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 4 publications

(3 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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“…Bhartiya 7 pointed out that by targeting endogenous very small embryonic-like stem cells (VSELs) to restore fertility for cancer patients, one could avoid legal, ethical and safety issues associated with oncofertility. Gracia and Woodruff 8 responded to the concept of VSELs to tackle oncofertility issues and looked forward to ongoing research in the field. The aim of the present article was to provide an update on VSELs research and how these endogenous stem cells in adult ovary and testis could be targeted to restore fertility of cancer survivors.…”

Section: An Introduction To Oncofertilitymentioning

confidence: 99%

Stem cells survive oncotherapy & can regenerate non-functional gonads

Bhartiya¹

2018

Indian Journal of Medical Research

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A large proportion of patients who survive cancer are rendered infertile as an unwanted side effect of oncotherapy. Currently accepted approaches for fertility preservation involve banking eggs/sperm/embryos or ovarian/testicular tissue before oncotherapy for future use. Such approaches are invasive, expensive, technically challenging and depend on assisted reproductive technologies (ART). Establishing a gonadal tissue bank (for cancer patients) is also fraught with ethical, legal and safety issues. Most importantly, patients who find it difficult to meet expenses towards cancer treatment will find it difficult to meet expenses towards gonadal tissue banking and ART to achieve parenthood later on. In this review an alternative strategy to regenerate non-functional gonads in cancer survivors by targeting endogenous stem cells that survive oncotherapy is discussed. A novel population of pluripotent stem cells termed very small embryonic-like stem cells (VSELs), developmentally equivalent to late migratory primordial germ cells, exists in adult gonads and survives oncotherapy due to their quiescent nature. However, the stem-cell niche gets compromised by oncotherapy. Transplanting niche cells (Sertoli or mesenchymal cells) can regenerate the non-functional gonads. This approach is safe, has resulted in the birth of fertile offspring in mice and could restore gonadal function early in life to support proper growth and later serve as a source of gametes. This newly emerging understanding on stem cells biology can obviate the need to bank gonadal tissue and fertility may also be restored in existing cancer survivors who were earlier deprived of gonadal tissue banking before oncotherapy.

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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 4 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 survive oncotherapy & can regenerate non-functional gonads

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