Endogenous, very small embryonic-like stem cells: critical review, therapeutic potential and a look ahead

Bhartiya, Deepa; Shaikh, Ambreen; Anand, Sandhya; Patel, Hiren; Kapoor, Sona; Sriraman, Kalpana; Parte, Seema; Unni, Sreepoorna

doi:10.1093/humupd/dmw030

Cited by 105 publications

(88 citation statements)

References 283 publications

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“…BM-isolated VSELs have been shown to remain as precursors of TCSCs for several types of cells, including hematopoietic cells, mesenchymal cells, endothelial cells, lung alveolar epithelial cells, and cardiomyocytes [11–18, 83, 84]. At the same time, VSELs isolated from murine and human gonads have been proposed to be precursors of male and female gametes [6, 8–10]. …”

Section: Introductionmentioning

confidence: 99%

Prolonged Growth Hormone/Insulin/Insulin-like Growth Factor Nutrient Response Signaling Pathway as a Silent Killer of Stem Cells and a Culprit in Aging

Ratajczak

Bartke

Darżynkiewicz

2017

Stem Cell Rev and Rep

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The dream of slowing down the aging process has always inspired mankind. Since stem cells are responsible for tissue and organ rejuvenation, it is logical that we should search for encoded mechanisms affecting life span in these cells. However, in adult life the hierarchy within the stem cell compartment is still not very well defined, and evidence has accumulated that adult tissues contain rare stem cells that possess a broad trans-germ layer differentiation potential. These most-primitive stem cells—those endowed with pluripotent or multipotent differentiation ability and that give rise to other cells more restricted in differentiation, known as tissue-committed stem cells (TCSCs) - are of particular interest. In this review we present the concept supported by accumulating evidence that a population of so-called very small embryonic-like stem cells (VSELs) residing in adult tissues positively impacts the overall survival of mammals, including humans. These unique cells are prevented in vertebrates from premature depletion by decreased sensitivity to growth hormone (GH), insulin (INS), and insulin-like growth factor (IGF) signaling, due to epigenetic changes in paternally imprinted genes that regulate their resistance to these factors. In this context, we can envision nutrient response GH/INS/IGF signaling pathway as a lethal factor for these most primitive stem cells and an important culprit in aging.

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Section: Introductionmentioning

confidence: 99%

Prolonged Growth Hormone/Insulin/Insulin-like Growth Factor Nutrient Response Signaling Pathway as a Silent Killer of Stem Cells and a Culprit in Aging

Ratajczak

Bartke

Darżynkiewicz

2017

Stem Cell Rev and Rep

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“…OCT-4 antibody (ab19857, ABCAM, Cambridge, UK, raised from within residues 300 to the C-terminus of human Oct-4) used in the present study allowed identification of both the alternatively spliced isoforms of OCT-4. Nuclear OCT-4A is crucial to maintain pluripotent state and as the cell initiates differentiation, OCT-4 translocates to the cytoplasm (with no biological function) and eventually gets degraded and is lost in differentiated cells [2]. Similar nuclear and cytoplasmic OCT-4 localization (reflecting spliced variants OCT-4A and OCT-4B) in pluripotent and non-pluripotent human primordial germ cells (PGCs) has been reported by others also [7].…”

Section: Introductionmentioning

confidence: 66%

“…Interestingly the results show more significant effect of P and FSH on myometrial stem cells compared to E. However, further studies need to be undertaken to substantiate these findings. Effect of FSH treatment alone on uterine myometrial stem/progenitor cells was indeed striking and FSH receptor expression has been reported on stem cells in the testis, ovary and the hematopoietic system reviewed in [2]. …”

Section: Discussionmentioning

confidence: 99%

Very small embryonic-like stem cells (VSELs) in adult mouse uterine perimetrium and myometrium

Bhartiya

James

2017

J Ovarian Res

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We have earlier reported the presence of very small embryonic-like stem cells (VSELs) in adult mouse uterus along with slightly bigger progenitors termed endometrial stem cells (EnSCs) and their regulation by ovarian hormones thus demonstrating a crucial role played by them during proliferation, differentiation and remodeling of the endometrium. Present study is a brief communication wherein we have examined the effect of higher dose of estrogen (E, 2 μg/day), progesterone (P, 1 mg/day) and follicle stimulating hormone (FSH, 5 IU/day for 5 days) specifically on the myometrium and perimetrium surrounding the endometrium in bilaterally ovariectomized mice. Similar treatment with E & P was recently used in a study published in the journal Nature to study the effect of steroid hormones on hematopoietic stem cells and this treatment regimen helps achieve hormone levels observed during pregnancy. Quiescent spherical stem cells (lacking PCNA expression) with high nucleo-cytoplasmic ratio and nuclear OCT-4A were detected in the perimetrium of atrophied (bilaterally ovariectomized) uterus. PCNA expression was observed after treatment and cells with cytoplasmic OCT-4B were invariably observed in the myometrium. VSELs were clearly visualized after treatment and the effect of P and FSH was more prominent compared to E on the development of myometrium. It is speculated that stem cells with nuclear OCT-4A located in the perimetrium differentiate to give rise to endothelial and myometrial cells with cytoplasmic OCT-4B. Based on the results of present study and published reports showing the presence of pluripotent markers (OCT-4, NANOG and SOX2) in human myometrial side population and expression of particularly OCT-4A in human leiomyomas, we speculate that these nuclear OCT-4 positive stem cells located in the perimetrium are the possible tumor initiating cells leading to the development of leiomyomas rather than the mesenchymal cells which express cytoplasmic OCT-4B.

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“…Subsequently, some scholars stated that the bone marrow transplantation could repair damages to the ovarian functions caused by the chemotherapy drugs [53, 54]. In recent years, researchers have found that ovarian stem cells are always accompanied by a few, very small, embryonic stem cells in the adult mammalian ovary [55-57], and these human embryonic stem cells are found in the peripheral blood of young, middle-aged and elderly people [58]. Virant et al indicated that there is a potential connection between the VSELs and the germinal system as well as the hemapoiesis reconstruction process [59].…”

Section: Factors Related To Ovarian Stem Cell Nests Agingmentioning

confidence: 99%

Ovarian Stem Cell Nests in Reproduction and Ovarian Aging

Zheng

et al. 2017

Cell Physiol Biochem

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The fixed primordial follicles pool theory, which monopolized reproductive medicine for more than one hundred years, has been broken by the discovery, successful isolation and establishment of ovarian stem cells. It has brought more hope than ever of increasing the size of primordial follicle pool, improving ovarian function and delaying ovarian consenescence. Traditional view holds that stem cell aging contributes to the senility of body and organs. However, in the process of ovarian aging, the main factor leading to the decline of the reproductive function is the aging and degradation of ovarian stem cell nests, rather than the senescence of ovarian germ cells themselves. Recent studies have found that the immune system and circulatory system are involved in the formation of ovarian germline stem cell niches, as well as regulating the proliferation and differentiation of ovarian germline stem cells through cellular and hormonal signals. Therefore, we can improve ovarian function and delay ovarian aging by improving the immune system and circulatory system, which will provide an updated program for the treatment of premature ovarian failure (POF) and infertility.

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Endogenous, very small embryonic-like stem cells: critical review, therapeutic potential and a look ahead

Cited by 105 publications

References 283 publications

Prolonged Growth Hormone/Insulin/Insulin-like Growth Factor Nutrient Response Signaling Pathway as a Silent Killer of Stem Cells and a Culprit in Aging

Prolonged Growth Hormone/Insulin/Insulin-like Growth Factor Nutrient Response Signaling Pathway as a Silent Killer of Stem Cells and a Culprit in Aging

Very small embryonic-like stem cells (VSELs) in adult mouse uterine perimetrium and myometrium

Ovarian Stem Cell Nests in Reproduction and Ovarian Aging

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