You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Myeloid-Derived Suppressor Cells in Umbilical Cord Blood: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Lindsay Dong and Version 1 by Nikoleta Bizymi.

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of myeloid cells that suppress immune responses in cancer, infection, and trauma. They mainly act by inhibiting T-cells, natural-killer cells, and dendritic cells, and also by inducing T-regulatory cells, and modulating macrophages. Although they are mostly associated with adverse prognosis of the underlying disease entity, they may display positive effects in specific situations, such as in allogeneic hematopoietic stem cell transplantation (HSCT), where they attenuate graft-versus-host disease (GVHD). They also contribute to the feto-maternal tolerance, and in the fetus growth process, whereas several pregnancy complications have been associated with their defects. Human umbilical cord blood (UCB) is a source rich in MDSCs.

  • myeloid-derived suppressor cell (MDSC)
  • umbilical cord blood (UCB)
  • feto-maternal immune-tolerance
  • immunology
  • infection
  • autoimmunity
  • inflammation
  • immunotherapy
  • graft-versus-host disease (GVHD)

1. Myeloid-Derived Suppressor Cells

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells with the ability to suppress various types of immune responses [1]. The immunosuppressive properties of myeloid progenitor cell types in the bone marrow (BM) have long been described, since 1987, in a lung cancer model by Young et al. [2]. However, the phenotypic characteristics and biological roles of MDSCs were clarified only recently. This population of cells is mainly characterized by their myeloid origin, their immature state, and their ability to suppress T-cell response [3].
In mice, MDSCs are defined by the expression of the surface markers CD11b and Gr-1 (Ly6G/Ly6C), whereas Gr-1 antigen is not expressed in humans [4]. MDSCs in humans are characterized by the CD11b+CD33+HLA-DR−/low phenotype, and consist of two main subpopulations, namely the granulocytic or polymorphonuclear MDSCs (Gr- or PMN-MDSCs), and the monocytic MDSCs (M-MDSCs); an early MDSC (eMDSC) population is considered the precursor of both subtypes. The PMN-MDSCs appear similar in phenotype to neutrophils, and express the granulocytic markers CD15 and CD66b, the M-MDSCs express the monocytic surface antigen CD14, whereas the eMDSCs express neither CD15 nor CD14 [5]. It should be mentioned that there is not an absolute phenotypic distinction between PMN-MDSCs and neutrophils. However, PMN-MDSCs are low-density cells with characteristic suppressive functions. Recently, the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been reported as a novel marker that further differentiates PMN-MDSCs from other low-density cells [6]. A detailed analysis of the identification of MDSCs in mice and humans is presented in this Special Issue (i.e. Myeloid-Derived Suppressor Cells in Haematology) by Vanhaver et al. [7].
Under normal conditions, the immature myeloid cells generated in the BM are rapidly differentiated into granulocytes, macrophages, or dendritic cells (DCs) [3]. However, under abnormal conditions, the immature myeloid cells expand as a result of a partial blockage of their differentiation. This is the first step required for the generation and accumulation of MDSCs. The essential factors for this step include transforming growth factor beta (TGF-β); interleukin (IL)-1, IL-6, IL-10, IL-12, IL-13; granulocyte macrophage colony stimulating factor (GM-CSF); prostaglandin E2 (PGE2); macrophage colony stimulating factor (M-CSF); cyclooxygenase-2 (COX2); and vascular endothelial growth factor (VEGF) [8,9,10][8][9][10]. The second step requires a proper microenvironment for the activation of MDSCs, and acquisition of their suppressive character through the influence of certain factors, such as interferon-γ (IFN-γ); TGF-β, IL-1β, IL-4, IL-6, IL-10, IL-13; tumor necrosis factor-α (TNF-α); COX-2; hypoxia including factor-1α (HIF-1α); and Toll-like receptor (TLR) ligands [8,11][8][11].
The accumulation of MDSCs was initially described under conditions of malignancy where MDSCs inhibit different cell types, such as T-cells, Natural Killer (NK) cells, DCs, and macrophages [12,13,14][12][13][14]. In different types of tumors, cancer cells produce factors involved in the myelopoiesis (VEGF, GM-CSF, IL-1β, IL-6, HIF-1α, TGF-β, COX-2), as well as in the recruitment (CCL2, CCL3) and activation (TNF-α, IL-10, IL-1β, IL-6, INF-γ, COX-2, HIF-1α) of MDSCs [8,11][8][11]. In addition, MDSCs promote the proliferation and differentiation of Foxp3+ T regulatory cells (Tregs) and tumor-associated macrophages (TAM), which act in favor of tumor progression [15]. Studies in mice demonstrated that MDSCs suppress CD8+ T-cells through cell-to-cell contact, and CD4+ T-cells via non-specific humoral immune mechanisms [16,17][16][17]. The most common of the different suppressive mechanisms of MDSCs is the depletion of essential nutrients (L-arginine, L-cysteine, tryptophan) for T-cell proliferation via the expression of arginase-1 (Arg-1), inducible nitric oxide synthase (iNOS), and indoleamine-2,3-dioxygenase (IDO) [18]. Other mechanisms include the upregulation of COX-2, and the production of peroxynitrite (PNT), which cause nitration of the T-cell receptor-CD8 complex [19,20][19][20]. Except from their immunosuppressive functions, MDSCs play an emerging role in angiogenesis, thus contributing to tumor proliferation and metastasis via the secretion of matrix metalloproteinase (MMP-9), TGF-β, VEGF, and basic fibroblast growth factor (bFGF) [12].
In contrast to previous reports characterizing MDSCs as deleterious cells, there is current evidence suggesting that these cells can display either a positive or negative immune-regulatory role depending on the microenvironment and the situation. Thus, Pastula et al. characterized them as “double-edged sword” [21], whereas Budhwar et al. described them as having both “Yang and Yin” functionality [22]. Surprisingly, even in cancer, MDSCs may have anti-tumor activity through a direct neoplasmatic cells phagocytosing capacity, via interactions with T- and NK cells, and production of cytokines and effector molecules, such as NO, which, in small concentrations, has anti-tumor rather than pro-tumor effects [21].
Accumulation of MDSCs with opposing effects has also been described in conditions other than cancer, namely infections, trauma, obesity, autoimmune diseases, ageing, and transplantation [23]. MDSCs are beneficial during trauma and stress, as they prevent tissue damage through attenuating the excessive activation of the immune system [21]. Probably the most profound example where this function is needed is transplantation, where MDSCs prevent the rejection of the allograft [24]. Elevated levels of MDSCs have been described in the adipose tissue, and may contribute to the increased risk of cancer development in obese individuals; however, their presence may also have a beneficial role by inhibiting the metabolic deregulation observed in obesity [25]. Several studies have indicated that the accumulation of MDSCs in infections from Staphylococcus aureus and Mycobacterium tuberculosis, and in systemic lupus erythematosus, is associated with poor prognosis. In contrast, the abundance of MDSCs has been associated with good prognosis and protection from Pseudomonas aeruginosa and Klebsiella pneumonia infections, and from auto-immune conditions, such as rheumatoid arthritis and immune-related colitis [22,26][22][26]. In accordance with the aforementioned contradictory effects, pregnancy is another condition where MDSCs show not only their “bad”, but also their “good” side.

2. Immune Cells and MDSCs in Pregnancy, Fetal-Maternal Cross-Talk, and Neonatal Period

Pregnancy is a natural situation in which the mother’s immune system develops tolerating mechanisms to prevent rejection of the “allograft” fetal tissue. The maternal immune system provides an immune milieu at the feto-maternal interface, allowing the expression of paternal antigens by the fetus [26,27,28,29][26][27][28][29]. Dynamic changes between trophoblast and decidual immune cells are needed for the successful implantation and the development of the fetus [11]. Several studies demonstrate that, in pregnant women, CD4+ T-cells are biased toward Th2-responses, and CD8+ T-cells are short-lived compared to non-pregnant women [30].
The feto-maternal cross-talk occurs in the placenta, which is composed of both fetal and maternal cells. The Human Leucocyte Antigen (HLA)-G molecule, which is expressed by extravillous trophoblasts (EVTs) of the fetus, plays an important role in implantation and immune tolerance by modulating the immune responses of NK cells, T-cells, DCs, macrophages, innate lymphoid cells, as well as MDSCs [31]. Moreover, sex hormones, and the balance between anti-inflammatory (TGF-β, IL-10) and pro-inflammatory (IL-17) cytokines, also play distinct roles in the maintenance of pregnancy [31,32][31][32]. The cytokine balance is adjusted dynamically during the different phases of pregnancy. More specifically, in the first and third trimester, inflammatory responses are essential for the implantation and the successful fetus delivery, respectively. In contrast, regulatory responses are the major immunological events in the second trimester [33].
The main role of PMN-MDSCs in feto-maternal tolerance is to produce immunosuppressive enzymes (Arg1, IDO, iNOS), and to suppress T-cells through ROS production. PMN-MDSCs from the placenta exhibit increased levels of ROS compared to those from the PB [34]. On the other hand, M-MDSCs, although expressing STAT1, Arg1, and iNOS, show less production of ROS [28]. Several studies in mice have shown that, in the absence of MDSCs, the proliferation of DCs and T-cells is increased, whereas NK cells and macrophages alone are not capable of supporting a successful pregnancy [11].
Besides the suppression of T-cells, MDSCs modulate the polarization of Th-cells. Many studies have shown predominant Th2 and simultaneously suppressed Th1 responses during pregnancy. More specifically, PMN-MDSCs are capable of promoting Th2 responses, and inhibiting Th1 responses in a cell-to-cell-contact-dependent manner [36][35].
One million newborns die each year worldwide due to infections [42,43][36][37]. The vulnerability of neonates and young children to infections is related to the immune system changes during this period of life [44,45,46][38][39][40]. It is thought that alterations in different cell types, such as monocytes, DCs, and NK cells, are responsible for this vulnerability to infections [47][41]. The main characteristics of this period include reduced CD8+ T-cell responses, accumulation of Tregs, and immaturity of DCs [48,49][42][43]. In neonates, CD4+ T-cells are biased towards Th2 responses, and CD8+ T-cells are short-lived [49][43], whereas several studies have shown that increased numbers of MDSCs play a key role as immuno-regulatory cells in fetuses and neonates [50][44]. It has been shown that PMN-MDSCs are increased in the neonates, especially during infection, presenting antimicrobial properties [51][45]. Specifically, neonatal PMN-MDSCs are capable of phagocytosing bacterial pathogens, but also maintain their immunοsuppressive properties [52,53][46][47]. Overall, there is a rather controversial literature on whether MDSCs are protective for fetal infections or not.

3. Immune Cells and MDSCs in the Umbilical Cord Blood (UCB)

The umbilical cord is the link between the fetus and the placenta. It adheres to the fetal part of the placenta; it has a mean length of 60 cm at term; and contains three vessels, i.e., two arteries and one vein, surrounded by the Wharton’s jelly [56][48]. Wharton’s jelly is a tissue composed from connective matrix and mesenchymal stem cells (MSCs) that protects the vessels, and ensures the unhindered transfer of elements from and to the fetus [57][49]. The UCB has gained particular interest as an alternative source of hemopoietic stem cells (HSCs) for transplantation (HSCT) in hematologic diseases. The HSC collection is simple and non-invasive, and the procedure is less frequently associated with graft-versus-host disease (GVHD) compared to BM-based HSCT, and thus, the HLA-matching requirements may be less strict [58][50]. Most of the HSCs present in the fetal circulation, i.e., in the placenta and the umbilical cord, migrate to the BM after delivery; although, some may remain in the above tissues. Interestingly, the concentration of HSCs in the UCB is higher compared to the BM or PB [58][50]. Furthermore, the UCB stem and progenitor cells have longer telomeres and different gene expression profiles, and they can easily expand ex vivo even without growth factors, as they have the ability to produce them in an autocrine manner [60,61][51][52]. Τhe immature CD34+rh123lowCD38− cells, and those expressing Thy-1, present the highest proliferation rates in cultures [60][51]. In contrast, MSCs are present in low numbers in UCB, whereas the identified endothelial cell populations probably derive from the umbilical cord rather than the UCB [58][50]. The numbers of MDSCs in the UCB and the PB of neonates are increased compared to adults, and decrease during the first months of life [50][44]. The number of UCB MDSCs are comparable to those observed in cancer patients [43][37]. It is unclear whether this accumulation of MDSCs in neonates is beneficial or may cause susceptibility to infections. Many studies have demonstrated that the higher amount of MDSCs observed in the umbilical cord of preterm neonates may contribute to the higher risk to infections [51][45]. However, other studies suggest that MDSCs may protect neonates from uncontrolled inflammatory responses, as they produce high levels of anti-microbial agents [52,54][46][53]. The majority of MDSCs in neonates are PMN-MDSCs, and are capable of suppressing the proliferation of T-cells. UCB MDSCs are capable of suppressing Th1 responses, and inducing Th2 responses and Tregs. Th1 responses are mediated through cell-to-cell contact, whereas Th2 responses are mediated through the production of Arg1 and ROS. The induction of Tregs is mediated through iNOS expression [26]. Other studies have shown that UCB PMN-MDSCs have effects on monocytes. More specifically, PMN-MDSCs are responsible of the downregulation of HLA class I and class II molecules; the upregulation of co-inhibitory molecules, such as programmed death ligand-1 (PD-L1) and PD-L2; the decrease of TNF-a and IL-1β; and the increase of IL-8 [63][54]. The interactions and properties of the UCB immune cells are depicted in Figure 1.
Jcm 11 00727 g001 550
Figure 1. Specific characteristics and interactions of different immune cells in the UCB. Immune cells found in the UCB exhibit distinct features, leading to complex immune regulation patterns. Inhibition of immune activation is elicited in multiple manners that implicate MDSCs, among others, finally shifting the balance towards a tolerant microenvironment. Abbreviations: UCB, umbilical cord blood; CD40L, CD40 ligand; DCs, dendritic cells; HLA, human leukocyte antigen; IL, interleukin; MDSCs, myeloid-derived suppressor cells; NK cells, natural-killer cells; PD-L; programmed death ligand; Th: T-helper cells; Tregs, T-regulatory cells; TNF, tumor necrosis factor.

4. Conclusions

MDSC populations, in contrary to what was believed in the past, play an immune-modulatory role that can be either positive or negative depending on the microenvironment and the situation in which these cells grow. They display a beneficial effect during pregnancy, as increased numbers of MDSCs are crucial in the development of immunological tolerance of the fetus. UCB is a source rich in MDSCs, and UCB-MDSCs are gaining particular interest for potential clinical uses, such as, among others, in allogeneic HSCT for GVHD inhibition. As UCB-MDSCs are candidate cells for several promising applications because of their immune-modulatory potential, the UCB units that are not suitable for clinical use in HSCT represent an attractive source for MDSC isolation for research and clinical purposes.

References

  1. Bronte, V.; Brandau, S.; Chen, S.-H.; Colombo, M.P.; Frey, A.B.; Greten, T.F.; Mandruzzato, S.; Murray, P.J.; Ochoa, A.; Ostrand-Rosenberg, S.; et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat. Commun. 2016, 7, 12150.
  2. Young, M.R.; Newby, M.; Wepsic, H.T. Hematopoiesis and suppressor bone marrow cells in mice bearing large metastatic Lewis lung carcinoma tumors. Cancer Res. 1987, 47, 100–105.
  3. Gabrilovich, D.I.; Nagaraj, S. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 2009, 9, 162–174.
  4. Arocena, A.R.; Onofrio, L.I.; Pellegrini, A.V.; Silva, E.A.C.; Paroli, A.; Cano, R.C.; Aoki, M.P.; Gea, S. Myeloid-derived suppressor cells are key players in the resolution of inflammation during a model of acute infection. Eur. J. Immunol. 2013, 44, 184–194.
  5. Gabrilovich, D.I. MDSCs. Cancer Immunol. Res. 2018, 5, 3–8.
  6. Seman, B.G.; Robinson, C.M. The Enigma of Low-Density Granulocytes in Humans: Complexities in the Characterization and Function of LDGs during Disease. Pathogens 2021, 10, 1091.
  7. Vanhaver, C.; van der Bruggen, P.; Bruger, A. MDSC in Mice and Men: Mechanisms of Immunosuppression in Cancer. J. Clin. Med. 2021, 10, 2872.
  8. Millrud, C.R.; Bergenfelz, C.; Leandersson, K. On the origin of myeloid-derived suppressor cells. Oncotarget 2016, 8, 3649–3665.
  9. Bunt, S.K.; Yang, L.; Sinha, P.; Clements, V.K.; Leips, J.; Ostrand-Rosenberg, S. Reduced Inflammation in the Tumor Microenvironment Delays the Accumulation of Myeloid-Derived Suppressor Cells and Limits Tumor Progression. Cancer Res. 2007, 67, 10019–10026.
  10. Gabitass, R.F.; Annels, N.E.; Stocken, D.D.; Pandha, H.A.; Middleton, G.W. Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol. Immunother. 2011, 60, 1419–1430.
  11. Ahmadi, M.; Mohammadi, M.; Ali-Hassanzadeh, M.; Zare, M.; Gharesi-Fard, B. MDSCs in pregnancy: Critical players for a balanced immune system at the feto-maternal interface. Cell. Immunol. 2019, 346, 103990.
  12. Umansky, V.; Blattner, C.; Gebhardt, C.; Utikal, J. The Role of Myeloid-Derived Suppressor Cells (MDSC) in Cancer Progression. Vaccines 2016, 4, 36.
  13. Mauti, L.A.; Le Bitoux, M.-A.; Baumer, K.; Stehle, J.-C.; Golshayan, D.; Provero, P.; Stamenkovic, I. Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation. J. Clin. Investig. 2011, 121, 2794–2807.
  14. Poschke, I.; Mao, Y.; Adamson, L.; Salazar-Onfray, F.; Masucci, G.; Kiessling, R. Myeloid-derived suppressor cells impair the quality of dendritic cell vaccines. Cancer Immunol. Immunother. 2011, 61, 827–838.
  15. Fleming, V.; Hu, X.; Weber, R.; Nagibin, V.; Groth, C.; Altevogt, P.; Utikal, J.; Umansky, V. Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression. Front. Immunol. 2018, 9, 398.
  16. Tebartz, C.; Horst, S.A.; Sparwasser, T.; Huehn, J.; Beineke, A.; Peters, G.; Medina, E. A Major Role for Myeloid-Derived Suppressor Cells and a Minor Role for Regulatory T Cells in Immunosuppression during Staphylococcus aureus Infection Christina. J. Immunol. 2015, 194, 1100–1111.
  17. Tsukamoto, H.; Nishikata, R.; Senju, S.; Nishimura, Y. Myeloid-Derived Suppressor Cells Attenuate T H 1 Development through IL-6 Production to Promote Tumor Progression. Cancer Immunol. Res. 2013, 1, 64–76.
  18. Condamine, T.; Gabrilovich, D.I. Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function. Trends Immunol. 2011, 32, 19–25.
  19. De Sanctis, F.; Solito, S.; Ugel, S.; Molon, B.; Bronte, V.; Marigo, I. MDSCs in cancer: Conceiving new prognostic and therapeutic targets. Biochim. Biophys. Acta 2016, 1865, 35–48.
  20. Solito, S.; Pinton, L.; Mandruzzato, S. In Brief: Myeloid-derived suppressor cells in cancer. J. Pathol. 2017, 242, 7–9.
  21. Pastuła, A.; Marcinkiewicz, J. Myeloid-derived suppressor cells: A double-edged sword? Int. J. Exp. Pathol. 2011, 92, 73–78.
  22. Budhwar, S.; Verma, P.; Verma, R.; Rai, S.; Singh, K. The Yin and Yang of Myeloid Derived Suppressor Cells. Front. Immunol. 2018, 9, 2776.
  23. Pawelec, G.; Verschoor, C.P.; Ostrand-Rosenberg, S. Myeloid-Derived Suppressor Cells: Not Only in Tumor Immunity. Front. Immunol. 2019, 10, 1099.
  24. Zhang, C.; Wang, S.; Yang, C.; Rong, R. The Crosstalk between Myeloid Derived Suppressor Cells and Immune Cells: To Establish Immune Tolerance in Transplantation. J. Immunol. Res. 2016, 2016, 4986797.
  25. Ostrand-Rosenberg, S. Myeloid derived-suppressor cells: Their role in cancer and obesity. Curr. Opin. Immunol. 2018, 51, 68–75.
  26. Köstlin-Gille, N.; Gille, C. Myeloid-Derived Suppressor Cells in Pregnancy and the Neonatal Period. Front. Immunol. 2020, 11, 584712.
  27. Wegmann, T.G.; Lin, H.; Guilbert, L.; Mosmann, T.R. Biderectional cytokine interactions in the maternal-fetal relationship: Is successful pregnancy a TH2 phenomenon ? Immunol Today. 1993, 14, 5–8.
  28. Zhao, A.; Xu, H.; Kang, X.; Zhao, A.; Lu, L. New insights into myeloid-derived suppressor cells and their roles in feto-maternal immune cross-talk. J. Reprod. Immunol. 2016, 113, 35–41.
  29. Crncic, T.B.; Laskarin, G.; Juretic, K.; Strbo, N.; Dupor, J.; Srsen, S.; Randic, L.; Bouteiller, P.L.; Tabiasco, J.; Rukavina, D. Perforin and Fas/FasL Cytolytic Pathways at the Maternal—Fetal Interface. Am. J. Reprod. Immunol. 2005, 54, 241–248.
  30. Raghupathy, R. Th 1-type immunity is incompatible with successful pregnancy. Immunol. Today 1997, 18, 478–482.
  31. Tripathi, S.; Guleria, I. Biomarkers in Fetomaternal Tolerance. Clin. Lab. Med. 2018, 39, 145–156.
  32. Robinson, D.P.; Klein, S.L. Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis. Horm. Behav. 2012, 62, 263–271.
  33. Mor, G.; Cardenas, I.; Abrahams, V.; Guller, S. Inflammation and pregnancy: The role of the immune system at the implantation site. Ann. N. Y. Acad. Sci. 2011, 1221, 80–87.
  34. Köstlin, N.; Kugel, H.; Spring, B.; Leiber, A.; Marmé, A.; Henes, M.; Rieber, N.; Hartl, D.; Poets, C.F.; Gille, C. Granulocytic myeloid derived suppressor cells expand in human pregnancy and modulate T-cell responses. Eur. J. Immunol. 2014, 44, 2582–2591.
  35. Sykes, L.; MacIntyre, D.A.; Yap, X.J.; Teoh, T.G.; Bennett, P.R. The Th1:Th2 Dichotomy of Pregnancy and Preterm Labour. Mediat. Inflamm. 2012, 2012, 967629.
  36. Blencowe, H.; Cousens, S. Review: Addressing the challenge of neonatal mortality. Trop. Med. Int. Health 2013, 18, 303–312.
  37. Gantt, S.; Gervassi, A.; Jaspan, H.; Horton, H. The Role of Myeloid-Derived Suppressor Cells in Immune Ontogeny. Front. Immunol. 2014, 5, 387.
  38. Levy, O. Innate immunity of the newborn: Basic mechanisms and clinical correlates. Nat. Rev. Immunol. 2007, 7, 379–390.
  39. Philbin, V.J.; Levy, O. Developmental Biology of the Innate Immune Response: Implications for Neonatal and Infant Vaccine Development. Pediatr. Res. 2009, 65, 98R–105R.
  40. Wilson, C.B.; Lewis, D.B. Basis and Implications of Selectively Diminished Cytokine Production in Neonatal Susceptibility to Infection. Clin. Infect. Dis. 1990, 12, S410–S420.
  41. Kollman, T.R.; Levy, O.; Montgomery, R.R.; Goriely, S. Innate Immune Sensing by Toll-like Receptors in Newborns and the Elderly. Immunity 2012, 37, 771–783.
  42. Maródi, L. Innate cellular immune responses in newborns. Clin. Immunol. 2006, 118, 137–144.
  43. Zaghouani, H.; Hoeman, C.M.; Adkins, B. Neonatal immunity: Faulty T-helpers and the shortcomings of dendritic cells. Trends Immunol. 2009, 30, 585–591.
  44. Rieber, N.; Gille, C.; Köstlin, N.; Schäfer, I.; Spring, B.; Ost, M.; Spieles, H.; Kugel, H.A.; Pfeiffer, M.; Heininger, V.; et al. Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses. Clin. Exp. Immunol. 2013, 174, 45–52.
  45. Schwarz, J.; Scheckenbach, V.; Kugel, H.; Spring, B.; Pagel, J.; Härtel, C.; Pauluschke-Fröhlich, J.; Peter, A.; Poets, C.F.; Gille, C.; et al. Granulocytic myeloid-derived suppressor cells (GR-MDSC) accumulate in cord blood of preterm infants and remain elevated during the neonatal period. Clin. Exp. Immunol. 2017, 191, 328–337.
  46. Leiber, A.; Schwarz, J.; Köstlin, N.; Spring, B.; Fehrenbacher, B.; Katava, N.; Poets, C.F.; Gille, C. Neonatal myeloid derived suppressor cells show reduced apoptosis and immunosuppressive activity upon infection with Escherichia coli. Eur. J. Immunol. 2017, 47, 1009–1021.
  47. Gervassi, A.; Lejarcegui, N.; Dross, S.; Jacobson, A.; Itaya, G.; Kidzeru, E.; Gantt, S.; Jaspan, H.; Horton, H. Myeloid Derived Suppressor Cells Are Present at High Frequency in Neonates and Suppress In Vitro T Cell Responses. PLoS ONE 2014, 9, e107816.
  48. Muniraman, H.; Sardesai, T.; Sardesai, S. Disorders of the Umbilical Cord. Pediatr. Rev. 2018, 39, 332–341.
  49. Taghizadeh, R.; Cetrulo, K.; Cetrulo, C. Wharton’s Jelly stem cells: Future clinical applications. Placenta 2011, 32, S311–S315.
  50. Rogers, I.; Casper, R.F. Umbilical cord blood stem cells. Best Pract. Res. Clin. Obstet. Gynaecol. 2004, 18, 893–908.
  51. Gluckman, E. Umbilical cord blood biology and transplantation. Curr. Opin. Hematol. 1995, 2, 413–416.
  52. Mayani, H. Umbilical Cord Blood: Lessons Learned and Lingering Challenges after More Than 20 Years of Basic and Clinical Research. Arch. Med Res. 2011, 42, 645–651.
  53. He, Y.-M.; Li, X.; Perego, M.; Nefedova, Y.; Kossenkov, A.V.; A Jensen, E.; Kagan, V.E.; Liu, Y.-F.; Fu, S.-Y.; Ye, Q.-J.; et al. Transitory presence of myeloid-derived suppressor cells in neonates is critical for control of inflammation. Nat. Med. 2018, 24, 224–231.
  54. Dietz, S.; Schwarz, J.; Vogelmann, M.; Spring, B.; Molnár, K.; Orlikowsky, T.W.; Wiese, F.; Holzer, U.; Poets, C.F.; Gille, C.; et al. Cord blood granulocytic myeloid-derived suppressor cells impair monocyte T cell stimulatory capacity and response to bacterial stimulation. Pediatr. Res. 2019, 86, 608–615.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Academic Video Service
Feedback