Making gametes from pluripotent stem cells: embryonic stem cells or very small embryonic-like stem cells?

Bhartiya, Deepa; Anand, Sandhya; Patel, Hiren

doi:10.21037/sci.2016.09.06

Cited by 7 publications

(8 citation statements)

References 38 publications

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“…Current understanding on a role of VSELs/OSCs resulting in neo-oogenesis and follicular assembly was recently reviewed [ 119 , 120 ]. We have reported similar findings in the testis including that testicular niche (Sertoli cells) gets compromised after chemotherapy and transplanting mesenchymal cells restores spermatogenesis [ 26 , 55 ].…”

Section: Making Oocytes In a Dishmentioning

confidence: 74%

“…However, as the initial cells were not purified, it was possible that few mature stem/germ cells including SSCs existed in the initial cultures that could have differentiated into sperm. The approaches of in vitro differentiation of mouse VSELs by our group [ 54 ] and mES cells by Zhou et al [ 44 ] were compared and discussed [ 55 ].…”

Section: Making Sperm In a Dishmentioning

confidence: 99%

“…It becomes crucial to take cognizance of the findings that a novel population of stem cells termed VSELs exist in adult gonads and survive oncotherapy whereas the stem cells niche gets compromised with age and also as a result of oncotherapy. Providing a healthy niche by transplanting mesenchymal cells can regenerate both non-functional testis [ 55 ] and ovary [ 121 ].…”

Section: Making Oocytes In a Dishmentioning

confidence: 99%

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Making gametes from alternate sources of stem cells: past, present and future

Bhartiya

Anand

Patel

et al. 2017

Reprod Biol Endocrinol

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Infertile couples including cancer survivors stand to benefit from gametes differentiated from embryonic or induced pluripotent stem (ES/iPS) cells. It remains challenging to convert human ES/iPS cells into primordial germ-like cells (PGCLCs) en route to obtaining gametes. Considerable success was achieved in 2016 to obtain fertile offspring starting with mouse ES/iPS cells, however the specification of human ES/iPS cells into PGCLCs in vitro is still not achieved. Human ES cells will not yield patient-specific gametes unless and until hES cells are derived by somatic cell nuclear transfer (therapeutic cloning) whereas iPS cells retain the residual epigenetic memory of the somatic cells from which they are derived and also harbor genomic and mitochondrial DNA mutations. Thus, they may not be ideal starting material to produce autologus gametes, especially for aged couples. Pluripotent, very small embryonic-like stem cells (VSELs) have been reported in adult tissues including gonads, are relatively quiescent in nature, survive oncotherapy and can be detected in aged, non-functional gonads. Being developmentally equivalent to PGCs (natural precursors to gametes), VSELs spontaneously differentiate into gametes in vitro. It is also being understood that gonadal stem cells niche is compromised by oncotherapy and with age. Improving the gonadal somatic niche could regenerate non-functional gonads from endogenous VSELs to restore fertility. Niche cells (Sertoli/mesenchymal cells) can be directly transplanted and restore gonadal function by providing paracrine support to endogenous VSELs. This strategy has been successful in several mice studies already and resulted in live birth in a woman with pre-mature ovarian failure.

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Section: Making Oocytes In a Dishmentioning

confidence: 74%

Section: Making Sperm In a Dishmentioning

confidence: 99%

Section: Making Oocytes In a Dishmentioning

confidence: 99%

See 1 more Smart Citation

Making gametes from alternate sources of stem cells: past, present and future

Bhartiya

Anand

Patel

et al. 2017

Reprod Biol Endocrinol

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“…Success was recently achieved to derive mouse gametes and birth of pups 22 . However, the process (rate of pregnancy outcome) remained low and fraught with safety issues possibly due to inappropriate epigenetic reprogramming 22 23 . Deriving human gametes from ES/iPS stem cells is a long way to reach the clinics 24 .…”

Section: Available Options For Fertility Preservation Before Oncothermentioning

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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“…The complexity of the systemic and testicular microenvironment makes it difficult to study SSCs in vivo; SSCs may thus be well studied in an in vitro microenvironment where the investigator can carefully regulate the composition of the microenvironment.The establshment of stable human SSCs in vitro would create a useful stem cell model for studying the proliferation and differentiation of SSCs [Liu et al 2011]. Recently very small embryoniclike stem cells (VSELs) have been identified in the testis, which are more primitive stem cells that can give rise to SSCs in vitro [Bhartiya et al 2016].…”

Section: Introductionmentioning

confidence: 99%

In vitroeffects of melatonin on colonization of neonate mouse spermatogonial stem cells

Navid

Rastegar

Baazm

et al. 2017

Systems Biology in Reproductive Medicine

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We have recently reported that antioxidant supplements enhance the efficacy of cryopreserved spermatogonial stem cells. Melatonin is considered a free radical scavenger which has direct and indirect antioxidant effects in in vitro and in vivo microenvironments. Due to the anti-apoptotic properties of melatonin, researchers have proposed that melatonin may improve the efficiency of spermatogonial stem cell (SSC) transplantation. However, the appropriate methodology which facilitates SSC proliferation remains to be determined. Identification of a proper propagation system is essential for the future application of SSCs in the field of infertility. The aim of the present study was to investigate the effects of melatonin on the colonization of SSCs. SSCs were isolated from the testes of three to six day old mice, and their purities were assessed by cytometry using Plzf antibody. Isolated testicular cells were cultured in the absence or presence of melatonin extract for two weeks. Suppression of differentiation and maintenance of spermatogonial stem cells was confirmed by alkaline phosphatase staining and immunocytochemistry using Plzf antibody. The number and diameter of the colonies of SSCs were assessed during the 7 and 14 days of culture, and the expression of Id4, Plzf, and C-kit were evaluated using real-time PCR at the end of the culture period. The survival rate of the cultured cells in the presence of melatonin was significantly higher than the control group. The number and diameter of colonies also increased in the cells treated with melatonin. The results of our study suggest that culture of SSCs with 100 μM melatonin supplementation can increase SSCs proliferation significantly.

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Making gametes from pluripotent stem cells: embryonic stem cells or very small embryonic-like stem cells?

Cited by 7 publications

References 38 publications

Making gametes from alternate sources of stem cells: past, present and future

Making gametes from alternate sources of stem cells: past, present and future

Stem cells survive oncotherapy & can regenerate non-functional gonads

In vitroeffects of melatonin on colonization of neonate mouse spermatogonial stem cells

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