• C3H mouse model
• adult cell therapy
• cell therapy
• expanded fetal human placental stromal cells (f-hPSCs)
• inflammatory bowel disease (IBD)

• Animals
• Dextran Sulfate/adverse effects
• Humans
• Mice
• Disease Models, Animal
• Female
• Colitis/therapy
• Colitis/chemically induced
• Colitis/pathology
• Pregnancy
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Mesenchymal Stem Cell Transplantation/methods
• Placenta/cytology
• Inflammatory Bowel Diseases/therapy

• (ISF# 1639/14) Israel Science Foundation

• diabetic kidney disease
• mesenchymal stem cell
• mesenchymal stem cell therapy

• Humans
• Diabetic Nephropathies/therapy
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells/cytology
• Animals
• Exosomes/transplantation
• Exosomes/metabolism

• 82370728, 81974096, 82170773, 81974097, 82100729, 82200808, 82200841, 82300843, and 82300786 National Natural Science Foundation of China
• 2021YFC2500200 National Key Research and Development Program of China
• 2023BCB034 Key Research and Development Program of Hubei Province

• Mesenchymal stem cells (MSCs)
• Multilineage differentiation
• Placenta-derived MSCs (PMSCs)
• Proliferation
• T cell proliferation inhibition

• Endometrium
• Mesenchymal stromal cells
• Myometrium
• Resveratrol
• Stem cells
• Uterus
• VSELs

• Female
• Animals
• Mice
• Vimentin
• Hyperplasia
• Pluripotent Stem Cells
• Embryonic Stem Cells
• Mesenchymal Stem Cells
• Neoplasms

• Indian Council of Medical Research Indian Council of Medical Research

• HMECs
• MDA231
• adhesion
• chorionic villus MSCs
• conditioned media
• epithelial to mesenchymal transition (EMT)
• flow cytometry
• invasion
• migration
• proliferation

• RC20/346 King Abdullah International Medical Research Center

• enzymatic method
• explant culture
• mesenchymal stromal cells
• perinatal tissues
• surface markers

• cell differentiation
• estrogen
• human amniotic mesenchymal stem cells
• intrauterine adhesions
• regeneration
• stem cell transplantation

• 3D printing
• biomaterials
• biomedical engineering
• infertility
• microfluidic technology
• reproductive medicine

Placenta-derived stem cells (PDSCs), due to unique traits such as mesenchymal and embryonic characteristics and the absence of ethical constraints, are in a clinically and therapeutically advantageous position. To aid in stemness maintenance, counter pathophysiological stresses, and withstand post-differentiation challenges, stem cells require elevated protein synthesis and consequently augmented proteostasis. Stem cells exhibit source-specific proteostasis traits, making it imperative to study them individually from different sources. These studies have implications for understanding stem cell biology and exploitation in the augmentation of therapeutic applications. Here, we aim to identify the primary determinants of proteotoxic stress response in PDSCs. We generated heat-induced dose-responsive proteotoxic stress models of three stem cell types: placental origin cells, the placenta-derived mesenchymal stem cells (pMSCs), maternal origin cells, the decidua parietalis mesenchymal stem cells (DPMSCs), and the maternal–fetal interface cells, decidua basalis mesenchymal stem cells (DBMSCs), and measured stress induction through biochemical and cell proliferation assays. RT-PCR array analysis of 84 genes involved in protein folding and protein quality control led to the identification of Hsp70 members HSPA1A and HSPA1B as the prominent ones among 17 significantly expressed genes and with further analysis at the protein level through Western blotting. A kinetic analysis of HSPA1A and HSPA1B gene and protein expression allowed a time series evaluation of stress response. As identified by protein expression, an active stress response is in play even at 24 h. More prominent differences in expression between the two homologs are detected at the translational level, alluding to a potential higher requirement for HSPA1B during proteotoxic stress response in PDSCs.

• HSPA1A
• HSPA1B
• chaperones
• heat shock
• placenta
• placenta-derived stem cells
• proteostasis
• stem cells
• stress response

The well-developed placentation is fundamental for the reproductive pregnancy while the defective placental development is the pathogenetic basis of preeclampsia (PE), a dangerous complication of pregnancy comprising the leading causes of maternal and perinatal morbidity and mortality. Placenta-derived mesenchymal stem cells (PMSCs) are a group of multipotent stem cells that own a potent capacity of differentiating into constitutive cells of vessel walls. Additionally, with the paracrine secretion of various factors, PMSCs inextricably link and interact with other component cells in the placenta, collectively improving the placental vasculature, uterine spiral artery remolding, and uteroplacental interface immunoregulation. Recent studies have further indicated that preeclamptic PMSCs, closely implicated in the abnormal crosstalk between other ambient cells, disturb the homeostasis and development in the placenta. Nevertheless, PMSCs transplantation or PMSCs exosome therapies tend to improve the placental vascular network and trophoblastic functions in the PE model, suggesting PMSCs may be a novel and putative therapeutic strategy for PE. Herein, we provide an overview of the multifaceted contributions of PMSCs in early placental development. Thereinto, the intensive interactions between PMSCs and other component cells in the placenta were particularly highlighted and further extended to the implications in the pathogenesis and therapeutic strategies of PE.

• differentiation
• mesenchymal stem cell
• paracrine
• placenta
• preeclampsia

• MDA231
• adhesion
• angiogenesis
• conditioned medium
• decidua parietalis MSCs
• invasion
• migration
• placenta
• proliferation

• PCR array
• chondrogenesis
• glycosaminoglycans
• microarray
• term placenta

• differentiation
• mesenchymal stem cells
• multipotent markers
• proliferation
• telomere length

• Adolescent
• Adult
• Cell Differentiation/physiology
• Cell Proliferation/physiology
• Female
• Humans
• Maternal Age
• Mesenchymal Stem Cells/physiology
• Placenta/cytology
• Pregnancy
• Telomere Shortening/physiology
• Young Adult

Mesenchymal stem/stromal cells (MSCs) are currently one of the most extensively researched fields due to their promising opportunity for use in regenerative medicine. There are many sources of MSCs, of which cells of perinatal origin appear to be an invaluable pool. Compared to embryonic stem cells, they are devoid of ethical conflicts because they are derived from tissues surrounding the fetus and can be safely recovered from medical waste after delivery. Additionally, perinatal MSCs exhibit better self-renewal and differentiation properties than those derived from adult tissues. It is important to consider the anatomy of perinatal tissues and the general description of MSCs, including their isolation, differentiation, and characterization of different types of perinatal MSCs from both animals and humans (placenta, umbilical cord, amniotic fluid). Ultimately, signaling pathways are essential to consider regarding the clinical applications of MSCs. It is important to consider the origin of these cells, referring to the anatomical structure of the organs of origin, when describing the general and specific characteristics of the different types of MSCs as well as the pathways involved in differentiation.

• MSCs differentiation
• perinatal mesenchymal stem/stromal cells
• signaling pathways

• Amniotic Fluid/cytology
• Cell Differentiation/genetics
• Cell Lineage/genetics
• Cell Self Renewal/genetics
• Embryonic Stem Cells/cytology
• Embryonic Stem Cells/transplantation
• Female
• Humans
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells/cytology
• Placenta/cytology
• Placenta/transplantation
• Pregnancy
• Regenerative Medicine
• Umbilical Cord/cytology
• Umbilical Cord/transplantation

• Autophagy
• Chorionic villous-derived mesenchymal stem cells
• JAK2/STAT3 signalling pathway
• Trophoblasts

• CD36
• atherosclerosis
• flow cytometry
• ox-LDL
• placental Mesenchymal Stem/Stromal cells
• platelet activation
• platelet aggregation
• platelet spreading

FURIN is a pro-protein convertase previously shown to be important for placental syncytialisation (Zhou et al. [1]), a process of cell fusion whereby placental cytotrophoblast cells fuse to form a multinucleated syncytium. This finding has been broadly accepted however, we have evidence suggesting the contrary. Spontaneously syncytialising term primary human trophoblast cells and BeWo choriocarcinoma cells were treated with either FURIN siRNA or negative control siRNA or the protease inhibitor, DEC-RVKR-CMK, or vehicle. Cells were then left to either spontaneously syncytialise (primary trophoblasts) or were induced to syncytialise with forskolin (BeWo). Effects on syncytialisation were measured by determining human chorionic gonadotrophin secretion and E-cadherin protein levels. We showed that FURIN is not important for syncytialisation in either cell type. However, in primary trophoblasts another protease also inhibited by DEC-RVKR-CMK, may be involved. Our results directly contrast with those published by Zhou et al. Zhou et al. however, used first trimester villous explants to study syncytialisation, and we used term primary trophoblasts. Therefore, we suggest that FURIN may be involved in syncytialisation of first trimester trophoblasts, but not term trophoblasts. What is more concerning is that our results using BeWo cells do not agree with their results, even though for the most part, we used the same experimental design. It is unclear why these experiments yielded different results, however we wanted to draw attention to simple differences in measuring syncytialisation or flaws in method reporting (including omission of cell line source and passage numbers, siRNA concentration and protein molecular weights) and choice of immunoblot loading controls, that could impact on experimental outcomes. Our study shows that careful reporting of methods by authors and thorough scrutiny by referees are vital. Furthermore, a universal benchmark for measuring syncytialisation is required so that various studies of syncytialisation can be validated.

Mesenchymal stem/stromal cells isolated from chorionic villi of human term placentae (CV-MSCs) possess unique biological characters. They exhibit self-renewal, directional migration, differentiation, and immunomodulatory effects on other cell lineages, by virtue of which they can be utilized as therapeutic carriers, for drug targeting, and therapy. Tumors display characteristic features of a damaged tissue microenvironment, which is saturated with conditions such as hypoxia, sustained inflammation, and increased oxidative stress. CV-MSCs function normally in a high oxidative stress environment induced by hydrogen peroxide (H₂O₂) and glucose and also protect endothelial cells from their damaging effects. For their therapeutic applications in a disease like cancer, it is necessary to ascertain the effects of tumor microenvironment on their functional outcome. In this study, we investigated the functional activities, of CV-MSCs in response to conditioned media (CM) obtained from the culture of breast cancer cell line MDA-231 (CM-MDA231). CV-MSCs were exposed to CM-MDA231 for different spatio-temporal conditions, and their biological functions as well as modulation in gene expression were evaluated. Effect of CM-MDA231 on factors responsible for changes in functional outcome were also investigated at the protein levels. CV-MSCs exhibited significant reduction in proliferation but increased adhesion and migration after CM-MDA231 treatment. Interestingly, there was no change in their invasion potential. CM-MDA231 treatment modulated expression of various genes involved in important cellular events including, integration, survival, message delivery and favorable outcome after transplantation. Analysis of pathways related to cell cycle regulation revealed significant changes in the expression of p53, and increased phosphorylation of Retinoblastoma (Rb) and Checkpoint Kinase 2 in CV-MSCs treated with CM-MDA231. To summarize, these data reveal that CV-MSCs retain the ability to survive, adhere, and migrate after sustained treatment with CM-MDA231, a medium that mimics the cancer microenvironment. These properties of CV-MSCs to withstand the inflammatory tumor like microenvironment prove that they may make useful candidate in a stem cell based therapy against cancer. However, further pre-clinical studies are needed to validate their therapeutic usage.

• MDA231
• adhesion
• chorionic villous MSCs
• conditioned medium
• invasion
• migration
• placenta
• proliferation

• Angiogenesis
• Fetal growth restriction
• Mesenchymal stem/stromal cells
• Placenta
• Placental macrophages
• Pregnancy

• adipose tissue stromal cells (atMSCs)
• bone marrow MSCs (bmMSC)
• cell-based immune modulation
• mesenchymal stromal/stem cells (MSC)
• placenta-derived mesenchymal stromal cells (hPSCs/pMSCs)
• pro-regenerative effects
• regenerative cell therapy
• xenogeneic cell delivery

• Adipose Tissue/metabolism
• Allografts/metabolism
• Animals
• Bone Marrow/metabolism
• Bone Marrow Cells/metabolism
• Cell Differentiation/physiology
• Cell Proliferation/physiology
• Cell- and Tissue-Based Therapy/methods
• Female
• Humans
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells/metabolism
• Placenta/metabolism
• Placenta/physiology
• Pregnancy
• Stromal Cells/metabolism

• 1639/14 Israel Science Foundation

Basic and preclinical research founded the progress of personalized medicine by providing a prodigious amount of integrated profiling data and by enabling the development of biomedical applications to be implemented in patient-centered care and cures. If the rapid development of genomics research boosted the birth of personalized medicine, further development in omics technologies has more recently improved our understanding of the functional genome and its relevance in profiling patients’ phenotypes and disorders. Concurrently, the rapid biotechnological advancement in diverse research areas enabled uncovering disease mechanisms and prompted the design of innovative biological treatments tailored to individual patient genotypes and phenotypes. Research in stem cells enabled clarifying their role in tissue degeneration and disease pathogenesis while providing novel tools toward the development of personalized regenerative medicine strategies. Meanwhile, the evolving field of integrated omics technologies ensured translating structural genomics information into actionable knowledge to trace detailed patients’ molecular signatures. Finally, neuroscience research provided invaluable models to identify preclinical stages of brain diseases. This review aims at discussing relevant milestones in the scientific progress of basic and preclinical research areas that have considerably contributed to the personalized medicine revolution by bridging the bench-to-bed gap, focusing on stem cells, omics technologies, and neuroscience fields as paradigms.

• genomics
• induced pluripotent stem cells
• mesenchymal stem cells
• neuroscience
• personalized medicine
• proteogenomics
• proteomics
• stem cells

Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be a useful source of cells for the treatment of many diseases, including neurologic diseases. The curative effect of MSCs relies mostly on cell’s capacity of migration, proliferation and differentiation. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles on regulating various cell behaviors. Here, we report that miRNA-124 (miR124) and miRNA-21-5p (miR21-5p) display different regulatory roles on migration, proliferation and neuron differentiation of MSCs. MiR124 was shown greatly promoting MSCs migration and neuronal differentiation. MiR21-5p could significantly enhance the proliferation and neuronal differentiation ability of MSCs. MiR124 and miR21-5p synergistically promote differentiation of MSCs into neurons. Collectively, miR124 and miR21-5p can functionally regulate cell migration, proliferation and neuronal differentiation of MSCs. Therefore, miR124 and miR21-5p may be promising tools to improve transplantation efficiency for neural injury.

• Differentiation
• MSCs
• MiRNA124
• MiRNA21
• Migration
• Proliferation

Neural crest stem cells (NCSCs) are a transient population of cells that arise during early vertebrate development and harbor stem cell properties, such as self‐renewal and multipotency. These cells form at the interface of non‐neuronal ectoderm and neural tube and undergo extensive migration whereupon they contribute to a diverse array of cell and tissue derivatives, ranging from craniofacial tissues to cells of the peripheral nervous system. Neural crest‐like stem cells (NCLSCs) can be derived from pluripotent stem cells, placental tissues, adult tissues, and somatic cell reprogramming. NCLSCs have a differentiation capability similar to NCSCs, and possess great potential for regenerative medicine applications. In this review, we present recent developments on the various approaches to derive NCLSCs and the therapeutic application of these cells for tissue regeneration.

• adult stem cells
• disease modeling
• neural crest stem cells
• placental stem cells
• regenerative medicine

• PLacental eXpanded
• coronavirus-induced disease 2019
• mesenchymal stromal cells
• perinatal
• severe acute respiratory distress syndrome coronavirus-2

• assisted reproductive medicine
• cell therapy
• endometrium
• infertility
• stem cells

• ophthalmology
• optic nerve
• placenta-derived stem cells
• stem cells
• trauma
• visual loss

• Cow
• Estrus rate
• Ovarian follicular cyst
• Placenta
• Recovery rate
• Stem cell

• cancer stem cells
• extracellular vesicles
• glioblastoma
• mesenchymal stem cells
• secretoma

• Brain Neoplasms/metabolism
• Brain Neoplasms/pathology
• Cell Differentiation
• Glioblastoma/metabolism
• Glioblastoma/pathology
• Humans
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells/metabolism

Intrauterine adhesion is a major cause of menstrual irregularities, infertility, and recurrent pregnancy losses and the progress towards its amelioration and therapy is slow and unsatisfactory. We aim to summarize and evaluate the current treatment progress and research methods for intrauterine adhesion. We conducted literature review in January 2020 by searching articles at PubMed on prevention and treatment, pathogenesis, the repair of other tissues/organs, cell plasticity, and the stem cell–related therapies for intrauterine adhesion. A total of 110 articles were selected for review. Uterine cell heterogeneity, expression profile, and cell-cell interaction were investigated based on scRNA-seq of uterus provided by Human Cell Landscape (HCL) project. Previous knowledge on intrauterine adhesion (IUA) pathogenesis was mostly derived from correlation studies by differentially expressed genes between endometrial tissue of intrauterine adhesion patients/animal models and normal endometrial tissue. Although the TGF-β1/SMAD pathway was suggested as the key driver for IUA pathogenesis, uterine cell heterogeneity and distinct expression profile among different cell types highlighted the importance of single-cell investigations. Cell-cell interaction in the uterus revealed the central hub of endothelial cells interacting with other cells, with endothelial cells in endothelial to mesenchymal transition and fibroblasts as the strongest interaction partners. The potential of stem cell–related therapies appeared promising, yet suffers from largely animal studies and nonstandard study design. The need to dissect the roles of endometrial cells, endothelial cells, and fibroblasts and their interaction is evident in order to elucidate the molecular and cellular mechanisms in both intrauterine adhesion pathogenesis and treatment.

• Cell heterogeneity
• Cell-cell interaction
• Intrauterine adhesion (IUA)
• Molecular mechanism
• TGF-β1/SMAD pathway

• Culture conditions
• EGM-2
• Maternal contamination
• Placenta
• Placental mesenchymal stem/stromal cells

The main aim of this review was to provide an updated comprehensive report regarding isolation methods of MSCs from human extra embryonic tissues, including cord blood, amniotic fluid, and different parts of the placenta and umbilical cord, with respect to the efficacy of these methods.

Extra embryonic tissues are the most available source for harvesting of mesenchymal stem cells (MSCs). They make a large number of cells accessible using non-invasive methods of isolation and the least immune-rejection reactions. A successful culture of primary cells requires obtaining a maximum yield of functional and viable cells from the tissues. In addition, there are many reports associated with their differentiation into various kinds of cells, and there are some clinical trials regarding their utilization for patients.

Currently, cord blood-MSCs have been tested for cartilage and lung diseases. Umbilical cord-MSCs were tested for liver and neural disorders. However, these MSCs can be isolated, expanded, and cryopreserved in a cell bank for patients in need.

• amniotic fluid
• cord blood-MSCs
• embryonic tissues
• immune-rejection
• placenta
• umbilical cord-MSCs

Selected placental mesenchymal stromal cells isolated from the fetal mesenchymal placental tissues (f-hPSCs) were tested as cell therapy of lethal acute radiation syndrome (ARS) with bone marrow regeneration and induced extramedullary hematopoiesis.

f-hPSCs were isolated from the chorionic plate of human placentae and further expanded in regular culture conditions. 2 × 10⁶ f-hPSCs were injected on days 1 and 4 to 8-Gy total body irradiated (TBI) C3H mice, both intramuscularly and subcutaneously. Pre-splenectomized TBI mice were used to test the involvement of extramedullary spleen hematopoiesis in the f-hPSC-induced hematopoiesis recovery in the TBI mice. Weight and survival of the mice were followed up within the morbid period of up to 23 days following irradiation. The role of hematopoietic progenitors in the recovery of treated mice was evaluated by flow cytometry, blood cell counts, and assay of possibly relevant growth factors.

The survival rate of all groups of TBI f-hPSC-treated mice at the end of the follow-up was dramatically elevated from < 10% in untreated to ~ 80%, with a parallel regain of body weight, bone marrow (BM) recovery, and elevated circulating progenitors of blood cell lineages. Blood erythropoietin levels were elevated in all f-hPSC-treated mice. Extramedullary splenic hematopoiesis was recorded in the f-hPSC-treated mice, though splenectomized mice still had similar survival rate. Our findings suggest that the indirect f-hPSC life-saving therapy of ARS may also be applied for treating other conditions with a failure of the hematopoietic system and severe pancytopenia.

• Acute radiation syndrome (ARS)
• Bone marrow
• C3H mice
• Extra-medullary hematopoiesis (EMH)
• Fetal human placental stromal cells (f-hPSCs)
• Hematopoiesis
• Hematopoietic stem cells (HSC)
• Spleen

Mesenchymal stem/stromal cells (MSCs) from the decidua basalis (DBMSCs) of the human placenta have important functions that make them potential candidates for cellular therapy. Previously, we showed that DBMSC functions do not change significantly in a high oxidative stress environment, which was induced by hydrogen peroxide (H₂O₂) and immune cells. Here, we studied the consequences of glucose, another oxidative stress inducer, on the phenotypic and functional changes in DBMSCs.

DBMSCs were exposed to a high level of glucose, and its effect on DBMSC phenotypic and functional properties was determined. DBMSC expression of oxidative stress and immune molecules after exposure to glucose were also identified.

Conditioning of DBMSCs with glucose improved their adhesion and invasion. Glucose also increased DBMSC expression of genes with survival, proliferation, migration, invasion, anti-inflammatory, anti-chemoattractant and antimicrobial properties. In addition, DBMSC expression of B7H4, an inhibitor of T cell proliferation was also enhanced by glucose. Interestingly, glucose modulated DBMSC expression of genes involved in insulin secretion and prevention of diabetes.

These data show the potentially beneficial effects of glucose on DBMSC functions. Preconditioning of DBMSCs with glucose may therefore be a rational strategy for increasing their therapeutic potential by enhancing their engraftment efficiency. In addition, glucose may program DBMSCs into insulin producing cells with ability to counteract inflammation and infection associated with diabetes. However, future in vitro and in vivo studies are essential to investigate the findings of this study further.

The online version of this article (10.1007/s13770-020-00239-7) contains supplementary material, which is available to authorized users.

• Cellular functions
• Gene expression
• Glucose
• Placental DBMSCs

• CXCR6
• cell recruitment and engraftment
• cell transplantation
• diabetic wound healing
• full thickness excisional splinting wound model
• gene therapy
• mesenchymal stem cells
• molecular signaling
• skin regeneration
• type I (Streptozotocin-induced) and type II (db/db) diabetic mice

• Animals
• Cell Transdifferentiation/genetics
• Chemokine CXCL16/metabolism
• Diabetes Mellitus, Experimental/therapy
• Diabetes Mellitus, Type 1/therapy
• Diabetes Mellitus, Type 2/therapy
• Female
• Genetic Therapy/methods
• Male
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells/metabolism
• Mice
• Mice, Inbred C57BL
• Neovascularization, Physiologic/genetics
• Re-Epithelialization/genetics
• Receptors, CXCR6/genetics
• Receptors, CXCR6/metabolism
• Skin/metabolism
• Transfection
• Transplantation, Homologous/methods
• Treatment Outcome

• Apgar score
• acetylsalicylic acid
• low birth weight
• neonatal intensive care unit
• perinatal death
• pre-eclampsia
• preterm birth

• Abruptio Placentae/chemically induced
• Apgar Score
• Aspirin/administration & dosage
• Aspirin/adverse effects
• Delivery, Obstetric/statistics & numerical data
• Female
• Fetal Growth Retardation/prevention & control
• Humans
• Infant, Low Birth Weight
• Infant, Newborn
• Infant, Newborn, Diseases/chemically induced
• Intensive Care Units, Neonatal/statistics & numerical data
• Perinatal Death/etiology
• Pre-Eclampsia/prevention & control
• Pregnancy
• Pregnancy Outcome
• Premature Birth/prevention & control
• Prenatal Care/methods
• Randomized Controlled Trials as Topic
• Regression Analysis

Placenta-derived mesenchymal stromal cells (MSC) have attracted more attention for their immune modulatory properties and poor immunogenicity, which makes them suitable for allogeneic transplantation. Although MSC isolated from different areas of the placenta share several features, they also present significant biological differences, which might point to distinct clinical applications. Hence, we compared cells from full term placenta distinguishing them on the basis of their origin, either maternal or fetal. We used cells developed by Pluristem LTD: PLacenta expanded mesenchymal-like adherent stromal cells (PLX), maternal-derived cells (PLX-PAD), fetal-derived cells (PLX-R18), and amniotic membrane-derived MSC (hAMSC). We compared immune modulatory properties evaluating effects on T-lymphocyte proliferation, expression of cytotoxicity markers, T-helper and T-regulatory cell polarization, and monocyte differentiation toward antigen presenting cells (APC). Furthermore, we investigated cell immunogenicity. We show that MSCs and MSC-like cells from both fetal and maternal sources present immune modulatory properties versus lymphoid (T cells) and myeloid (APC) cells, whereby fetal-derived cells (PLX-R18 and hAMSC) have a stronger capacity to modulate immune cell proliferation and differentiation. Our results emphasize the importance of understanding the cell origin and characteristics in order to obtain a desired result, such as modulation of the inflammatory response that is critical in fostering regenerative processes.

• PLX: PLacenta expanded mesenchymal-like adherent stromal cells
• amniotic membrane
• human placenta
• immunomodulation
• mesenchymal stromal cells

• Antigen-Presenting Cells/cytology
• Biomarkers/metabolism
• Cell Death
• Cell Differentiation
• Cell Proliferation
• Cytokines/metabolism
• Female
• Fetus/cytology
• Humans
• Immunophenotyping
• Lymphocyte Subsets/cytology
• Lymphocyte Subsets/metabolism
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Monocytes/cytology
• Placenta/cytology
• Pregnancy
• Regenerative Medicine
• T-Lymphocytes/cytology

• Cell based therapy
• Clinical trials
• Conditioned media
• Differentiation potential
• Exosomes
• Hypoxia
• Immunomodulation
• Ischemia
• Placental mesenchymal stem cells
• Pregnancy
• Regenerative medicine
• Secretome
• Stem cells
• Vasculature
• Wound healing

• Animals
• Exosomes/physiology
• Female
• Humans
• Mesenchymal Stem Cells/physiology
• Neovascularization, Physiologic/physiology
• Placenta/physiology
• Pregnancy

• Hofbauer cells
• congenital infection
• immunity
• placenta
• trophoblasts

• Animals
• Biomarkers
• Disease Models, Animal
• Disease Susceptibility
• Female
• Host-Pathogen Interactions
• Humans
• Infectious Disease Transmission, Vertical
• Placenta/immunology
• Placenta/metabolism
• Placenta/virology
• Pregnancy
• Pregnancy Complications, Infectious/metabolism
• Pregnancy Complications, Infectious/virology
• Research
• Virus Diseases/etiology
• Virus Diseases/metabolism
• Virus Diseases/transmission

• Adipose-derived stem cells
• Endometrial injury
• Regeneration
• Stem cell transplantation

• Adipose Tissue/cytology
• Animals
• Cells, Cultured
• Endometrium/injuries
• Endometrium/metabolism
• Female
• Humans
• Infertility/etiology
• Infertility/therapy
• Rats, Sprague-Dawley
• Receptors, Estrogen/metabolism
• Receptors, Progesterone/metabolism
• Stem Cell Transplantation/methods
• Stem Cells/cytology
• Tissue Adhesions/etiology
• Tissue Adhesions/therapy
• Uterine Diseases/etiology
• Uterine Diseases/therapy
• Wounds and Injuries/complications
• Wounds and Injuries/therapy

• Epigenetics
• Methylation
• Peripheral blood
• Placenta
• Preeclampsia

• Bone marrow mesenchymal stem cells
• Electroacupuncture treatment
• Stem cell migration
• Thin endometrium

• Animals
• Bone Marrow Cells/cytology
• Cell Movement
• Electroacupuncture
• Embryo Implantation
• Endometrium/injuries
• Endometrium/pathology
• Endometrium/physiology
• Female
• Fibroblast Growth Factor 2/genetics
• Fibroblast Growth Factor 2/metabolism
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Paracrine Communication
• Rats
• Rats, Sprague-Dawley
• Regeneration
• Uterine Diseases/pathology
• Uterine Diseases/therapy
• Vascular Endothelial Growth Factor A/genetics
• Vascular Endothelial Growth Factor A/metabolism

• China National Natural Science Foundation
• China National Natural Science Foundation

• Alzheimer's disease
• chorion
• hippocampus
• mesenchymal stem cells
• neurodegenerative disorder
• transplantation.

• Cell isolation
• Cell migration
• Fetal human placental stromal cells (f-hPSC)
• Placenta
• Tissue cryopreservation

Since their discovery and characterization, mesenchymal stromal cells (MSC) have been a topic of great interest in regenerative medicine. Over the last 10 years, detailed studies investigated the properties of MSC from perinatal tissues and have indicated that these cells may represent important tools for restoring tissue damage or promoting regeneration and repair of the tissue microenvironment. At first, perinatal tissue-derived MSC drew attention due to their potential differentiation capacities suggested by their early embryological origin. It is nowadays accepted that perinatal tissue-derived MSC are promising for a wide range of regenerative medicine applications because of their unique immune modulatory properties, rather than their differentiation ability. As a matter of fact, the activation and function of various cells of the innate and adaptive immune systems are suppressed and modulated by MSC from different perinatal tissues, such as human term placenta. However, the mechanisms by which they act on immune cells to facilitate tissue repair during pathological processes remain to be thoroughly elucidated to develop safe and efficient therapeutic approaches. In addition to immune modulatory ability, several other peculiar characteristics of placenta MSC, less explored and/or more debated, are being investigated. These include an understanding of the anti-microbial properties and the role of placental MSC in tumor progression. Moreover, a thorough investigation on preparation methods, bioactive factors, mechanisms of action of the cell secretome, and the development of potency assays to predict clinical efficacy of placenta MSC and their products, are necessary to provide a solid basis for their clinical application.

• amniotic membrane
• human term placenta
• immunomodulation
• perinatal tissues
• regenerative medicine