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The need to revisit the definition of mesenchymal and adult stem cells based on their functional attributes

A debate is ongoing about the ‘stem cell’ status of mesenchymal stem cells (MSCs). This can easily be resolved based on the definition of a stem cell. ‘True’ stem cells are expected to undergo asymmetric cell divisions (ACD) whereby they divide to self-renew and give rise to a slightly bigger, differentiated cell. However, MSCs like any other adult tissue-specific stem cells...

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

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...

Ovarian stem cells are always accompanied by very small embryonic-like stem cells in adult mammalian ovary

Background Existing dogma that a female is born with fixed number of eggs was challenged by the detection of stem cells in adult mammalian ovary. Data has accumulated in support of ovarian stem cells (OSCs) proliferation, maintenance in culture, formation of germ cell nests and differentiation into oocytes and primordial follicle assembly using different strategies. Results Flow...

Very small embryonic-like stem cells are involved in pancreatic regeneration and their dysfunction with age may lead to diabetes and cancer

Bhartiya 0 Hiren Patel 0 0 Stem Cell Biology Department, National Institute for Research in Reproductive Health , JM Street, Parel, Mumbai 400012 , India Mouse pancreas has a remarkable ability to

Delineating the effects of 5-fluorouracil and follicle-stimulating hormone on mouse bone marrow stem/progenitor cells

Background Pluripotent, Lin–/CD45–/Sca-1+ very small embryonic-like stem cells (VSELs) in mouse bone marrow (BM) are resistant to total body radiation because of their quiescent nature, whereas Lin–/CD45+/Sca-1+ hematopoietic stem cells (HSCs) get eliminated. In the present study, we provide further evidence for the existence of VSELs in mouse BM and have also examined the...

VSELs may obviate cryobanking of gonadal tissue in cancer patients for fertility preservation

Background Infertility is an undesirable side effect and gonadal tissue banking is advocated in young cancer patients who are unable to preserve embryos or gametes prior to oncotherapy to achieve biological parenthood later on. Banking gonadal tissue is challenging and protocols to mature gametes in vitro are not yet clinically established. Transplanting ovarian cortical tissue...

Chemoablated mouse seminiferous tubular cells enriched for very small embryonic-like stem cells undergo spontaneous spermatogenesis in vitro

Sandhya Anand 0 Hiren Patel 0 Deepa Bhartiya 0 Equal contributors Stem Cell Biology Department, National Institute for Research in Reproductive Health , Mumbai 400 012 , India Background: Extensive

The continued presence of stem cells and oogonia in the adult mammalian ovary

Deepa Bhartiya 0 0 Stem Cell Biology Department, National Institute for Research in Reproductive Health , Mumbai, India Bhartiya D, Kasiviswanathan S, Unni SK, Pethe P, Dhabalia JV, Patwardhan S

Very small embryonic-like stem cells are the elusive mouse endometrial stem cells- a pilot study

Background Endometrium undergoes dramatic growth, breakdown and regeneration throughout reproductive period in mammals. Stem cells have been implicated in the process however their origin, nature, anatomical localization and characterization still remain obscure. Classical concept of presence of stem cells in the basal layer of endometrium was recently challenged when side...

Polycomb group protein expression during differentiation of human embryonic stem cells into pancreatic lineage in vitro

Prasad Pethe 0 Punam Nagvenkar 0 Deepa Bhartiya 0 0 Stem Cell Biology Department, National Institute for Research in Reproductive Health , J.M. Street, Parel-12, Mumbai , India Background: Polycomb

Very small embryonic-like stem cells are involved in regeneration of mouse pancreas post-pancreatectomy

Introduction Despite numerous research efforts, mechanisms underlying regeneration of pancreas remains controversial. Views are divided whether stem cells are involved during pancreatic regeneration or it involves duplication of pre-existing islets or ductal cells or whether pancreatic islet numbers are fixed by birth or they renew throughout life. Pluripotent embryonic stem (ES...

Making gametes from pluripotent stem cells – a promising role for very small embryonic-like stem cells

The urge to have one’s own biological child supersedes any desire in life. Several options have been used to obtain gametes including pluripotent stem cells (embryonic ES and induced pluripotent iPS stem cells); gonadal stem cells (spermatogonial SSCs, ovarian OSCs stem cells), bone marrow, mesenchymal cells and fetal skin. However, the field poses a huge challenge including...

Ovarian stem cells: absence of evidence is not evidence of absence

Background Lei and Spradling in a recent study published in PNAS failed to detect ‘germline cysts’ by elegant studies using lineage tracing approach and thus concluded that adult mouse ovaries lack stem cells. They proposed that primordial follicle pool generated during fetal life is sufficient to sustain oogenesis and that there is no renewal of oocytes during adult life...

Dynamics associated with spontaneous differentiation of ovarian stem cells in vitro

Background Recent studies suggest that ovarian germ line stem cells replenish oocyte-pool in adult stage, and challenge the central doctrine of ‘fixed germ cell pool’ in mammalian reproductive biology. Two distinct populations of spherical stem cells with high nucleo-cytoplasmic ratio have been recently identified in the adult mammalian ovary surface epithelium (OSE) including...

Gonadotropin treatment augments postnatal oogenesis and primordial follicle assembly in adult mouse ovaries?

Background Follicle stimulating hormone (FSH) exerts action on both germline and somatic compartment in both ovary and testis although FSH receptors (FSHR) are localized only on the somatic cells namely granulosa cells of growing follicles and Sertoli cells in the seminiferous tubules. High levels of FSH in females are associated with poor ovarian reserve, ovarian hyper...

Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3

Background We have earlier reported that follicle stimulating hormone (FSH) modulates ovarian stem cells which include pluripotent, very small embryonic-like stem cells (VSELs) and their immediate descendants ‘progenitors’ termed ovarian germ stem cells (OGSCs), lodged in adult mammalian ovarian surface epithelium (OSE). FSH may exert pleiotropic actions through its alternatively...

Stimulation of ovarian stem cells by follicle stimulating hormone and basic fibroblast growth factor during cortical tissue culture

Background Cryopreserved ovarian cortical tissue acts as a source of primordial follicles (PF) which can either be auto-transplanted or cultured in vitro to obtain mature oocytes. This offers a good opportunity to attain biological parenthood to individuals with gonadal insufficiency including cancer survivors. However, role of various intra- and extra-ovarian factors during PF...

Expression of insulin-like growth factor-I and placental growth hormone mRNA in placentae: a comparison between normal and intrauterine growth retardation pregnancies*

Intrauterine growth restriction (IUGR) is generally defined as the pathological restriction of fetal growth resulting in a fetus with birth weight below the 10th percentile for gestational age. Almost 75% of IUGR cases develop during third trimester. Studies on animals (rodents and sheep) as well as humans suggest that insulin-like growth factor-I (IGF-I), under the influence of...

Stromal cell interaction and relevance to predecidual events and menstruation

Endometrial stromal cells play a vital role during decidual-ization and implantation. The aim of this study was to analyse the cyclic ultrastructural variations of stromal fibroblasts, granulocytes and blood-derived cells which invade the stroma during various stages of the menstrual cycle. Diverse opinions exist in the literature regarding the origin, fate and function of the...