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Faa G, Pichiri G, Coni P, Dessì A, Fraschini M, Fanos V. They will be famous: Multipotent stem cells in breast milk. World J Clin Pediatr 2025; 14:101080. [PMID: 40491730 PMCID: PMC11947875 DOI: 10.5409/wjcp.v14.i2.101080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 01/20/2025] [Accepted: 02/12/2025] [Indexed: 03/18/2025] Open
Abstract
Breast milk represents the gold standard for neonatal nutrition, especially for preterm and term infants with a low birthweight. This awareness is based not only on the nutritional properties of human milk, which is specifically designed for the growth of humans but also on breast milk's non-nutritional properties, such as protection against infection. In fact, breast milk should be considered a heterogeneous ecosystem, including a wide range of cells in addition to those involved in immune function; growth factors, such as vascular endothelial growth factor; multiple noncoding microRNAs; immune cells; epithelial cells and multipotent mesenchymal stem cells. This recent identification of a pool of progenitor stem cells in human milk is the driving force behind the growing research aimed at identifying the nature of these stem/progenitor cells and their sources.
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Affiliation(s)
- Gavino Faa
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari 09100, Sardegna, Italy
| | - Giuseppina Pichiri
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari 09100, Sardegna, Italy
| | - Pierpaolo Coni
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari 09100, Sardegna, Italy
| | - Angelica Dessì
- Department of Surgical Sciences, University of Cagliari, Cagliari 09100, Sardegna, Italy
| | - Matteo Fraschini
- Department of Ingegneria Elettrica ed Elettronica, University of Cagliari, Cagliari 09100, Sardegna, Italy
| | - Vassilios Fanos
- Department of Surgical Sciences, AOU and University of Cagliari, Neonatal Intensive Care Unit, Monserrato 09042, Italy
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Marquez-Curtis LA, Elliott JAW. Mesenchymal stromal cells derived from various tissues: Biological, clinical and cryopreservation aspects: Update from 2015 review. Cryobiology 2024; 115:104856. [PMID: 38340887 DOI: 10.1016/j.cryobiol.2024.104856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 01/26/2024] [Accepted: 01/30/2024] [Indexed: 02/12/2024]
Abstract
Mesenchymal stromal cells (MSCs) have become one of the most investigated and applied cells for cellular therapy and regenerative medicine. In this update of our review published in 2015, we show that studies continue to abound regarding the characterization of MSCs to distinguish them from other similar cell types, the discovery of new tissue sources of MSCs, and the confirmation of their properties and functions that render them suitable as a therapeutic. Because cryopreservation is widely recognized as the only technology that would enable the on-demand availability of MSCs, here we show that although the traditional method of cryopreserving cells by slow cooling in the presence of 10% dimethyl sulfoxide (Me2SO) continues to be used by many, several novel MSC cryopreservation approaches have emerged. As in our previous review, we conclude from these recent reports that viable and functional MSCs from diverse tissues can be recovered after cryopreservation using a variety of cryoprotectants, freezing protocols, storage temperatures, and periods of storage. We also show that for logistical reasons there are now more studies devoted to the cryopreservation of tissues from which MSCs are derived. A new topic included in this review covers the application in COVID-19 of MSCs arising from their immunomodulatory and antiviral properties. Due to the inherent heterogeneity in MSC populations from different sources there is still no standardized procedure for their isolation, identification, functional characterization, cryopreservation, and route of administration, and not likely to be a "one-size-fits-all" approach in their applications in cell-based therapy and regenerative medicine.
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Affiliation(s)
- Leah A Marquez-Curtis
- Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada, T6G 1H9; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada, T6G 1C9
| | - Janet A W Elliott
- Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada, T6G 1H9; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada, T6G 1C9.
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Neville MC, Demerath EW, Hahn-Holbrook J, Hovey RC, Martin-Carli J, McGuire MA, Newton ER, Rasmussen KM, Rudolph MC, Raiten DJ. Parental factors that impact the ecology of human mammary development, milk secretion, and milk composition-a report from "Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)" Working Group 1. Am J Clin Nutr 2023; 117 Suppl 1:S11-S27. [PMID: 37173058 PMCID: PMC10232333 DOI: 10.1016/j.ajcnut.2022.11.026] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 11/22/2022] [Accepted: 11/29/2022] [Indexed: 05/15/2023] Open
Abstract
The goal of Working Group 1 in the Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN) Project was to outline factors influencing biological processes governing human milk secretion and to evaluate our current knowledge of these processes. Many factors regulate mammary gland development in utero, during puberty, in pregnancy, through secretory activation, and at weaning. These factors include breast anatomy, breast vasculature, diet, and the lactating parent's hormonal milieu including estrogen, progesterone, placental lactogen, cortisol, prolactin, and growth hormone. We examine the effects of time of day and postpartum interval on milk secretion, along with the role and mechanisms of lactating parent-infant interactions on milk secretion and bonding, with particular attention to the actions of oxytocin on the mammary gland and the pleasure systems in the brain. We then consider the potential effects of clinical conditions including infection, pre-eclampsia, preterm birth, cardiovascular health, inflammatory states, mastitis, and particularly, gestational diabetes and obesity. Although we know a great deal about the transporter systems by which zinc and calcium pass from the blood stream into milk, the interactions and cellular localization of transporters that carry substrates such as glucose, amino acids, copper, and the many other trace metals present in human milk across plasma and intracellular membranes require more research. We pose the question of how cultured mammary alveolar cells and animal models can help answer lingering questions about the mechanisms and regulation of human milk secretion. We raise questions about the role of the lactating parent and the infant microbiome and the immune system during breast development, secretion of immune molecules into milk, and protection of the breast from pathogens. Finally, we consider the effect of medications, recreational and illicit drugs, pesticides, and endocrine-disrupting chemicals on milk secretion and composition, emphasizing that this area needs much more research attention.
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Affiliation(s)
- Margaret C Neville
- Department of Obstetrics and Gynecology, University of Colorado, Aurora, CO, USA.
| | - Ellen W Demerath
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, United States
| | - Jennifer Hahn-Holbrook
- Department of Psychological Sciences, University of California Merced, Merced, CA, United States
| | - Russell C Hovey
- Department of Animal Science, University of California Davis, Davis, CA, United States
| | - Jayne Martin-Carli
- Department of Pediatrics, University of Colorado, Aurora, CO, United States
| | - Mark A McGuire
- Idaho Agricultural Experiment Station, University of Idaho, Moscow, ID, United States
| | - Edward R Newton
- Department of Obstetrics and Gynecology, Brody School of Medicine, East Carolina University, Greenville, NC, United States
| | - Kathleen M Rasmussen
- Nancy Schlegel Meinig Professor of Maternal and Child Nutrition, Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States
| | - Michael C Rudolph
- The University of Oklahoma Health Science Center, Oklahoma City, OK, United States
| | - Daniel J Raiten
- Pediatric Growth and Nutrition Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
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Aldè M, Di Berardino F, Ambrosetti U, Barozzi S, Piatti G, Consonni D, Zanetti D, Pignataro L, Cantarella G. Hearing outcomes in preterm infants with confirmed hearing loss. Int J Pediatr Otorhinolaryngol 2022; 161:111262. [PMID: 35947927 DOI: 10.1016/j.ijporl.2022.111262] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 07/29/2022] [Indexed: 11/19/2022]
Abstract
OBJECTIVES Premature infants are at high risk for hearing loss (HL). The aim of the present study is to assess the frequency of preterm infants affected by HL who experience hearing improvement over months and evaluate possible factors associated with hearing changes. METHODS This retrospective study was conducted in a third-level referral audiologic center. Preterm infants with a confirmed diagnosis of sensorineural HL within the first 3 months of life were reassessed at 18 months corrected age using the click-evoked auditory brainstem response between January 1, 2012, and June 30, 2020. The frequency of hearing improvement and associations between possible risk factors and hearing changes were evaluated. RESULTS A total of 138 preterm infants (71 male and 67 female; mean gestational age: 30+2 weeks) were assessed. The percentages of hearing improvement and hearing threshold normalization were 58.7% (81/138) and 35.5% (49/138), respectively. We observed a higher frequency of hearing improvement among preterm infants who had received exclusive breastfeeding or mixed feeding compared with those who had received exclusive infant formula (80% versus 29.3%, P < 0.001). CONCLUSION This study confirms the importance of performing a long audiological follow-up and postponing the indication for cochlear implantation in children with a history of preterm birth. Because of the expression of mesenchymal stem cells and high total antioxidant capacity, breast milk might play a protective role in the auditory system of preterm infants. These findings could have important implications for clinical practice, positively impacting the long-term hearing outcomes of preterm infants.
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Affiliation(s)
- Mirko Aldè
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Audiology Unit, Department of Specialist Surgical Sciences, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Federica Di Berardino
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Audiology Unit, Department of Specialist Surgical Sciences, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Umberto Ambrosetti
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
| | - Stefania Barozzi
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
| | - Gioia Piatti
- Department of Pathophysiology and Transplantation, University of Milan and Unit of Bronchopneumology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Dario Consonni
- Epidemiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Diego Zanetti
- Audiology Unit, Department of Specialist Surgical Sciences, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Lorenzo Pignataro
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Otolaryngology Unit, Department of Specialist Surgical Sciences, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Giovanna Cantarella
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Otolaryngology Unit, Department of Specialist Surgical Sciences, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
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5
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Lokossou GAG, Kouakanou L, Schumacher A, Zenclussen AC. Human Breast Milk: From Food to Active Immune Response With Disease Protection in Infants and Mothers. Front Immunol 2022; 13:849012. [PMID: 35450064 PMCID: PMC9016618 DOI: 10.3389/fimmu.2022.849012] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 03/07/2022] [Indexed: 12/29/2022] Open
Abstract
Breastfeeding is associated with long-term wellbeing including low risks of infectious diseases and non-communicable diseases such as asthma, cancer, autoimmune diseases and obesity during childhood. In recent years, important advances have been made in understanding the human breast milk (HBM) composition. Breast milk components such as, non-immune and immune cells and bioactive molecules, namely, cytokines/chemokines, lipids, hormones, and enzymes reportedly play many roles in breastfed newborns and in mothers, by diseases protection and shaping the immune system of the newborn. Bioactive components in HBM are also involved in tolerance and appropriate inflammatory response of breastfed infants if necessary. This review summarizes the current literature on the relationship between mother and her infant through breast milk with regard to disease protection. We will shed some light on the mechanisms underlying the roles of breast milk components in the maintenance of health of both child and mother.
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Affiliation(s)
- Gatien A. G. Lokossou
- Research Unit in Applied Microbiology and Pharmacology of Natural Substances, Polytechnic School of Abomey-Calavi, Department Human Biology Engineering, University of Abomey-Calavi, Abomey-Calavi, Benin
| | - Léonce Kouakanou
- Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, United States
| | - Anne Schumacher
- Department of Environmental Immunology, Helmholtz Centre for Environmental Research and Perinatal Immunology, Saxonian Incubator for Clinical Translation, Medical Faculty, University of Leipzig, Leipzig, Germany
| | - Ana C. Zenclussen
- Department of Environmental Immunology, Helmholtz Centre for Environmental Research and Perinatal Immunology, Saxonian Incubator for Clinical Translation, Medical Faculty, University of Leipzig, Leipzig, Germany
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Mane S, Taneja S, Madala JS, Agarkhedkar S, Khetan M. Study of Stem Cells in Human Milk. Cureus 2022; 14:e23701. [PMID: 35505743 PMCID: PMC9056078 DOI: 10.7759/cureus.23701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/31/2022] [Indexed: 11/05/2022] Open
Abstract
Stem cells are cells that have the ability to self-renew into an undifferentiated cell state, which can further delineate into distinct cell types. There are various sources of stem cells in the human body; some of them include cord blood, placental tissue, bone marrow, adipose tissue, dental pulp, etc. Breast milk could become an important source of stem cells in the near future because of its non-invasive isolation technique. Based on this nature, this study was conducted to isolate stem cells from breast milk and to show further potential implications of these cells. The total number of cells isolated from the milk ranged from 1.5 × 105 cells to 3 × 105 cells. As there was prolongation in the lactation period, the number of cells in the milk lowered significantly. There was no significant difference in the cell count in various gestational age groups. The cytochemistry analysis of these cells with their specific cell markers confirmed the presence of a homogenous population of mesenchymal stem cells. Further differentiation of these breast milk stem cell analyses showed transformation into adipocytes, chondrocytes, and osteoblasts in different culture mediums. So the presence of mesenchymal stem cells in human milk, which are multipotent in nature, makes it an important source of stem cells for further regenerative therapies, tissue culture techniques, and gene therapies. Due to this nature, these cells can be redirected to produce various tissues in the human body.
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Valatkaitė E, Baušytė R, Vitkevičienė A, Ramašauskaitė D, Navakauskienė R. Decidualization Potency and Epigenetic Changes in Human Endometrial Origin Stem Cells During Propagation. Front Cell Dev Biol 2021; 9:765265. [PMID: 34869358 PMCID: PMC8640123 DOI: 10.3389/fcell.2021.765265] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 10/18/2021] [Indexed: 01/10/2023] Open
Abstract
Human endometrium derived mesenchymal stem cells (hEndSCs) offer a great promise for regenerative medicine and reproductive system disorders treatment methods based on cell therapy due to their broad differentiation potential and highly efficient proliferation. In our study, we investigated the characteristics of hEndSCs that were isolated from two sources: endometrium and menstrual blood, which both contain endometrial origin stem cells. Changes in gene and protein expression levels during long-term cultivation and decidualization potential were examined in endometrial stem cells (EndSCs) and menstrual blood stem cells (MenSCs). The decidualization process was induced on early and late passages of hEndSCs using dibutyryl cyclic-AMP (db-cAMP) and medroxyprogesterone acetate (MPA) agents. We demonstrated that after long-term cultivation of hEndSCs the expression of typical mesenchymal stromal cell surface markers such as CD44, CD73, CD90, CD105 and perivascular marker CD146 remains at a similar level throughout long-term cultivation. Additionally, hematopoietic and endothelial markers CD34, CD45 were also tested, they were negative in all cases. Analyzed stem cells gene markers, such as OCT4, SOX2, NANOG, KLF4, showed similar expression in all passages of hEndSCs. RT-qPCR results demonstrated that the expression of cell cycle control associated genes - CDK2, CCNA2, CCNE2, p21, p53 and Rb, among all groups was very similar. Expression of genes associated with senescence (ATM, JUND, TOP2A, MYC) was maintained at a similar level throughout passaging. In addition, Western blot analysis was used to assess changes in proteins’ levels associated to epigenetics (EZH2, SUZ12, H3K27me3) and cell cycle control (cyclinE1, p53) during long-term cultivation. The levels of proteins associated with epigenetic changes were fluctuated slightly depending on the patient. Also, we demonstrated that in all induced hEndSCs the expression of decidualization markers Prolactin (PRL), IGFBP1 and WNT4 was upregulated. In conclusion, we demonstrated successful decidualization of stem cells derived from two reproductive system resources: endometrium and menstrual blood by using db-cAMP and MPA regardless of the length of the stem cell passaging. According these findings, we suppose that endometrium derived stem cells and menstrual blood derived stem cells could have a potency not only for endometrium tissue regeneration, but could also become a successful therapy for reproductive system disorders, including infertility or recurrent pregnancy loss.
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Affiliation(s)
- Elvina Valatkaitė
- Department of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | - Raminta Baušytė
- Department of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania.,Centre of Obstetrics and Gynaecology of the Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Aida Vitkevičienė
- Department of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | - Diana Ramašauskaitė
- Centre of Obstetrics and Gynaecology of the Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Rūta Navakauskienė
- Department of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania
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Vizzari G, Morniroli D, Ceroni F, Verduci E, Consales A, Colombo L, Cerasani J, Mosca F, Giannì ML. Human Milk, More Than Simple Nourishment. CHILDREN (BASEL, SWITZERLAND) 2021; 8:863. [PMID: 34682128 PMCID: PMC8535116 DOI: 10.3390/children8100863] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/18/2021] [Accepted: 09/19/2021] [Indexed: 12/24/2022]
Abstract
Human breast milk not only has nutritional properties but also holds a functional role. It contains various bioactive factors (lactoferrin, lysozyme, leukocytes, immunoglobulins, cytokines, hormones, human milk oligosaccharides, microbiome, microRNAs and stem cells) shown to contribute to several short- and long-term health outcomes. Some of these factors appear to be involved in the infant's neuro-cognitive development, anti-oncogenic processes, cellular communication and differentiation. Furthermore, breast milk is increasingly recognized to have dynamic characteristics and to play a fundamental role in the cross-talking mother-neonate. This narrative review aims to provide a summary and an update on these bioactive substances, exploring their functions mainly on immunomodulation, microbiome and virome development. Although the knowledge about breast milk potentiality has significantly improved, leading to discovering unexpected functions, the exact mechanisms with which breast milk exercises its bioactivity have not been completely clarified. This can represent a fertile ground for exploring and understanding the complexity behind these functional elements to develop new therapeutic strategies.
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Affiliation(s)
- Giulia Vizzari
- Department of Clinical Sciences and Community Health, University of Milan, Via Commenda 19, 20122 Milan, Italy; (G.V.); (D.M.); (F.C.); (A.C.); (J.C.); (F.M.)
| | - Daniela Morniroli
- Department of Clinical Sciences and Community Health, University of Milan, Via Commenda 19, 20122 Milan, Italy; (G.V.); (D.M.); (F.C.); (A.C.); (J.C.); (F.M.)
| | - Federica Ceroni
- Department of Clinical Sciences and Community Health, University of Milan, Via Commenda 19, 20122 Milan, Italy; (G.V.); (D.M.); (F.C.); (A.C.); (J.C.); (F.M.)
| | - Elvira Verduci
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, 20154 Milan, Italy;
- Department of Health Sciences, University of Milan, 20154 Milan, Italy
| | - Alessandra Consales
- Department of Clinical Sciences and Community Health, University of Milan, Via Commenda 19, 20122 Milan, Italy; (G.V.); (D.M.); (F.C.); (A.C.); (J.C.); (F.M.)
| | - Lorenzo Colombo
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico NICU, Via Commenda 12, 20122 Milan, Italy;
| | - Jacopo Cerasani
- Department of Clinical Sciences and Community Health, University of Milan, Via Commenda 19, 20122 Milan, Italy; (G.V.); (D.M.); (F.C.); (A.C.); (J.C.); (F.M.)
| | - Fabio Mosca
- Department of Clinical Sciences and Community Health, University of Milan, Via Commenda 19, 20122 Milan, Italy; (G.V.); (D.M.); (F.C.); (A.C.); (J.C.); (F.M.)
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico NICU, Via Commenda 12, 20122 Milan, Italy;
| | - Maria Lorella Giannì
- Department of Clinical Sciences and Community Health, University of Milan, Via Commenda 19, 20122 Milan, Italy; (G.V.); (D.M.); (F.C.); (A.C.); (J.C.); (F.M.)
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico NICU, Via Commenda 12, 20122 Milan, Italy;
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Abstract
PURPOSE OF REVIEW Breast milk (BM) is a peculiar fluid owing unique properties and resulting the ideal food during early neonatal period. As widely known, it can improve the outcome of both neonate and lactating mother, influencing their whole life. BM is characterized by several beneficial components; among these, a great role is played by BM own and specific microbiome, deeply investigated in many studies. Moreover, the use of metabolomics in BM analysis allowed a better characterization of its metabolic pathways that vary according to lactation stage and neonatal gestational age. The aim of this review is to describe growth factors, cytokines, immunity mediators, and stem cells (SCs) contained in BM and investigate their functions and effects on neonatal outcome, especially focusing on immuno- and neurodevelopment. RECENT FINDINGS We evaluated recent and updated literature on this field. The article that we analyzed to write this review have been found in MEDLINE using breast milk-derived stem cells, biofactors, growth factors, breastfeeding-related outcomes, neurodevelopment, and neonatal immunological system as keywords. Discovering and characterizing BM components could result very useful to clarify the pathophysiology of their influence on neonatal growth and even to improve artificial formulations' composition. Moreover, since SCs abilities and their involvement in the development of several diseases, they could help to discover specific targets for new therapies. It could be useful to characterize BM-derived SC markers, properties, and variations during lactation stages, to understand their potential role in therapeutic applications, since they could be noninvasively isolated from BM. More studies will help to describe more in detail the characteristics of mother-to-child communication through breastfeeding and its potential role in the next future.
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10
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Amniotic fluid and breast milk: a rationale for breast milk stem cell therapy in neonatal diseases. Pediatr Surg Int 2020; 36:999-1007. [PMID: 32671487 DOI: 10.1007/s00383-020-04710-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/30/2020] [Indexed: 12/18/2022]
Abstract
Amniotic fluid and breast milk play important roles in structural development throughout fetal growth and infancy. Given their significance in physical maturation, many studies have investigated the therapeutic and protective roles of amniotic fluid and breast milk in neonatal diseases. Of particular interest to researchers are stem cells found in the two fluids. These stem cells have been investigated due to their ability to self-replicate, differentiate, reduce tissue damage, and their expression of pluripotent markers. While amniotic fluid stem cells have received some attention regarding their ability to treat neonatal diseases, breast milk stem cells have not been investigated to the same extent given the recency of their discovery. The purpose of this review is to compare the functions of amniotic fluid, breast milk, and their stem cells to provide a rationale for the use of breast milk stem cells as a therapy for neonatal diseases. Breast milk stem cells present as an important tool for treating neonatal diseases given their ability to reduce inflammation and tissue damage, as well as their multilineage differentiation potential, easy accessibility, and ability to be used in disease modelling.
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11
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Marquez-Curtis LA, Dorobantu LS, Sauvageau D, Elliott JAW. Cryopreservation of swine colostrum-derived cells. Cryobiology 2020; 97:168-178. [PMID: 32464145 DOI: 10.1016/j.cryobiol.2020.05.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 05/19/2020] [Accepted: 05/21/2020] [Indexed: 12/24/2022]
Abstract
Mesenchymal stromal cells (MSCs) have been demonstrated to possess anti-inflammatory and antimicrobial properties and are of interest in biotechnologies that will require cryopreservation. Recently, MSC-like cells were isolated from colostrum and milk. We used an interrupted slow freezing procedure to examine cryoinjury incurred during slow cooling and rapid cooling of MSC-like cells from swine colostrum. Cells were loaded with either dimethyl sulfoxide (Me2SO) or glycerol, cooled to a nucleation temperature, ice-nucleated, and further cooled at 1 °C/min. At several temperatures along the cooling path, cells were either thawed directly, or plunged into liquid nitrogen for storage and later thawed. The pattern of direct-thaw and plunge-thaw responses was used to guide optimization of cryopreservation protocol parameters. We found that both 5% Me2SO (0.65 M, loaded for 15 min on ice) or 5% glycerol (0.55 M, loaded for 1 h at room temperature) yielded cells with high post-thaw membrane integrity when cells were cooled to at least -30 °C before being plunged into, and stored in, liquid nitrogen. Cells cultured post-thaw exhibited osteogenic differentiation similar to fresh unfrozen control. Fresh and cryopreserved MSC-like cells demonstrated antimicrobial activity against S. aureus. Also, the antimicrobial activity of cell-conditioned media was higher when both fresh and cryopreserved MSC-like cells were pre-exposed to S. aureus. Thus, we were able to demonstrate cryopreservation of colostrum-derived MSC-like cells using Me2SO or glycerol, and show that both cryoprotectants yield highly viable cells with osteogenic potential, but that cells cryopreserved with glycerol retain higher antimicrobial activity post-thaw.
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Affiliation(s)
- Leah A Marquez-Curtis
- Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
| | - Loredana S Dorobantu
- Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada
| | - Dominic Sauvageau
- Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada
| | - Janet A W Elliott
- Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
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12
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Li S, Zhang L, Zhou Q, Jiang S, Yang Y, Cao Y. Characterization of Stem Cells and Immune Cells in Preterm and Term Mother's Milk. J Hum Lact 2019; 35:528-534. [PMID: 31026180 DOI: 10.1177/0890334419838986] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
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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Affiliation(s)
- Shujuan Li
- 1 Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China
| | - Lan Zhang
- 1 Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China
| | - Qi Zhou
- 1 Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China
| | - Siyuan Jiang
- 1 Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China
| | - Yi Yang
- 2 NHC Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China.,3 Pediatric Institute, Children's Hospital of Fudan University, Shanghai, China
| | - Yun Cao
- 1 Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China
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Fernández L, Ruiz L, Jara J, Orgaz B, Rodríguez JM. Strategies for the Preservation, Restoration and Modulation of the Human Milk Microbiota. Implications for Human Milk Banks and Neonatal Intensive Care Units. Front Microbiol 2018; 9:2676. [PMID: 30473683 PMCID: PMC6237971 DOI: 10.3389/fmicb.2018.02676] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 10/19/2018] [Indexed: 12/11/2022] Open
Abstract
Studies carried in the last years have revealed that human milk contains a site-specific microbiota and constitutes a source of potentially beneficial bacteria to the infant gut. Once in the infant gut, these bacteria contribute to the assembly of a physiological gut microbiota and may play several functions, contributing to infant metabolism, protection against infections, immunomodulation or neuromodulation. Many preterm neonates are fed with pasteurized donor's human milk (DHM) or formula and, therefore, are devoid of contact with human milk microbes. As a consequence, new strategies are required to allow the exposition of a higher number of preterm infants to the human milk microbiota early in life. The first strategy would be to promote and to increase the use of own mother's milk (OMM) in Neonatal Intensive Care Units (NICUs). Even small quantities of OMM can be very valuable since they would be added to DHM in order to microbiologically "customize" it. When OMM is not available, a better screening of donor women, including routine cytomegalovirus (CMV) screening of milk, may help to avoid the pasteurization of the milk provided by, at least, a relevant proportion of donors. Finally, when pasteurized DHM or formula are the only feeding option, their supplementation with probiotic bacteria isolated from human milk, such as lactic acid bacteria or bifidobacteria, may be an alternative to try to restore a human milk-like microbiota before feeding the babies. In the future, the design of human milk bacterial consortia (minimal human milk microbiotas), including well characterized strains representative of a healthy human milk microbiota, may be an attractive strategy to provide a complex mix of strains specifically tailored to this target population.
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Affiliation(s)
- Leónides Fernández
- Department of Galenic Pharmacy and Food Technology, Complutense University of Madrid, Madrid, Spain
| | - Lorena Ruiz
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias – Consejo Superior de Investigaciones Científicas, Villaviciosa, Spain
| | - Josué Jara
- Department of Galenic Pharmacy and Food Technology, Complutense University of Madrid, Madrid, Spain
| | - Belén Orgaz
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias – Consejo Superior de Investigaciones Científicas, Villaviciosa, Spain
| | - Juan M. Rodríguez
- Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain
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