Placental Stem Cells Research Articles

Biosponge-Encased Placental Stem Cells for Volumetric Muscle Loss Repair.

Objective: Volumetric muscle loss (VML) leads to permanent muscle mass and functional impairments. While mesenchymal stromal cells (MSCs) and their secreted factors can aid muscle regeneration, MSCs exhibit limited persistence in injured tissue post-transplantation. Human placental-derived stem cells (hPDSCs), sharing surface markers with MSCs, demonstrate superior regenerative potential due to their fetal origin. Previously, a biosponge (BS) scaffold was shown to augment muscle regeneration post-VML. This study aims to coapply BS therapy and hPDSCs to further enhance muscle recovery following VML. Approach: A VML defect was created by removing ∼20% of the tibialis anterior muscle mass in male Lewis rats. Injured muscles were either left untreated or treated with BS or BS-encapsulated hPDSCs cultured under normoxic or hypoxic conditions. On day 28 postinjury, peak isometric torque was measured, and the muscle was harvested for analysis. Results: BS encapsulated hPDSCs subjected to hypoxic preconditioning persisted in larger quantities and enhanced muscle mass at day 28 postinjury. BS encapsulated hPDSCs cultured under normoxic or hypoxic conditions increased small myofibers (<500 µm2) percentage, MyoD protein expression, and both pro- and anti-inflammatory macrophage marker expression. BS encapsulated hPDSCs also reduced fibrosis and BS remodeling rate. Innovation: This study is the first to examine the therapeutic effects of hPDSCs in a rat VML model. A BS carrier and hypoxic preconditioning were investigated to mitigate low cell survival postimplantation. Conclusion: hPDSCs augment the regenerative effect of BS. Combining hPDSCs and BS emerges as a promising strategy worthy of further investigation.

THE EFFECTIVENESS OF STEM CELL THERAPY IN MYOCARDIAL INFARCTION REVIEWED FROM UREUM, CREATININE AND KIDNEY HISTOPATHOLOGY LEVELS

This study aims to study the effectiveness of single placental stem cell therapy or cardiomyocyte combination in pigs experiencing myocardial infarction in terms of urea, creatinine and kidney organ histopathology values. A total of 9 pigs were divided int o three groups: without therapy (K1), single placental stem cell therapy (K2), and cardiomyocyte coculture combination therapy (K3). All pigs underwent circumflex artery ligation of the proximal coronary artery branch to stimulate cardiac ischemia and therapy was given after myocardial infarction and ST-elevation were formed. The pigs were then treated for eight weeks, euthanized and necropsied for kidney organ removal. The re sults showed a significant decrease in urea and creatinine values (P0.05) in K2 and K3 as compared to K1. Histopathology results showed a decrease in glomerular atrophy values (K2: 10.26±0.93 and K3: 12.44±1.21), tubular necrosis (K2: 13.67±3.76 and K3: 17.23±0.55), and tubular dilation (K2: 16.36±1.26 and K3: 18.03±1.76) and these values were significantly different than those observed in K1. It was concluded that the administration of placental stem cell therapy or combined with cardiomyocyte coculture could reduce urea, creatinine values, and improve kidney tissue histopathologically.

Prevention of post-operative adhesions: Model development and pilot outcomes of human placental stem cell-based interventions.

Abdominal adhesions are the most common surgical complication and without reliable prophylactics. This study presents a novel rat model for abdominal adhesions and reports pilot results of human placental stem cell (hPSC)-based therapies. Forty-four (n = 44) male Sprague-Dawley rats (250-350 g) were used in the experiment. Of these, thirty-eight (n = 38) were included in a preliminary data set to determine a minimum treatment effect. Adhesions were created in a reproducible model to the abdominal wall and between organs. Experimental groups included the control group (Model No Treatment, MNT), Plasmalyte A (Media Alone, MA, 10 mL), hPSC (5 × 106 cells/10 mL Plasmalyte A), hPSC-CM (hPSC secretome, conditioned media) in 10 mL Plasmalyte A, Seprafilm™ (Baxter, Deerfield, IL), and sham animals (laparotomy only). Treatments were inserted intraperitoneally (IP) and the study period was 14 days post-operation. Results are reported as the difference between means of an index statistic (AIS, Animal Index Score) and compared by ANOVA with pairwise comparison. The overall mean AIS was 23 (SD 6.16) for the MNT group with an average of 75% of ischemic buttons involved in abdominal adhesions. Treatment groups MA (mean overall AIS 17.33 SD 6.4), hPSC (mean overall AIS 13.86 SD 5.01), hPSC-CM (mean overall AIS 13.13 SD 6.15), and Seprafilm (mean overall AIS 13.43 SD 9.11) generated effect sizes of 5.67, 9.14, 9.87, and 9.57 decrease in mean overall AIS, respectively, versus the MNT. The presented rat model and scoring system represent the clinical adhesion disease process. hPSC-based interventions significantly reduce abdominal adhesions in this pilot dataset.

Optimization of a nanoparticle uptake protocol applied to amniotic-derived cells: unlocking the therapeutic potential.

Stem cell-based therapy implementation relies heavily on advancements in cell tracking. The present research has been designed to develop a gold nanorod (AuNR) labeling protocol applied to amniotic epithelial cells (AECs) leveraging the pro-regenerative properties of this placental stem cell source which is widely used for both human and veterinary biomedical regenerative applications, although not yet exploited with tracking technologies. Ovine AECs, in native or induced mesenchymal (mAECs) phenotypes via epithelial-mesenchymal transition (EMT), served as the model. Initially, various uptake methods validated on other sources of mesenchymal stromal cells (MSCs) were assessed on mAECs before optimization for AECs. Furthermore, the protocol was implemented by adopting the biological strategy of MitoCeption to improve endocytosis. The results indicate that the most efficient, affordable, and easy protocol leading to internalization of AuNRs in living mAECs recognized the combination of the one-step uptake condition (cell in suspension), centrifugation-mediated internalization method (G-force) and MitoCeption (mitochondrial isolated from mAECs). This protocol produced labeled vital mAECs within minutes, suitable for preclinical and clinical trials. The optimized protocol has the potential to yield feasible labeled amniotic-derived cells for biomedical purposes: up to 10 million starting from a single amniotic membrane. Similar and even higher efficiency was found when the protocol was applied to ovine and human AECs, thereby demonstrating the transferability of the method to cells of different phenotypes and species-specificity, hence validating its great potential for the development of improved biomedical applications in cell-based therapy and diagnostic imaging.

Bisphenol S moderately decreases the expression of syncytiotrophoblast marker genes and induces apoptosis in human trophoblast lineages

Bisphenol S (BPS) is currently used in the manufacturing of several household equipment such as water pipes and food containers. Hence, its entrance into the human body is almost inevitable. The presence of BPS in body fluids has been reported. However, its potential toxicity, especially on human placenta development and pregnancy progression, has not been explored. In this study, we assessed the impacts of BPS on the self-renewal and differentiation potentials of placental stem cells, also known as trophoblast stem cells (TSCs), by exposing them to three different BPS concentrations during their self-renewal and differentiation into syncytiotrophoblast (ST), extravillous trophoblast (EVT), and trophoblast organoids. Interestingly, BPS treatment did not affect the stemness, cell cycle and proliferation of the TSCs but it induced apoptosis in each trophoblast lineage. BPS altered the expression of several fusion-related genes. However, this alteration did not translate into significant morphological defects in the STs and organoids. Moreover, BPS did not impair the differentiation of TSCs into EVTs. These findings suggest that the presence of BPS at the feto-maternal interface may exaggerate trophoblast apoptosis and moderately inhibit the trophoblast fusion pathway to affect placenta development and pregnancy. Our study offers valuable insights into the potential toxicity of BPS on human placenta development, emphasizing the need for epidemiological assessment of the relationship between maternal serum levels of BPS and pregnancy complications.

Amniotic Membrane and Amniotic Epithelial Cell Culture.

Amniotic membrane (AM) is considered an important medical device for applications in regenerative medicine. The therapeutic properties of AM are due to its resistant extracellular matrix and to the large number of bioactive molecules released by its cells. To this regard, ovine amniotic epithelial cells (AECs) are a subset of placental stem cells with great regenerative and immunomodulatory properties. Indeed, either oAEC or AM have been object of intense study for regenerative medicine, thanks to several advantages in developing preclinical studies on a high value translational animal model, such as sheep. For this reason, a critical standardization of cultural practices is fundamental in order to maintain, on one hand, AM integrity and structure and, on the other hand, oAEC native properties, thus improving their in vivo therapeutic potential and clinical outcomes.In addition, freshly isolated AECs or AM can be exploited to produce enriched immunomodulatory secretomes that had been used with success into cell-free regenerative medicine procedures.To this aim, here is described an improved oAEC cultural protocol able to preserve their native epithelial phenotype also after the in vitro amplification and an innovative AM in vitro cultural protocol design to prolong the integrity and the biological properties of this tissue in order to collect stable conditioned media enriched with immunomodulatory factors.

Modeling the Progression of Placental Transport from Early- to Late-Stage Pregnancy by Tuning Trophoblast Differentiation and Vascularization.

The early-stage placental barrier is characterized by a lack of fetal circulation and by a thick trophoblastic barrier, whereas the later-stage placenta consists of vascularized chorionic villi encased in a thin, differentiated trophoblast layer, ideal for nutrient transport. In this work, predictive models of early- and late-stage placental transport are created using blastocyst-derived placental stem cells (PSCs) by modulating PSC differentiation and model vascularization. PSC differentiation results in a thinner, fused trophoblast layer, as well as an increase in human chorionic gonadotropin secretion, barrier permeability, and secretion of certain inflammatory cytokines, which are consistent with in vivo findings. Further, gene expression confirms this shift toward a differentiated trophoblast subtype. Vascularization results in a molecule type- and size-dependent change in dextran and insulin permeability. These results demonstrate that trophoblast differentiation and vascularization have critical effects on placental barrier permeability and that this model can be used as a predictive measure to assess fetal toxicity of xenobiotic substances at different stages of pregnancy.

Generation of trophoblast models from human pluripotent stem cells: insights into the signaling requirements of human placental stem cells.

Generation of trophoblast models from human pluripotent stem cells: insights into the signaling requirements of human placental stem cells.

Cell surface associated protein mucin 15 (MUC15) is elevated in preeclampsia

BackgroundMucins are a family of proteins that protect the epithelium. A particular type of mucin, MUC15 is highly expressed in the placenta. This study aimed to characterise MUC15 in preeclampsia and investigate its role in placental stem cell biology. MethodsMUC15 mRNA and protein were measured in placentas from patients with early onset (<34 weeks’ gestation) preeclampsia. Circulating serum MUC15 was measured via ELISA. MUC15 was localised in the placenta using in situ hybridisation. MUC15 mRNA expression was measured across differentiation of human trophoblast stem cells (hTSCs) to syncytiotrophoblast and extravillous trophoblasts. MUC15 was measured after syncytialised hTSCs were cultured in hypoxic (1% O2) and proinflammatory (TNF α, IL-6) conditions. MUC15 secretion was assessed when syncytialised hTSCs were treated with brefeldin A (impairs protein trafficking) and batimastat (inhibits matrix metalloproteinases). ResultsMUC15 protein was significantly increased in the placenta (P = 0.0003, n = 32 vs n = 20 controls) and serum (P = 0.016, n = 32 vs n = 22 controls) of patients with preeclampsia, whilst MUC15 mRNA remained unchanged (n = 61 vs n = 18 controls). MUC15 mRNA (P = 0.005) and protein secretion (P = 0.006) increased following differentiation to syncytiotrophoblast cells. In situ hybridisation confirmed MUC15 localised to the syncytiotrophoblast cell within the placenta. Neither hypoxic or inflammatory conditions changed MUC15 mRNA expression or secretion. Brefeldin A treated hTSCs did not alter MUC15 secretion, whilst batimastat reduced MUC15 secretion (P = 0.044). ConclusionsMUC15 is increased in early onset preeclampsia and is cleaved by matrix metalloproteinases. Increased MUC15 may reflect a protective mechanism associated with placental dysfunction. Further research will aid in confirming this.

Endometrial and placental stem cells in successful and pathological pregnancies.

The endometrium is a dynamic tissue that undergoes extensive remodeling during the menstrual cycle and further gets modified during pregnancy. Different kinds of stem cells are reported in the endometrium. These include epithelial stem cells, endometrial mesenchymal stem cells, side population stem cells, and very small embryonic-like stem cells. Stem cells are also reported in the placenta which includes trophoblast stem cells, side population trophoblast stem cells, and placental mesenchymal stem cells. The endometrial and placental stem cells play a pivotal role in endometrial remodeling and placental vasculogenesis during pregnancy. The dysregulation of stem cell function is reported in various pregnancy complications like preeclampsia, fetal growth restriction, and preterm birth. However, the mechanisms by which it does so are yet elusive. Herein, we review the current knowledge of the different type of stem cells involved in pregnancy initiation and also highlight how their improper functionality leads to pathological pregnancy.

PD19-03 THE DELIVERY OF THE RECOMBINANT PROTEIN COCKTAIL IDENTIFIED BY STEM CELL-DERIVED SECRETOME ANALYSIS ACCELERATES KIDNEY REPAIR AFTER RENAL ISCHEMIA-REPERFUSION INJURY

You have accessJournal of UrologyCME1 Apr 2023PD19-03 THE DELIVERY OF THE RECOMBINANT PROTEIN COCKTAIL IDENTIFIED BY STEM CELL-DERIVED SECRETOME ANALYSIS ACCELERATES KIDNEY REPAIR AFTER RENAL ISCHEMIA-REPERFUSION INJURY Ji Hyun Kim, Heejo Yang, Michael Kim, Kang Su Cho, Doo Sang Kim, Hyung Eun Yim, Zachary Atala, John Jackson, In Kap Ko, and James Yoo Ji Hyun KimJi Hyun Kim More articles by this author , Heejo YangHeejo Yang More articles by this author , Michael KimMichael Kim More articles by this author , Kang Su ChoKang Su Cho More articles by this author , Doo Sang KimDoo Sang Kim More articles by this author , Hyung Eun YimHyung Eun Yim More articles by this author , Zachary AtalaZachary Atala More articles by this author , John JacksonJohn Jackson More articles by this author , In Kap KoIn Kap Ko More articles by this author , and James YooJames Yoo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003285.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Renal disease is a worldwide health issue. Stem cell therapies have been proposed to restore damaged kidneys as an alternative to renal replacement therapies. In addition to stem cell therapies, recent studies have shown that stem cell-derived secretomes or conditioned media (CM) can enhance tissue regeneration. Our previous study demonstrated that the controlled delivery of human placental stem cells (hPSC)-derived CM using platelet-rich plasma (PRP) improved histological and functional recovery in an acute kidney injury (AKI) model in rats. The protein analysis of hPSC-CM showed the five highly expressed proteins that promote kidney repair. Based on our results, we propose that these proteins could be used as a recombinant protein cocktail to treat kidney diseases as an alternative to using CM. This study investigated the feasibility of delivering the recombinant protein cocktail for kidney repair after AKI. METHODS: The effects of the recombinant protein cocktail on human renal cell survival, proliferation, and apoptosis were compared with the CM in vitro. The feasibility of delivering the recombinant protein cocktail with a PRP system to achieve structural and functional recovery after AKI was investigated. RESULTS: The pro-proliferative and anti-apoptotic effects of the protein cocktail on renal cells were demonstrated in vitro and in vivo. The intrarenal delivery of these proteins with PRP ameliorates the renal tubular damage and improved renal function in the AKI-induced rats, yielding similar therapeutic effects compared to the CM delivery. CONCLUSIONS: The delivery of RPC can support renal cell survival and proliferation in vitro and in vivo, resulting in the attenuation of renal tubular damages and amelioration of renal function in the AKI model in rats. Our strategy may provide a therapeutic solution to many challenges associated with kidney repair resulting from the lack of suitable off-the-shelf regenerative medicine products. Source of Funding: This work was supported by the State of North Carolina © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e577 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ji Hyun Kim More articles by this author Heejo Yang More articles by this author Michael Kim More articles by this author Kang Su Cho More articles by this author Doo Sang Kim More articles by this author Hyung Eun Yim More articles by this author Zachary Atala More articles by this author John Jackson More articles by this author In Kap Ko More articles by this author James Yoo More articles by this author Expand All Advertisement PDF downloadLoading ...

Evaluation of amniotic fluid treatment effect on placental stem cells immunomodulatory activity

The advent of stem cell therapy in treating various complex diseases has become a major breakthrough in clinics. Mesenchymal stem cells are well known for their pluripotency and their immunomodulation feature, therefore research on mesenchymal stem cells is widely acknowledged. Obtaining viable stem cells with a less invasive extraction method as well as ethical issues is a major challenge in stem cell research. Recently, human placental stem cells are becoming more known as the best source of stem cells due to their ease of extraction, lesser ethical constraints, and presence of mesenchymal stem cells. Naturally derived bioactive compounds to modulate the proliferation, regeneration, cell fate and immunomodulation feature of stem cells are under investigation. In the current in-vitro study, the placenta-derived mesenchymal stem cells were treated with amniotic fluid and were observed for their effects. Our results suggest amniotic fluid treatment enhanced proliferation and induced mesenchymal to the epithelial transition of stem cells. Further, we observed changes in the secretion pattern of cytokines as well as growth factors, which are involved in T-cell suppression. Notable, the of TGFβ (17.4 ± 2.3 ng/ml) and IL-10 (21.7 ± 1.9 pg/ml) with the increase in the concentration of AF whereas the TNFα (8.6 ± 2.1 pg/ml) and IL-6 (12.3 ± 1.6 pg/ml) showed a decline in expression cytokine.Our results suggest amniotic fluid treatment can induce host cell immune suppression; however further validation studies have to be carried out.

COMPARATIVE STUDY BETWEEN DELAYED UMBILICAL CORD CLAMPING AND MILKING OF UMBILICAL CORD IN REGARD OF HEMATOCRIT LEVELAND NEURODEVELOPMENTAL OUTCOME AMONG PRETERM/LOW BIRTH WEIGHT BABIES IN A TERTIARY CARE HOSPITAL OF WEST BENGAL

Introduction: It is well established that Delayed cord clamping, in which cord is clamped only after a short delay (30 to 180 sec) after birth, improves iron status, reduce anemia and need for blood transfusion in later life, and also provides higher amount of placental stem cells to the infant without causing signicant harm to the mother and baby. Aims: To Compare Haematocrit level after 48 hours of age in preterm and low birth weight babies between the delayed umbilical cord clamping and umbilical cord milking and to compare neurodevelopmental outcome at third and six completed months of age in preterm and low birth weight babies between the delayed umbilical cord clamping and umbilical cord milking. Materials and Methods:The present study was a Hospital based Interventional study. This study was conducted from January 2021 – June 2022at Labour Room and operation theatre of College of Medicine &amp; Sagore Dutta Hospital, Kolkata-700058, a tertiary centre in West Bengal.80 patients were included in this study. Result:In our study, higher number of patients had Neck Holding(6 months) [29 (72.5%)]in Milking of Umbilical Cord compared to Delayed Umbilical Cord Clamping [27 (67.5%)] but this was not statistically signicant (p=0.6255) And higher number of patients had Roll Over(6 months) [29(72.5%)]in Milking of Umbilical Cord compared to Delayed Umbilical Cord Clamping [27 (67.5%)] though it was not statistically signicant (p=0.1432). Conclusion: It was found that, the mean Birth Weight (gm.) was not signicantly lower in Milking of Umbilical Cord compared to Delayed Umbilical Cord Clamping. And the mean Haemoglobin at 48 hours was signicantly lower in Milking of Umbilical Cord compared to Delayed Umbilical Cord Clamping.

Knowledge and Practice about Placental Stem Cell and its Utilisation among Various Health Professionals

Knowledge and Practice about Placental Stem Cell and its Utilisation among Various Health Professionals

Placental galectin-3 is reduced in early-onset preeclampsia.

Preeclampsia is a disease of pregnancy responsible for significant maternal and neonatal mortality. Galectin-3 is a β-Galactoside binding protein. This study aimed to characterise galectin-3 in women with preeclampsia and human trophoblast stem cells (hTSCs). Galectin-3 was measured in placental lysates and plasma collected from patients with early-onset preeclampsia (delivered <34 weeks’ gestation) and gestation matched controls. Placental galectin-3 protein was significantly reduced in 43 women with early-onset preeclampsia compared to 21 controls. mRNA expression of LGALS3 (galectin-3 encoding gene) was reduced in 29 women with early-onset preeclampsia, compared to 18 controls (p = 0.009). There was no significant difference in plasma galectin-3 protein in 46 women with early-onset preeclampsia compared to 20 controls. In a separate cohort of samples collected at 36 weeks’ gestation, circulating galectin-3 was not altered in 23 women who later developed preeclampsia, versus 182 who did not. In syncytialised hTSCs, hypoxia increased mRNA expression of LGALS3 (p = 0.01). Treatment with inflammatory cytokines (TNF-α and IL-6) had no effect on LGALS3 mRNA expression. However, TNF-α treatment caused an increase in mRNA expression of LGALS3BP (galectin-3 binding protein encoding gene) in hTSCs (p = 0.03). This study showed a reduction of galectin-3 in placenta from pregnancies complicated by early-onset preeclampsia. LGALS3 mRNA expression was dysregulated by hypoxia exposure in placental stem cells.

Using high throughput screens to predict miscarriages with placental stem cells and long-term stress effects with embryonic stem cells.

A problem in developmental toxicology is the massive loss of life from fertilization through gastrulation, and the surprising lack of knowledge of causes of miscarriage. Half to two-thirds of embryos are lost, and environmental and genetic causes are nearly equal. Simply put, it can be inferred that this is a difficult period for normal embryos, but that environmental stresses may cause homeostatic responses that move from adaptive to maladaptive with increasing exposures. At the lower 50% estimate, miscarriage causes greater loss-of-life than all cancers combined or of all cardio- and cerebral-vascular accidents combined. Surprisingly, we do not know if miscarriage rates are increasing or decreasing. Overshadowed by the magnitude of miscarriages, are insufficient data on teratogenic or epigenetic imbalances in surviving embryos and their stem cells. Superimposed on the difficult normal trajectory for peri-gastrulation embryos are added malnutrition, hormonal, and environmental stresses. An overarching hypothesis is that high throughput screens (HTS) using cultured viable reporter embryonic and placental stem cells (e.g., embryonic stem cells [ESC] and trophoblast stem cells [TSC] that report status using fluorescent reporters in living cells) from the pre-gastrulation embryo will most rapidly test a range of hormonal, environmental, nutritional, drug, and diet supplement stresses that decrease stem cell proliferation and imbalance stemness/differentiation. A second hypothesis is that TSC respond with greater sensitivity in magnitude to stress that would cause miscarriage, but ESC are stress-resistant to irreversible stemness loss and are best used to predict long-term health defects. DevTox testing needs more ESC and TSC HTS to model environmental stresses leading to miscarriage or teratogenesis and more research on epidemiology of stress and miscarriage. This endeavor also requires a shift in emphasis on pre- and early gastrulation events during the difficult period of maximum loss by miscarriage.

Features of immunohistochemical markers of stem CELLS CD-117, CD-44 in female placentas on the background of chronic stress

Background. Placenta is a subject of interest to a wide range of scientists because it is rich in stem cells and their precursors. A stem cell is a cell that has the ability to self-repair and can differentiate into offspring (daughter cells) of one or more germ layers. In recent years, scientists have obtained new data of stem cells regenerative potential. However, only isolated publications about placental stem cells are available. Therefore, our studies about placental stem cells are important for discovery of structural and molecular mechanisms, their changes under the influence of chronic stress.Objective: to study the features of immunohistochemical markers of pluripotent stem cells and their morphological features.Materials and methods. We examined 80 women placentas with chronic stress in comparison with control using general histological and immunohistochemical methods in the following groups: group 1 – women placentas with physiological course of pregnancy in term 38–40 weeks, group 2 – women placentas with miscarriage, group 3 – women placentas with chronic stress due to internal irradiation (4.5 Bq/kg and more), group 4 – women placentas which had COVID-19 during pregnancy.Results. There was a significant increase of stem cell markers expression in the three study groups with a significant predominance in groups 3 and 4. It was also determined the different direction of their active factors.Conclusions. The general changes of all structures of the placental barrier are detected as a result of chronic stress due to various factors: micro detachment of the decidual membrane (significant increase in cases in the studied groups); malperfusion in the structures of the maternal placental barrier; in the placenta stem cells of the three study groups in comparison with the control were found stress markers. Thus, chronic stress due to various factors causes the same type of changes in placental structures, but they have different degrees of expression – with internal irradiation doses ≥ 4.8 Bq/kg, these changes are most expressive.

Inhibition of Epithelial-Mesenchymal Transition Maintains Stemness in Human Amniotic Epithelial Cells

Human amniotic epithelial cells (hAECs), which are a type of placental stem cell, express stem cell marker genes and are capable of differentiating into all three germ layers under appropriate culture conditions. hAECs are known to undergo TGF-β-dependent epithelial-mesenchymal transition (EMT); however, the impact of EMT on the stemness or differentiation of hAECs has not yet been determined. Here, we first confirmed that hAECs undergo EMT immediately after starting primary culture. Comprehensive transcriptome analysis using RNA-seq revealed that inhibition of TGF-β-dependent EMT maintained the expression of stemness-related genes, including NANOG and POU5F1, in hAECs. Moreover, the maintenance of stemness did not affect the nontumorigenic characteristics of hAECs. We showed for the first time that TGF-β-dependent EMT negatively affected the stemness of hAECs, providing novel insight into cellular processes of placental stem cells.Graphical abstract

Aspirin-Mediated Reset of Preeclamptic Placental Stem Cell Transcriptome - Implication for Stabilized Placental Function.

Preeclampsia (PE) is a pregnancy-specific disease, occurring in ~ 2-10% of all pregnancies. PE is associated with increased maternal and perinatal morbidity and mortality, hypertension, proteinuria, disrupted artery remodeling, placental ischemia and reperfusion, and inflammation. The mechanism of PE pathogenesis remains unresolved explaining limited treatment. Aspirin is used to reduce the risk of developing PE. This study investigated aspirin's effect on PE-derived placenta mesenchymal stem cells (P-MSCs). P-MSCs from chorionic membrane (CM), chorionic villi, membranes from the maternal and amniotic regions, and umbilical cord were similar in morphology, phenotype and multipotency. Since CM-derived P-MSCs could undergo long-term passages, the experimental studies were conducted with this source of P-MSCs. Aspirin (1mM) induced significant functional and transcriptomic changes in PE-derived P-MSCs, similar to healthy P-MSCs. These include cell cycle quiescence, improved angiogenic pathways, and immune suppressor potential. The latter indicated that aspirin could induce an indirect program to mitigate PE-associated inflammation. As a mediator of activating the DNA repair program, aspirin increased p53, and upregulated genes within the basic excision repair pathway. The robust ability for P-MSCs to maintain its function with high dose aspirin contrasted bone marrow (M) MSCs, which differentiated with eventual senescence/aging with 100 fold less aspirin. This difference cautions how data from other MSC sources are extrapolated to evaluate PE pathogenesis. Dysfunction among P-MSCs in PE involves a network of multiple pathways that can be restored to an almost healthy functional P-MSC. The findings could lead to targeted treatment for PE.

Identification and characterization of stem cell secretome-based recombinant proteins for wound healing applications.

Stem cells have been introduced as a promising therapy for acute and chronic wounds, including burn injuries. The effects of stem cell-based wound therapies are believed to result from the secreted bioactive molecules produced by stem cells. Therefore, treatments using stem cell-derived conditioned medium (CM) (referred to as secretome) have been proposed as an alternative option for wound care. However, safety and regulatory concerns exist due to the uncharacterized biochemical content and variability across different batches of CM samples. This study presents an alternative treatment strategy to mitigate these concerns by using fully characterized recombinant proteins identified by the CM analysis to promote pro-regenerative healing. This study analyzed the secretome profile generated from human placental stem cell (hPSC) cultures and identified nine predominantly expressed proteins (ANG-1, FGF-7, Follistatin, HGF, IL-6, Insulin, TGFβ-1, uPAR, and VEGF) that are known to contribute to wound healing and angiogenesis. These proteins, referred to as s (CMFs), were used in combination to test the effects on human dermal fibroblasts (HDFs). Our results showed that CMF treatment increased the HDF growth and accelerated cell migration and wound closure, similar to stem cell and CM treatments. In addition, the CMF treatment promoted angiogenesis by enhancing new vessel formation. These findings suggest that the defined CMF identified by the CM proteomic analysis could be an effective therapeutic solution for wound healing applications. Our strategy eliminates the regulatory concerns present with stem cell-derived secretomes and could be developed as an off-the-shelf product for immediate wound care and accelerating healing.