Induced pluripotent stem cells and hematological malignancies: A powerful tool for disease modeling and drug development.

The derivation of human pluripotent stem cell (iPSC) lines by in vitro reprogramming of somatic cells revolutionized research: iPSCs have been used for disease modeling, drug screening and regenerative medicine for many disorders, especially when combined with cutting-edge genome editing technologies. In hematology, malignant transformation is often a multi-step process, that starts with either germline or acquired genetic alteration, followed by progressive acquisition of mutations combined with the selection of one or more pre-existing clones. iPSCs are an excellent model to study the cooperation between different genetic alterations and to test relevant therapeutic drugs. In this review, we will describe the use of iPSCs for pathophysiological studies and drug testing in inherited and acquired hematological malignancies.

[In vitro oogenesis: How far have we come?] / Ovogenèse in vitro : quel chemin parcouru ?

Oogenesis is a complex cellular and molecular process whose fundamental mechanisms are still poorly described or not yet elucidated, especially in human species. The development of an in vitro model of oogenesis, particularly during fetal development in humans, is a critical step that would allow: (i) a better understand of the biological mechanisms of oogenesis; (ii) a refinement of medical diagnosis for women suffering from infertility; and (iii) providing new therapeutics for reproductive pathologies. The genesis of this model could be considered from ES/iPS cells. In this article, we will trace the physiological mechanisms of oogenesis in vivo and discuss the studies carried out in the field of in vitro oogenesis from ES/iPS cells, as well as the challenges to be met in the future.

Assessment of the optimal vitrification protocol for pre-pubertal mice testes leading to successful in vitro production of flagellated spermatozoa.

Testicular tissue cryopreservation offers the hope of preserved future fertility to pre-pubertal boys with cancer before exposition to gonadotoxic treatments. The objective of this study was to compare controlled slow freezing (CSF) with five vitrification techniques for cryopreservation of murine pre-pubertal testicular tissue and to evaluate the best protocol that could provide a successful completion of spermatogenesis after in vitro maturation. Testicular tissue from 24 mice at 6.5 days post-partum (dpp) was used to compare several vitrification protocols with one another, as well as with a CSF protocol. Toxicity test using additional 12 mice was performed for all cryopreservation solutions. Fresh tissue (FT) from six mice was used as a control. Once the optimal vitrification protocol was selected [the modified solid surface vitrification No. 1 (mSSV1 )], testes from 18 mice were cultured in vitro for 30 days with (i) fresh, (ii) slow-frozen/thawed and (iii) vitrified/warmed tissues. Testes from six mice at 36.5 dpp were used as controls. At day 30 of in vitro culture, germ cells of the seminiferous tubules showed a high ability to proliferate and elongated spermatids were observed after both freezing techniques, confirming the successful completion of in vitro spermatogenesis. However, after mSSV1 , the morphological alterations and the percentage of pyknotic seminiferous tubules were lower than CSF (4.67 ± 0.53 vs. 10.1 ± 1.12 and 22.7 ± 2.83% vs. 37.3 ± 4.24% respectively). Moreover, the number of flagellated spermatozoa produced per mg of tissue was higher for mSSV1 than for CSF (35 ± 3 vs. 9 ± 4 cells), with amounts of secreted testosterone during the culture close to those of FT. The mSSV1 protocol resulted in success rates better than CSF in maintaining testicular tissue structure, tubular morphology and tissue functions not solely for immediate frozen/thawed tissues but also after a long-term in vitro culture.

[In vitro spermatogenesis new horizon to restore fertility?]. / Spermatogenèse in vitro nouvel horizon pour restaurer la fertilité ?

The survival of the young boy after cancer has considerably progressed in recent years due to the efficiency of chemo/radiotherapy against the tumor cells. However, this treatment causes adverse effects on healthy tissues, including fertility. Freezing testicular tissue before highly gonadotoxic treatment is a prerequisite for preserving fertility in prepubertal boys that do not produce sperm yet. But which strategy proposes to restore fertility from frozen-thawed testicular tissue? One potential solution would be to consider an in vitro maturation of spermatogonial stem cells. In this article we trace the chronological development of in vitro spermatogenesis that resulted in mouse sperm production in vitro and give an overview of new challenges for the future.

[Male gamete spermatozoon or spermatid?]. / Gamète mâle un spermatozoïde ou une spermatide?

Normal spermatogenesis results from a balance between process of cell proliferation, cell differentiation and apoptosis that concern somatic cells and germ cells. Dysfunction of spermatogenesis may be the result of constitutional or acquired abnormalities of spermatogonia stem cells or somatic cells. To overcome these problems, it seems necessary to implement preventive measures for germ stem cell preservation or substitute measures to replace them, the objective being to replicate in vivo or in vitro the process of spermatozoa production. This article will discuss the different experimental strategies for considering the in vivo or in vitro production of spermatozoa, outside the physiological process.