Characterization of Stem Cells and Immune Cells in Preterm and Term Mother’s Milk

Background: Human milk is known to be rich in cellular components, including stem cells and immune cells. However, the dynamics of these cellular components at different lactation stages, and the differences between milk for preterm and term infants, are poorly understood. Research aim: To identify changes in the cellular components of human milk at different lactation stages, and to explore the associations of these changes with maternal and infant characteristics. Methods: Forty mothers of newborns of different gestational ages were enrolled. Colostrum, transitional, and mature milk samples were collected. Stem cell and immune cell molecule markers were detected using flow cytometry. Pluripotent genes (SOX2, NANOG, OCT4, and KLF4) were detected via quantitative real-time PCR. Results: Human milk contained some stem cells but more immune cells. The percentages of hemopoietic stem cells were significantly higher in mature milk than in colostrum, and the percentages of total immune cells were lower in mature milk than in colostrum. The percentages of hemopoietic stem cells in colostrum and transitional milk were influenced by gestational age. Some minor differences in the cell composition of human milk could be explained by maternal body mass index, the mode of delivery, and parity. Conclusion: Our results again confirmed that human milk contains stem cells. Additionally, the percentages of hemopoietic stem cells and major immune cells changed dynamically at different lactation stages and were associated with gestational age at delivery.

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Human milk mycobiota composition: relationship with gestational age, delivery mode, and birth weight

Beneficial Microbes ◽

10.3920/bm2019.0158 ◽

2020 ◽

Vol 11 (2) ◽

pp. 151-162 ◽

Cited By ~ 2

Author(s):

M. Dinleyici ◽

V. Pérez-Brocal ◽

S. Arslanoglu ◽

O. Aydemir ◽

S. Sevuk Ozumut ◽

...

Keyword(s):

Human Milk ◽

Gestational Age ◽

Caesarean Delivery ◽

Abundant Species ◽

Large For Gestational Age ◽

Delivery Mode ◽

Mature Milk ◽

Milk Samples ◽

Delivery Term ◽

Spontaneous Delivery

Intestinal and human milk microbiota studies during infancy have shown variations according to geographical location, delivery mode, gestational age, and mother-related factors during pregnancy. In this study, we performed metagenomic mycobiota analyses of 44 transient and mature human milk among five different groups: mothers of normal spontaneous delivery-term (NS-T), caesarean delivery-term (CS-T), premature (PT), small for gestational age (SGA), and large for gestational age (LGA) infants. Fungi were detected in 80 out of the 88 samples. Regarding the number of observed fungal species, the NS-T group was more homogeneous (less variable) comparing the other groups (P<0.05). In the transient human milk samples, the most abundant species were Saccharomyces cerevisiae (33.3%) and Aspergillus glaucus (27.4%). While A. glaucus (33.7%) was second most abundant species in mature milk, S. cerevisiae disappeared (P<0.01) and Penicillium rubens became the most abundant species (35.5%) (P<0.05). Among the NS-T group, the most abundant species was Malassezia globosa in both transient and mature milk. In contrast, S. cerevisiae was the most abundant species in transient human milk (45.0%) in the CS-T group, but it disappeared in mature milk (P<0.01). In transient milk, M. globosa was only represented 6.0-9.0% of taxa in the PT, SGA, and LGA groups (P<0.05). In transient and mature milk in the PT, SGA and LGA groups, the most abundant species were A. glaucus and P. rubens. In mature milk samples, P. rubens is more abundant in CS-T group, PT group and LGA group, than the NS-T groups (P<0.05 for all). Although fungi constitute only a very small part of the human milk microbiome, we observed some changes that the human milk mycobiota composition varies in caesarean delivery, premature, SGA and LGA groups, comparing the normal spontaneous delivery, as well as differences between transient and mature human milk.

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Relation between Immune cell response and stemness genes expression in breast cancer; A new approach in NANOG gene and Let7-a expression in breast cancer cell lines

Immunopathologia Persa ◽

10.34172/ipp.2020.21 ◽

2020 ◽

Vol 6 (2) ◽

pp. e21-e21

Author(s):

Zeynab Aliyari-Serej ◽

Ayyub Ebrahimi ◽

Tohid Kazemi ◽

Souzan Najafi ◽

Elmira Roshani ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Immune Cells ◽

Immune Cell ◽

Preclinical Study ◽

Breast Cancer Cell Lines ◽

Developmental Behavior ◽

Genes Expression ◽

Nanog Gene ◽

Immune Cell Response

Introduction: Failure and recurrence in breast cancer treatment cause a great obstacle in cancer therapy and identification of cell population named cancer stem cells (CSCs) in the tumor can be led us to define it as target in novel therapeutic strategy. Objectives: The aim of this study is the finding of correlation between stemness and metastatic characteristic, also knowing CSCs as a potential target of therapy because of its developmental behavior and similarities with normal stem cells. Materials and Methods: Here, we focus on the expression of NANOG in breast CSCs, a key molecule in the physiological process of stem cells and the Let-7a that is involved in the differentiation of the cells. Results: In this work, we found that NANOG was highly expressed in SKBR3 and down-regulation of let-7a, as a differentiation miRNA, was found in MDA-MB-468 cells. Conclusion: It will be critical for the developing of effective anti-tumor drugs, utilizing mentioned concepts. Inhibition of NANOG in combination with Let-7a up-regulation can help to decrease the stemness and increase the differentiation of CSCs. The decrease of stemness and increase of differentiation initiate the apoptotic process. So, modification in the mechanism of apoptosis beside anti-cancer drugs provide a good preclinical study goal. However, in order to these drugs become clinical, the problems of their side effects and toxicity must be solved. Differentiation of CSCs provides an optimal condition to activity of immune cells which never let them escape from immune cells by alteration of immunogenicity.

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Quantification of Human Milk Phospholipids: the Effect of Gestational and Lactational Age on Phospholipid Composition

Nutrients ◽

10.3390/nu11020222 ◽

2019 ◽

Vol 11 (2) ◽

pp. 222 ◽

Cited By ~ 10

Author(s):

Ida Ingvordsen Lindahl ◽

Virginia Artegoitia ◽

Eimear Downey ◽

James O’Mahony ◽

Carol-Anne O’Shea ◽

...

Keyword(s):

Human Milk ◽

Gestational Age ◽

Phospholipid Composition ◽

Visual Development ◽

Bioactive Components ◽

Mature Milk ◽

Term Infants ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass ◽

Macro And Micronutrients

Human milk (HM) provides infants with macro- and micronutrients needed for growth and development. Milk phospholipids are important sources of bioactive components, such as long-chain polyunsaturated fatty acids (LC-PUFA) and choline, crucial for neural and visual development. Milk from mothers who have delivered prematurely (<37 weeks) might not meet the nutritional requirements for optimal development and growth. Using liquid chromatography tandem-mass spectrometry, 31 phospholipid (PL) species were quantified for colostrum (<5 days postpartum), transitional (≥5 days and ≤2 weeks) and mature milk (>2 weeks and ≤15 weeks) samples from mothers who had delivered preterm (n = 57) and term infants (n = 22), respectively. Both gestational age and age postpartum affected the PL composition of HM. Significantly higher concentrations (p < 0.05) of phosphatidylcholine (PC), sphingomyelin (SM) and total PL were found in preterm milk throughout lactation, as well as significantly higher concentrations (p < 0.002) of several phosphatidylethanolamine (PE), PC and SM species. Multivariate analysis revealed that PLs containing LC-PUFA contributed highly to the differences in the PL composition of preterm and term colostrum. Differences related to gestation decreased as the milk matured. Thus, gestational age may impact the PL content of colostrum, however this effect of gestation might subside in mature milk.

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Human Milk Virome Analysis: Changing Pattern Regarding Mode of Delivery, Birth Weight, and Lactational Stage

Nutrients ◽

10.3390/nu13061779 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1779

Author(s):

Meltem Dinleyici ◽

Vicente Pérez-Brocal ◽

Sertac Arslanoglu ◽

Ozge Aydemir ◽

Sibel Sevuk Ozumut ◽

...

Keyword(s):

Birth Weight ◽

Human Milk ◽

Vaginal Delivery ◽

Gestational Age ◽

Small For Gestational Age ◽

Mode Of Delivery ◽

Large For Gestational Age ◽

Delivery Mode ◽

Age Group ◽

Spontaneous Vaginal Delivery

The human milk (HM) microbiota is a significant source of microbes that colonize the infant gut early in life. The aim of this study was to compare transient and mature HM virome compositions, and also possible changes related to the mode of delivery, gestational age, and weight for gestational age. Overall, in the 81 samples analyzed in this study, reads matching bacteriophages accounted for 79.5% (mainly Podoviridae, Myoviridae, and Siphoviridae) of the reads, far more abundant than those classified as eukaryotic viruses (20.5%, mainly Herpesviridae). In the whole study group of transient human milk, the most abundant families were Podoviridae and Myoviridae. In mature human milk, Podoviridae decreased, and Siphoviridae became the most abundant family. Bacteriophages were predominant in transient HM samples (98.4% in the normal spontaneous vaginal delivery group, 92.1% in the premature group, 89.9% in the C-section group, and 68.3% in the large for gestational age group), except in the small for gestational age group (only ~45% bacteriophages in transient HM samples). Bacteriophages were also predominant in mature HM; however, they were lower in mature HM than in transient HM (71.7% in the normal spontaneous vaginal delivery group, 60.8% in the C-section group, 56% in the premature group, and 80.6% in the large for gestational age group). Bacteriophages still represented 45% of mature HM in the small for gestational age group. In the transient HM of the normal spontaneous vaginal delivery group, the most abundant family was Podoviridae; however, in mature HM, Podoviridae became less prominent than Siphoviridae. Myoviridae was predominant in both transient and mature HM in the premature group (all C-section), and Podoviridae was predominant in transient HM, while Siphoviridae and Herpesviridae were predominant in mature HM. In the small for gestational age group, the most abundant taxa in transient HM were the family Herpesviridae and a species of the genus Roseolovirus. Bacteriophages constituted the major component of the HM virome, and we showed changes regarding the lactation period, preterm birth, delivery mode, and birth weight. Early in life, the HM virome may influence the composition of an infant’s gut microbiome, which could have short- and long-term health implications. Further longitudinal mother–newborn pair studies are required to understand the effects of these variations on the composition of the HM and the infant gut virome.

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When CAR Meets Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20081825 ◽

2019 ◽

Vol 20 (8) ◽

pp. 1825 ◽

Cited By ~ 1

Author(s):

Jung Min Lee

Keyword(s):

Stem Cells ◽

T Cells ◽

Stem Cell ◽

Cell Therapy ◽

Immune Cells ◽

Pluripotent Stem Cells ◽

Pluripotent Stem Cell ◽

Immune Cell ◽

Embryonic Stem ◽

Lymphoid Cells

The generation of immune cells from human pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) has been of keen interest to regenerative medicine. Pluripotent stem cell-derived immune cells such as natural killer cells, macrophages, and lymphoid cells, especially T cells, can be used in immune cell therapy to treat incurable cancers. Moreover, since the advent of chimeric antigen receptor (CAR) technology, the success of CAR-T cells in the clinic has galvanized new efforts to harness the power of CAR technology to generate CAR-engineered immune cells from pluripotent stem cells. This review provides a summary of pluripotent stem cell-derived immune cells and CAR technology, together with perspectives on combining pluripotent stem-cell derived immune cells and CAR engineering to pave a new way for developing next generation immune cell therapy.

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Identification of sociodemographic and clinical factors associated with the levels of human β-defensin-1 and human β-defensin-2 in the human milk of Han Chinese

British Journal Of Nutrition ◽

10.1017/s0007114513003292 ◽

2013 ◽

Vol 111 (5) ◽

pp. 867-874 ◽

Cited By ~ 14

Author(s):

Xiao-Fang Wang ◽

Rui-Ming Cao ◽

Jing Li ◽

Jing Wu ◽

Sheng-Mei Wu ◽

...

Keyword(s):

Human Milk ◽

Respiratory Infection ◽

Strong Association ◽

Mode Of Delivery ◽

Multivariable Analysis ◽

Han Chinese ◽

Mature Milk ◽

Protective Function ◽

Upper Respiratory Infection ◽

Upper Respiratory

Human milk provides infants with various immune molecules. The objective of the present study was to measure human β-defensin-1 (hBD-1) and human β-defensin-2 (hBD-2) levels in the colostrum and mature milk of healthy Han Chinese, to identify factors regulating milk hBD-1 and hBD-2 expression and to explore the potential protective effect of milk hBD-1 and hBD-2 on infants. A total of 100 mothers and their babies were recruited into the study. Sociodemographic characteristics and other factors were obtained by a questionnaire. Babies were followed up for a period of 6 months. Colostrum samples (n100) and mature milk samples (n82) were collected by hand expression. The hBD-1 and hBD-2 concentrations were measured by ELISA. The hBD-1 and hBD-2 levels differed in the colostrum and mature milk. In the colostrum, the concentration ranges of hBD-1 and hBD-2 were 1·04–12·81 μg/ml and 0·31–19·12 ng/ml, respectively. In mature milk, the hBD-1 and hBD-2 levels were 1·03–31·76 ng/ml and 52·65–182·29 pg/ml, respectively. Several independent factors influence their production. The multivariable analysis showed a strong association between pre-pregnancy BMI and hBD-1 levels in the colostrum (P= 0·001), mode of delivery was significantly associated with hBD-2 levels in the colostrum (P= 0·006) and gestational age was significantly associated with hBD-1 levels in mature milk (P= 0·010). During the first 6 months of life, the incidence rate of upper respiratory infection was found to be less in the high-colostrum hBD-1 group than in the low-colostrum hBD-1 group (χ2= 4·995,P= 0·025). The present study suggested that the abundance of hBD-1 in the colostrum may have a protective function against upper respiratory infection for infants younger than 6 months.

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The Relevance of Fetal Abdominal Subcutaneous Tissue Recording in Predicting Perinatal Outcome of GDM Pregnancies: A Retrospective Study

Journal of Clinical Medicine ◽

10.3390/jcm9103375 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3375

Author(s):

Friederike Weschenfelder ◽

Nadin Baum ◽

Thomas Lehmann ◽

Ekkehard Schleußner ◽

Tanja Groten

Keyword(s):

Gestational Age ◽

Predictive Power ◽

Neonatal Outcome ◽

Subcutaneous Tissue ◽

Mode Of Delivery ◽

Abdominal Circumference ◽

Large For Gestational Age ◽

Maternal Body Mass Index ◽

Clinical Parameters ◽

Ultrasound Parameters

Guidelines on the management of gestational diabetes (GDM) instruct physicians to involve ultrasound-based monitoring of fetal growth in addition to blood glucose. So far, glucose control besides clinical parameters like maternal body mass index (BMI) and gestational weight gain have been shown to predict neonatal outcome. We aimed to evaluate the discriminative ability of fetal abdominal subcutaneous tissue (FAST) in addition to standard ultrasound parameters like abdominal circumference (AC) and estimated fetal weight (EFW) for perinatal complications like large for gestational age (LGA), hypoglycemia, hyperbilirubinemia, mode of delivery and admission to neonatal intensive care unit (NICU). Ultrasound data and neonatal outcome was collected of 805 GDM cases from 2012 to 2016: 3205 FAST, 3195 AC-measurements and 3190 EFW calculations were included. AC, EFW and FAST increased linear with gestational age. Combining ultrasound and clinical parameters improved predictive power for LGA. In the subgroup where fetuses grow with an AC > 75th additional adding of FAST to standard ultrasound parameters increased predictive power for hypoglycemia. Our results confirm inclusion of ultrasound parameters to be beneficial in monitoring GDM pregnancies. Additional FAST determination revealed to be of potential clinical relevance in the subgroup AC > 75th percentile.

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Adaptive and Innate Immune Cell Responses in Tendons and Lymph Nodes After Tendon Injury and Repair

10.1101/658310 ◽

2019 ◽

Author(s):

Andrew C Noah ◽

Thomas M Li ◽

Leandro M Martinez ◽

Susumu Wada ◽

Jacob B Swanson ◽

...

Keyword(s):

Immune System ◽

Immune Cells ◽

Immune Cell ◽

Tendon Healing ◽

Tendon Injury ◽

Tendon Injuries ◽

Innate Immune ◽

Adaptive Immune ◽

Immune Cell Response ◽

Cellular Components

AbstractTendon injuries are a common clinical condition with limited treatment options. The cellular components of the innate system, such as neutrophils and macrophages, have been well studied in tendon injuries. However the adaptive immune system, comprised of specialized lymphocytes, plays an important role in orchestrating the healing of numerous tissues but less is known about these cells in tendon healing. To gain a greater understanding of the biological processes that regulate tendon healing, we sought to determine how the cellular components of the adaptive and innate immune system respond to a tendon injury using two-month old male mice. We determined that the lymphatic vasculature is present in the epitenon and superficial regions of Achilles tendons. We then created an acute Achilles tenotomy followed by repair, and collected tendons and draining lymph nodes one, two, and four weeks after injury. Using flow cytometry and histology, after tendon injury we observed a robust adaptive immune cell response that followed an initial innate immune cell response. There was an accumulation of monocytes, neutrophils, and macrophages one week after injury that declined thereafter. Dendritic cells and CD4+ T cells peaked two weeks after injury, while B cells and CD8+ T cells progressively increased over time. In parallel, immune cells of the draining popliteal lymph node demonstrated a similarly coordinated response to the injury. These results suggest that there is an adaptive immune response to tendon injury and adaptive immune cells may play a role in regulating tendon healing.

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Concentration of Lactoferrin in Human Milk and Its Variation during Lactation in Different Chinese Populations

Nutrients ◽

10.3390/nu10091235 ◽

2018 ◽

Vol 10 (9) ◽

pp. 1235 ◽

Cited By ~ 12

Author(s):

Zhenyu Yang ◽

Rulan Jiang ◽

Qi Chen ◽

Jie Wang ◽

Yifan Duan ◽

...

Keyword(s):

Human Milk ◽

Dynamic Change ◽

Mode Of Delivery ◽

Cross Sectional Study ◽

Albumin Concentration ◽

Mature Milk ◽

Cross Sectional ◽

Maternal Characteristics ◽

Chinese Populations ◽

Geographical Regions

Background: Lactoferrin (Lf) is a multifunctional protein and one of the most abundant proteins in human milk. Various factors may affect its concentration in human milk, such as stage of lactation, ethnicity, and diet. Objectives: The objectives of the present study were to examine the dynamic change in milk Lf throughout the course of lactation and explore factors associated with milk Lf concentrations in various Chinese populations. Methods: This investigation was a part of a large cross-sectional study conducted in 11 provinces/autonomous regions/municipalities (Beijing, Gansu, Guangdong, Guangxi, Heilongjiang, Inner Mongolia, Shandong, Shanghai, Xinjiang, Yunnan, and Zhejiang) across China between 2011 and 2013. Lactating women (n = 6481) within 0–330 days postpartum were recruited in the original study. A sub-sample of 824 women was randomly selected, and milk Lf concentrations were determined by UPLC/MS. Results: The Lf concentration in milk from women delivering at term was 3.16 g/L, 1.73 g/L and 0.90 g/L for colostrum, transitional milk, and mature milk, respectively. Lf concentrations differed significantly between stages of lactation (colostrum vs. transitional milk, colostrum vs. mature milk, transitional milk vs. mature milk, all p < 0.001). Maternal BMI, age, mode of delivery, parturition, protein intake, and serum albumin concentration were not correlated with milk Lf concentration. However, milk Lf concentrations varied among different geographical regions (Guangdong (1.91 g/L) vs. Heilongjiang (1.44 g/L), p = 0.037; Guangdong (1.91 g/L) vs. Gansu (1.43 g/L), p = 0.041) and ethnicities (Dai (1.80 g/L) vs. Tibetan (0.99 g/L), p = 0.007; Han (1.62 g/L) vs. Tibetan (0.99 g/L), p = 0.002) in China. Conclusions: The concentration of Lf in human milk changes dynamically throughout lactation. Few maternal characteristics affect the milk Lf concentration, but it varies across different geographical regions and ethnicities in China.

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Intestinal Stem Cells and Immune Cell Relationships: Potential Therapeutic Targets for Inflammatory Bowel Diseases

Frontiers in Immunology ◽

10.3389/fimmu.2020.623691 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qihang Hou ◽

Jingxi Huang ◽

Hammed Ayansola ◽

Hori Masatoshi ◽

Bingkun Zhang

Keyword(s):

Stem Cells ◽

T Cells ◽

Dendritic Cells ◽

Immune Cells ◽

Immune Cell ◽

Clinical Symptoms ◽

Chronic Inflammatory Disease ◽

Intestinal Stem Cells ◽

Inflammatory Bowel

The mammalian intestine is the largest immune organ that contains the intestinal stem cells (ISC), differentiated epithelial cells (enterocytes, Paneth cells, goblet cells, tuft cells, etc.), and gut resident-immune cells (T cells, B cells, dendritic cells, innate lymphoid cell, etc.). Inflammatory bowel disease (IBD), a chronic inflammatory disease characterized by mucosa damage and inflammation, threatens the integrity of the intestine. The continuous renewal and repair of intestinal mucosal epithelium after injury depend on ISCs. Inflamed mucosa healing could be a new target for the improvement of clinical symptoms, disease recurrence, and resection-free survival in IBD treated patients. The knowledge about the connections between ISC and immune cells is expanding with the development of in vitro intestinal organoid culture and single-cell RNA sequencing technology. Recent findings implicate that immune cells such as T cells, ILCs, dendritic cells, and macrophages and cytokines secreted by these cells are critical in the regeneration of ISCs and intestinal epithelium. Transplantation of ISC to the inflamed mucosa may be a new therapeutic approach to reconstruct the epithelial barrier in IBD. Considering the links between ISC and immune cells, we predict that the integration of biological agents and ISC transplantation will revolutionize the future therapy of IBD patients.

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