapy, as well as certain surgical procedures, may predispose patients to testicular failure or ejaculatory dysfunction. Cryopreservation of spermatozoa is therefore crucial for future fertility. Banking of frozen donor spermatozoa offers solutions for men with nonobstructive azoospermia and for women without reproductive partners. In rare circumstances, such as catastrophic injury, or the unexpected death of a partner, cryopreservation of epididymal and testicular spermatozoa allows the surviving partners to preserve gametes for future offspring (Alapati et al., 2009; Papa et al., 2008). Along with prolonged survival came an increased demand to preserve normal reproductive function. Apart from medical conditions, the average paternal age in normal healthy men has increased, making 'age sperm banking' more relevant than before (Ventura, Hamilton,-Sutton, 2003). Cryopreservation of spermatozoa is the most efficient approach in the preservation of male fertility and has become one of the essential elements of assisted reproductive technology (ART). In this review, we aim to discuss the diversity and complexity of various indications and methods in the field of FP. The review will discuss both the medically indicated FP, such as cases of malignancies,

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Does co-transplantation of mesenchymal and spermatogonial stem cells improve reproductive efficiency and safety in mice?

Cited by 19 publications

References 54 publications

Mesenchymal stromal/stem cells and their exosomes for restoration of spermatogenesis in non-obstructive azoospermia: a systemic review

Mesenchymal stromal/stem cells and their exosomes for restoration of spermatogenesis in non-obstructive azoospermia: a systemic review

ITGA6+ Human Testicular Cell Populations Acquire a Mesenchymal Rather than Germ Cell Transcriptional Signature during Long-Term Culture

Male fertility preservation–Methods, indications and challenges

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