Use of Very Small Embryonic-Like Stem Cells to Avoid Legal, Ethical, and Safety Issues Associated With Oncofertility—Reply

Gracia, Clarisa R.; Woodruff, Teresa K.

doi:10.1001/jamaoncol.2016.1008

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…Despite the therapeutic potential of a variety of stem cells including NSCs, their availability is extremely limited, mainly due to their individual shortcomings, including low accessibility and expansion and ethical and immune concerns [39]. Although ESCs, iPSCs, and MSCs hold great potential in regenerative medicine, their clinical application could not circumvent the risk for undesired genotoxicity, mutagenesis, and tumorigenesis besides differentiation uncertainty and ethical controversies [9–11, 43]. For this reason, finding a desirable cell-based therapy for PD is essential.…”

Section: Discussionmentioning

confidence: 99%

Generation of functional dopaminergic neurons from human spermatogonial stem cells to rescue parkinsonian phenotypes

et al. 2019

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Background Recent progress in the induced generation of dopaminergic (DA) neurons from different types of stem cells or reprogrammed somatic cells holds tremendous potential for the treatment of Parkinson’s disease (PD). However, the lack of a reliable source for cell replacement therapy remains a major limitation in the treatment of human neurological disorders. Additionally, the current protocols for in vitro differentiation or cell reprogramming to generate human DA neurons are laborious, time-consuming, and expensive, and efficient conversion of human spermatogonial stem cells (hSSCs) to functional DA neurons has not yet been achieved. Methods Primary hSSCs from testicular tissues of patients were exposed to an improved induction system, which consisted mainly of olfactory ensheathing cell conditioned culture medium (OECCM) and a set of defined cell-extrinsic factors and small molecules. Morphological changes were assessed, along with the expression of various DA neuron phenotypic markers (e.g., Tuj-1, TH, Nurr1, DAT) and several critical pro-DA neurogenesis effectors (e.g., EN-1, Pitx3, Foxa2, Lmx1a, Lmx1b, and OTX2). In addition, transcriptome analysis was used to further evaluate the genetic similarity between the artificially differentiated DA neurons and genuine ones. Concomitantly, the functional properties of converted DA neurons including synapse formation, dopamine release, electrophysiological activity, and neuron-specific Ca 2+ signaling images were determined. Finally, hSSCs in the early stage of induction were evaluated for survival, differentiation, migration, tumorigenicity in the mouse striatum, and improvement of functional deficits in MPTP-induced PD animals. Results The hSSC-derived neurons not only acquired neuronal morphological features but also expressed various phenotypic genes and protein characteristic of DA neurons and several effectors critical for pro-DA neurogenesis. Strikingly, as the period of induction was prolonged, expression of the critical molecules for DA neuron epigenetic status gradually increased while hSSC-specific markers sharply decreased. After 3 weeks of induction, the transdifferentiation efficiency reached 21%. In addition, hierarchical clustering analysis showed that the differentiated DA neurons closely resembled genuine ones. Furthermore, the hSSC-derived neurons gained sophisticated functional properties of wild-type DA neurons, and pro-induced hSSCs efficiently survived, migrated, and differentiated into DA neurons without tumorigenesis after transplantation into mouse striatum, leading to improvement of functional deficits in PD animals. Conclusions The results showed that, using the present improved straightforward approach, hSSCs could acquire DA neuron morphological features and functional properties and rescue parkinsonian phenotypes. Our strategy for the conversion of hSSCs into DA neurons is very efficient and thus may p...

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Section: Discussionmentioning

confidence: 99%

Generation of functional dopaminergic neurons from human spermatogonial stem cells to rescue parkinsonian phenotypes

et al. 2019

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“…Being relatively quiescent, VSELs experience asymmetrical cell divisions to become progenitor cells that divide rapidly, expanding clonal offsprings through symmetrical cell divisions. These expanded progenitor cells form cysts, and ultimately differentiate into oocytes in the ovaries [35][36][37][40][41][42][43][44][45]. Such stem/ progenitor cells express follicle-stimulating hormone (FSH) receptors and are activated by FSH.…”

Section: Classification Of Fgscsmentioning

confidence: 99%

Female germline stem cells: aging and anti-aging

Hong

Wang²,

Zhu

et al. 2022

J Ovarian Res

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The delay of ovarian aging and the fertility preservation of cancer patients are the eternal themes in the field of reproductive medicine. Acting as the pacemaker of female physiological aging, ovary is also considered as the principle player of cancer, cardiovascular diseases, cerebrovascular diseases, neurodegenerative diseases and etc. However, its aging mechanism and preventive measures are still unclear. Some researchers attempt to activate endogenous ovarian female germline stem cells (FGSCs) to restore ovarian function, as the most promising approach. FGSCs are stem cells in the adult ovaries that can be infinitely self-renewing and have the potential of committed differention. This review aims to elucidate FGSCs aging mechanism from multiple perspectives such as niches, immune disorder, chronic inflammation and oxidative stress. Therefore, the rebuilding nichs of FGSCs, regulation of immune dysfunction, anti-inflammation and oxidative stress remission are expected to restore or replenish FGSCs, ultimately to delay ovarian aging.

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Stem Cells and Organs-on-chips: New Promising Technologies for Human Infertility Treatment

et al. 2021

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Having biological children remains an unattainable dream for most couples with reproductive failure or gonadal dysgenesis. The combination of stem cells with gene editing technology and organ-on-a-chip models provides unique opportunity for infertile patients with impaired gametogenesis caused by congenital disorders in sex development or cancer survivors. But, how will these technologies overcome human infertility? This review discusses the regenerative mechanisms, applications and advantages of different types of stem cells for restoring gametogenesis in infertile patients, as well as major challenges that must be overcome prior to clinical application. The importance and limitations of in vitro generation of gametes from patient-specific human induced pluripotent stem cells (hiPSCs) will be discussed in the context of human reproduction. The potential role of organ-on-a-chip models that can direct differentiation of hiPSCs-derived primordial germ cell-like cells to gametes and other reproductive organoids is also explored. These rapidly evolving technologies provide future prospects for improving fertility to individuals and couples who experience reproductive failure.

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Use of Very Small Embryonic-Like Stem Cells to Avoid Legal, Ethical, and Safety Issues Associated With Oncofertility—Reply

Cited by 3 publications

References 6 publications

Generation of functional dopaminergic neurons from human spermatogonial stem cells to rescue parkinsonian phenotypes

Generation of functional dopaminergic neurons from human spermatogonial stem cells to rescue parkinsonian phenotypes

Female germline stem cells: aging and anti-aging

Stem Cells and Organs-on-chips: New Promising Technologies for Human Infertility Treatment

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