© Borgis - Postępy Nauk Medycznych 9/2017, s. 460-463
*Małgorzata Witkowska-Zimny1, Ewa Kamińska-El-Hassan1, Joanna Wójtowicz2
Human breastmilk as a source of progenitor/stem cells
Mleko kobiece jako źródło komórek progenitorowych/macierzystych
1Department of Biophysics and Human Physiology, Medical University of Warsaw
Head of Department: Professor Jacek Przybylski, MD, PhD
2Department of Paediatrics, Centre of Postgraduate Medical Education, Warsaw
Head of Department: Associate Professor Teresa Jackowska, MD, PhD
Streszczenie
Wstęp. Właściwości odżywcze mleka kobiecego są znane od dawna, ale obecnie pokarm kobiecy jest traktowany jako element terapii. Badania wskazują na obecność w nim komórek progenitorowych/macierzystych.
Cel pracy. Celem pracy było potwierdzenie obecności komórek macierzystych w mleku kobiecym oraz weryfikacja ich pluripotencjalności.
Materiał i metody. Próbki mleka (20-30 ml) uzyskane były od zdrowych kobiet w 3. dobie po naturalnym porodzie. Izolacja komórek progenitorowych i macierzystych została przeprowadzona z zastosowaniem metody opisanej przez Hassiotou i wsp. z modyfikacjami. Wyizolowane komórki były hodowane w warunkach in vitro i charakteryzowane na poziomie molekularnym.
Wyniki. W hodowli in vitro otrzymano kilka typów komórek. Komórki macierzyste zidentyfikowane w mleku wykazywały ekspresję genów pluripotencjalności: OCT4, SOX2, NANOG, w odróżnieniu od komórek kontrolnych.
Wnioski. Mleko kobiece zawiera heterogenną populację komórek. Może być ono łatwodostępnym, nieinwazyjnym źródłem komórek progenitorowych i macierzystych o wzmożonej ekspresji genów pluripotencji.
Summary
Introduction. Human breastmilk is a complex fluid adapted to satisfy the nutritional requirements of an infant. Some studies indicate the presence of progenitor/stem cells in the human breastmilk.
Aim. The aim of this study was to obtain in vitro culture of the breast milk-derived cells and identify expression of pluripotency genes in the cells.
Material and methods. Mature breastmilk (20-30 ml) samples were obtained from health breastfeeding women in very early range of lactation in a aseptic way. The isolation procedure was based on the protocols described by Hassiotou et al. with modifications. The cells were cultured in vitro under standard conditions and characterized on molecular level.
Results. The presence of the cells of various origin was detected in human breastmilk. The isolated breast-milk-derived cells were adherent to the plates. We found the expression of pluripotency genes: OCT4, SOX2 and NANOG in the isolated breastmilk cells by real-time PCR and present it in contrary to human bone-marrow derived stem cells.
Conclusions. Human breastmilk contains a variety of cells. A population of progenitor/stem cells express pluripotency genes. Human breastmilk could be therefore a non-invasive source of progenitor cells for regenerative and personal medicine in the future.
Introduction
Stem cell biology has become an intriguing field. Several types of human stem cells have been isolated and identified in vivo and in vitro. The presence of stem/progenitor cells, called human breastmilk-derived stem cells (hBSCs) has been found in mother’s milk in recent years (1, 2). The cell population in the breastmilk derives from various sites of the mammary gland. Blood-derived leukocytes are the best-known, luminal epithelial cells and myoepithelial cells residing in the breast are described (3), whereas the hBSCs are the most extensively studied recently. New data revealed that leukocytes constitute only a small minority (< 2%) of the cells in a mature milk of healthy mother (4). Luminal and myoepithelial cells and their precursors represent nearly 80-98% of the non-immune cell types found in human milk in healthy condition (5). Numbers of breastmilk stem cells with multilineage properties is estimated at 5-10% of cell population in colostrum (2, 6). According to the recent evidence, breastmilk stem/progenitor cells are scarce in the resting breast; however, they are activated during pregnancy and lactation, undergoing a controlled program of proliferation, differentiation and apoptosis stimulated by hormonally-driven cues. However, breastmilk cell complexity is very individual and it subject to various factors such as the stage of lactation, the degree of breast fullness, infant feeding, the health status of the breastfeeding dyad, and others.
Term “stem cells” may refer to various types of cells which (a) are unspecialized and can generate one or more cell lineage types of the three germ layers, (b) have the ability to replenish their own population (feature of self-renewal). Expression of the three transcription factors, OCT4, SOX2 and NANOG, is essential for the major properties of stem cells: self-renewal and pluripotency (7). In this study we evaluated the expression of these genes in the breastmilk-derived cells. OCT-4 (octamer-binding transcription factor 4) is a pluripotency regulator that controls lineage commitment of embryonic stem cells (8). SOX 2 is a member of the SRY-related HMG-box (SOX) transcription factor family with a diverse role in stem cell potency and maintenance, embryonic development and cancer (9). OCT4 together with SOX2 stimulate the expression of NANOG (10). The presence of pluripotent stem cells in human milk generates numerous questions and implications for breastfeeding, newborn and maternal health, but also opens a new perspective of future potential applications of these cells in the personal and regenerative medicine.
Aim
The objectives of the current study were to identify the cellular constituents of human breastmilk by phenotypic characterization of the cells and expression of the pluripotent markers.
Material and methods
Collection of breastmilk samples
All procedures were approved by the 2nd Local Ethical Committee at the Medical University of Warsaw (Decision No. KB/239/2016). The breastmilk samples were obtained between 1st and 4th day post-delivery from two healthy volunteers in the morning. Breastmilk (20-30 ml) samples were transported to the laboratory immediately under aseptic condition.
Breastmilk cell isolation and culture
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Piśmiennictwo
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