Human umbilical cord blood-derived mast cells

Abstract

Findings obtained using animal models have often failed to reflect the processes involved in human disease. Moreover, human cultured cells do not necessarily function as their actual tissue counterparts. Therefore, there is great demand for sources of human progenitor cells that may be directed to acquire specific tissue characteristics and be available in sufficient quantities to carry out functional and pharmacological studies. Acase in point is the mast cell, well known for its involvement in allergic reactions, but also implicated in inflammatory diseases. Mast cells can be activated by allergens, anaphylatoxins, immunoglobulin-free light chains, superantigens, neuropeptides, and cytokines, leading to selective release of mediators. These could be involved in many inflammatory diseases, such as asthma and atopic dermatitis, which worsen by stress, through activation by local release of corticotropin-releasing hormone or related peptides. Umbilical cord blood and cord matrix-derived mast cell progenitors can be separated magnetically and grown in the presence of stem cell factor, interleukin-6, interleukin-4, and other cytokines to yield distinct mast cell populations. The recent use of live cell array, with its ability to study such interactions rapidly at the single-cell level, provides unique new opportunities for fast output screening of mast cell triggers and inhibitors.

Generation of Mast Cells from Mouse Fetus: Analysis of Differentiation and Functionality, and Transcriptome Profiling Using Next Generation Sequencer

“…For instance, P38MAPKα knockout mice are known to be embryonic lethal and die in mid-gestation with defects in placental and embryonic vasculature [16]. In such cases of fetal death by gene manipulation, the functional analysis of proteins in mast cells is virtually impossible because both “isolated” and “generated” mast cells are derived from adult tissues; specifically, they are isolated from lung [17], skin [18], [19], tonsil [19] and peritoneal fluid [20], and are generated from bone marrow [21], peripheral blood [22] and umbilical cord blood [23]. In the present study, we generated mast cells from mouse fetal liver cells (FLMC) and compared the properties with bone marrow-derived mast cells (BMMC).…”

Psychoneuroimmunology of Psychological Stress and Atopic Dermatitis: Pathophysiologic and Therapeutic Updates

“…The use of live cell array to rapidly uncover mast cell biology at the cellular level provides a unique opportunity for further study of mast cell triggers and inhibitors, and their contribution to stress-induced exacerbation of AD (147). …”

Mast Cells Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-inflammatory Cytokines IL-37, IL-38 and IL-1Ra

“…IL-33 is localized in the cell nucleus and by binding to p65 of NF-kB it can also have an inhibitory action on the transcription activity of NF-kB, in fact, IL-33 in regulating Th2 cells has a contrast to pro-inflammatory IL-18 [53]. In psoriasis can be an augmentation of neurotransmitters such as substance P (SP) which induces VEGF in human mast cells, an effect that leads to increased IL-33 and inflammation [1]. IL-33 which is released from MCs without cleavage by caspase 1, is a critical player of immune response to tissue suffering and acts through its ST2 receptor, a member of the IL-1 family, located in the human chromosome 2 locus, implicated in T helper 2 (Th2) responses in MCs-driven allergic diseases.…”

“…The disease is associated with a high degree of morbidity, and the patients affected have a decreased quality of life. Psoriasis is a common disease that presents skin lesions, dysregulated immune system and chronic inflammation, problems that are still unresolved [1], although in recent years, biomedical research has made substantial advances in elucidating the pathogenic mechanisms. Predisposition to psoriasis may be due to environmental factors such as stress, drugs, microorganisms, smoking, and trauma, but also to the dysregulation of the immune system and, in particular, to the imbalance of some immune regulatory cytokines [2].…”