Can we fix it? Evaluating the potential of placental stem cells for the treatment of pregnancy disorders

James, Joanna L.; Srinivasan, Suganya; Alexander, Megan; Chamley, Larry

doi:10.1016/j.placenta.2013.12.010

Cited by 33 publications

(33 citation statements)

References 57 publications

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“…However, experimental studies are hampered by ethical constraints to obtain tissues from early human gestation as well as difficulties in establishing self-renewing human trophoblast stem and progenitor cells from trophoblast isolates (34)(35)(36). As a consequence, alternative models, such as bone morphogenetic protein (BMP)-treated human ESCs (hESCs), have been developed, allowing in vitro formation of the trophoblast lineage (37,38).…”

Section: Discussionmentioning

confidence: 99%

Notch1 controls development of the extravillous trophoblast lineage in the human placenta

Haider

Meinhardt

Saleh

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

124

144

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Development of the human placenta and its different epithelial trophoblasts is crucial for a successful pregnancy. Besides fusing into a multinuclear syncytium, the exchange surface between mother and fetus, progenitors develop into extravillous trophoblasts invading the maternal uterus and its spiral arteries. Migration into these vessels promotes remodelling and, as a consequence, adaption of blood flow to the fetal–placental unit. Defects in remodelling and trophoblast differentiation are associated with severe gestational diseases, such as preeclampsia. However, mechanisms controlling human trophoblast development are largely unknown. Herein, we show that Notch1 is one such critical regulator, programming primary trophoblasts into progenitors of the invasive differentiation pathway. At the 12th wk of gestation, Notch1 is exclusively detected in precursors of the extravillous trophoblast lineage, forming cell columns anchored to the uterine stroma. At the 6th wk, Notch1 is additionally expressed in clusters of villous trophoblasts underlying the syncytium, suggesting that the receptor initiates the invasive differentiation program in distal regions of the developing placental epithelium. Manipulation of Notch1 in primary trophoblast models demonstrated that the receptor promotes proliferation and survival of extravillous trophoblast progenitors. Notch1 intracellular domain induced genes associated with stemness of cell columns, myc and VE-cadherin, in Notch1−fusogenic precursors, and bound to themycpromoter and enhancer region at RBPJκ cognate sequences. In contrast, Notch1 repressed syncytialization and expression of TEAD4 and p63, two regulators controlling self-renewal of villous cytotrophoblasts. Our results revealed Notch1 as a key factor promoting development of progenitors of the extravillous trophoblast lineage in the human placenta.

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Section: Discussionmentioning

confidence: 99%

Notch1 controls development of the extravillous trophoblast lineage in the human placenta

Haider

Meinhardt

Saleh

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

124

144

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“…The SM10 cell line is derived from the labyrinth layer of the mouse placenta, which is primarily involved in the transport of nutrients, such as glucose and amino acids, between the mother and the growing baby [3][4][5]. Proper development of the placenta is crucial for maintaining a healthy pregnancy, and abnormal development of the labyrinthine lineage could lead to reduced or altered transport of nutrients, which has been implicated in pregnancy-associated disorders such as preeclampsia, IUGR, and placental insufficiency [5][6][7][8].…”

Section: Fig 6 Ampk Knockdown Inhibits Glucose Transport (A)mentioning

confidence: 99%

“…Placental abnormalities have been implicated in a number of pregnancy-associated disorders such as preeclampsia, intrauterine growth restriction (IUGR), and placental insufficiency [6][7][8]. The possible effects of these placental disorders are not restricted to the health of the baby early in life, but can also persist into adulthood.…”

Section: Introductionmentioning

confidence: 99%

AMPK Knockdown in Placental Trophoblast Cells Results in Altered Morphology and Function

Carey

Albers

Doliboa

et al. 2014

Stem Cells and Development

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The placenta is a transient organ that develops upon the initiation of pregnancy and is essential for embryonic development and fetal survival. The rodent placenta consists of distinct lineages and includes cell types that are analogous to those that make up the human placenta. Trophoblast cells within the labyrinth layer, which lies closest to the fetus, fuse and come in contact with maternal blood, thus facilitating nutrient and waste exchange between the mother and the baby. Abnormalities of the placenta may occur as a result of cellular stress and have been associated with pregnancy-associated disorders: such as preeclampsia, intrauterine growth restriction, and placental insufficiency. Cellular stress has also been shown to alter proliferation and differentiation rates of trophoblast cells. This stress response is important for cell survival and ensures continued placental functionality. AMP-activated protein kinase is an important sensor of cellular metabolism and stress. To study the role of AMPK in the trophoblast cells, we used RNA interference to simultaneously knockdown levels of both the AMPK alpha isoforms, AMPKa1 and AMPKa2. SM10 trophoblast progenitor cells were transduced with AMPKa1/2 shRNA and stable clones were established to analyze the effects of AMPK knockdown on important cellular functions. Our results indicate that a reduction in AMPK levels causes alterations in cell morphology, growth rate, and nutrient transport, thus identifying an important role for AMPK in the regulation of placental trophoblast differentiation.

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“…Umbilical cord and decidua are important sources of MSCs in the maternal‐fetal interface [Schwab and Gargett, ; Cutler et al, ], in which several regions of umbilical cord have MSCs, including Wharton's jelly, artery, vein or cord lining [Mennan et al, ]. Our previous studies showed that both umbilical cord and decidua MSCs present slow proliferation, aberrant levels of cytokines, decreased angiogenesis‐regulation ability and abnormal immunoregulation in PE [Hwang et al, ; Li et al, ; James et al, ; Chen et al, ; Zhao et al, ]. Furthermore, we used normal MSCs to treat PE‐like mouse and got the ideal therapeutic effect [Liu et al, ].…”

mentioning

confidence: 99%

Long Non-Coding RNA MALAT1 Promotes Proliferation, Angiogenesis, and Immunosuppressive Properties of Mesenchymal Stem Cells by Inducing VEGF and IDO

Song

Liu

et al. 2017

J. Cell. Biochem.

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Mesenchymal stem cells (MSCs) play an important role in regulating angiogenesis and immune balance. The abnormal MSCs in proliferation and function were reported at maternal fetal interface in patients with pre-eclampsia (PE). Long non-coding RNA MALAT1 was known to regulate the function of trophoblast cells. However, it is not clear whether MALAT1 regulates MSCs to be related to PE. In the present study, we found that the expression of MALAT1 was significantly reduced in both umbilical cord tissues and MSCs in patients with severe PE. MALAT1 did not affect the phenotype and differentiation of MSCs. Of note, transfection with MALAT1 plasmid into MSCs drove the cell cycle into G2/M phase and inhibited cell apoptosis. The supernatants from MALAT1-overexpressed MSCs promoted the migration of MSCs, invasion of HTR-8/SVneo and tube formation of HUVEC, while si-MALAT1 had the opposite effects. Moreover, we found that MALAT1-induced VEGF mediated these effects of MALAT1 on MSCs. Furthermore, we found that MALAT1-overexpressed MSCs promoted M2 macrophage polarization and this effect was mediated by MALAT1-induced IDO expression, suggesting that MALAT1 may enhance the immunosuppressive properties of MSCs in vivo. In addition, we also investigated the factors that inhibit MALAT1 expression in PE and found that peroxide was a cause for MALAT1 downregulation. Taken together, our data demonstrate that MALAT1 is an important endogenous regulator in the proliferation, angiogenesis, and immunosuppressive properties of MSCs, suggesting it may be involved in the pathogenesis of PE. J. Cell. Biochem. 118: 2780-2791, 2017. © 2017 Wiley Periodicals, Inc.

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Can we fix it? Evaluating the potential of placental stem cells for the treatment of pregnancy disorders

Cited by 33 publications

References 57 publications

Notch1 controls development of the extravillous trophoblast lineage in the human placenta

Notch1 controls development of the extravillous trophoblast lineage in the human placenta

AMPK Knockdown in Placental Trophoblast Cells Results in Altered Morphology and Function

Long Non-Coding RNA MALAT1 Promotes Proliferation, Angiogenesis, and Immunosuppressive Properties of Mesenchymal Stem Cells by Inducing VEGF and IDO

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