Functionality of bone marrow mesenchymal stromal cells derived from head and neck cancer patients - A FDA-IND enabling study regarding MSC-based treatments for radiation-induced xerostomia.

Purpose: Salivary dysfunction is a significant side effect of radiation therapy for head and neck cancer (HNC). Preliminary data suggests that mesenchymal stromal cells (MSCs) can improve salivary function. Whether MSCs from HNC patients who have completed chemoradiation are functionally similar to those from healthy patients is unknown.

Endometrial and placental stem cells in successful and pathological pregnancies.

The endometrium is a dynamic tissue that undergoes extensive remodeling during the menstrual cycle and further gets modified during pregnancy. Different kinds of stem cells are reported in the endometrium. These include epithelial stem cells, endometrial mesenchymal stem cells, side population stem cells, and very small embryonic-like stem cells.

A STAT5-Smad3 dyad regulates adipogenic plasticity of visceral adipose mesenchymal stromal cells during chronic inflammation.

Adipogenic differentiation of visceral adipose tissue-resident multipotent mesenchymal stromal cells (VA-MSC) into adipocytes is metabolically protective. Under chronic inflammatory stress, this neoadipogenesis process is suppressed by various pro-inflammatory cytokines and growth factors. However, the underlying mechanism(s) regulating VA-MSC plasticity remains largely unexplored.

Translationally Controlled Tumor Protein-Mediated Stabilization of Host Antiapoptotic Protein MCL-1 Is Critical for Establishment of Infection by Intramacrophage Parasite .

In the early phase of infection, the intramacrophage pathogen protects its niche with the help of the antiapoptotic protein myeloid cell leukemia-1 (MCL-1). Whether could exploit MCL-1, an extremely labile protein, at the late phase is still unclear. A steady translational level of MCL-1 observed up to 48 h postinfection and increased caspase-3 activity in MCL-1-silenced infected macrophages documented its importance in the late hours of infection.

Emerging roles of bromodomain protein 4 in regulation of stem cell identity.

Understanding the mechanism of fate decision and lineage commitment is the key step for developing novel stem cell applications in therapeutics. This process is coordinately regulated through systematic epigenetic reprogramming and concomitant changes in the transcriptional landscape of the stem cells. One of the bromo- and extra-terminal domain (BET) family member proteins, bromodomain protein 4 (BRD4), performs the role of epigenetic reader and modulates gene expression by recruiting other transcription factors and directly regulating RNA polymerase II elongation.

Minor salivary gland mesenchymal stromal cells derived from patients with Sjӧgren's syndrome deploy intact immune plasticity.

Background Aims: Mesenchymal stromal cells (MSCs) provide minor salivary glands (MSGs) with support and niche cells for epithelial glandular tissue. Little is known about resident MSG-derived MSCs (MSG-MSCs) in primary Sjӧgren's syndrome (PSS). The authors' objective is to define the immunobiology of endogenous PSS MSG-MSCs.

Mesenchymal stromal cell therapeutic potency is dependent upon viability, route of delivery, and immune match.

Culture-adapted bone marrow mesenchymal stromal cells (MSCs) deploy paracrine anti-inflammatory and tissue regenerative functionalities that can be harnessed as a living cell pharmaceutical product. Independent of clinical indication, a near majority of human clinical trials administer MSC IV, often with an allogeneic MSC cell product immediately after thawing from cryostorage. Despite hundreds of studies in a wide assortment of inflammatory, degenerative, and acute tissue injury syndromes, human clinical outcomes often fail to mirror promising rigorously conducted preclinical animal studies.

CCL2 and CXCL12 Derived from Mesenchymal Stromal Cells Cooperatively Polarize IL-10+ Tissue Macrophages to Mitigate Gut Injury.

Mesenchymal stromal cell (MSC)-based therapy for inflammatory diseases involves paracrine and efferocytotic activation of immunosuppressive interleukin-10 (IL-10) macrophages. The paracrine pathway for MSC-mediated IL-10 macrophage functionality and response to tissue injury is not fully understood. In our present study, clodronate pre-treatment of colitic mice confirms the essential role of endogenous macrophages in bone-marrow-derived MSC (BM-MSC)-mediated clinical rescue of dextran sulfate sodium (DSS)-induced colitis.

Leishmania donovani Exploits Myeloid Cell Leukemia 1 (MCL-1) Protein to Prevent Mitochondria-dependent Host Cell Apoptosis.

Apoptosis is one of the mechanisms used by host cells to remove unwanted intracellular organisms, and often found to be subverted by pathogens through use of host anti-apoptotic proteins. In the present study, with the help of in vitro and in vivo approaches, we documented that the macrophage anti-apoptotic protein myeloid cell leukemia 1 (MCL-1) is exploited by the intra-macrophage parasite Leishmania donovani to protect their "home" from actinomycin D-induced mitochondria-dependent apoptosis. Among all the anti-apoptotic BCL-2 family members, infection preferentially up-regulated expression of MCL-1 at both the mRNA and protein levels and compared with infected control, MCL-1-silenced infected macrophages documented enhanced caspase activity and increased apoptosis when subjected to actinomycin D treatment.

Leishmania donovani targets tumor necrosis factor receptor-associated factor (TRAF) 3 for impairing TLR4-mediated host response.

Intramacrophage pathogen Leishmania donovani escapes host immune response by subverting Toll-like receptor (TLR) signaling, which is critically regulated by protein ubiquitination. In the present study, we identified tumor necrosis factor receptor-associated factor (TRAF) 3, degradative ubiquitination of which is essential for TLR4 activation, as a target for Leishmania to deactivate LPS-mediated TLR4 signaling. We used LPS-treated RAW 264.

Leishmania donovani prevents oxidative burst-mediated apoptosis of host macrophages through selective induction of suppressors of cytokine signaling (SOCS) proteins.

One of the mechanisms for establishment of infection employed by intra-macrophage pathogen-like Leishmania is inhibition of oxidative burst-mediated macrophage apoptosis to protect their niche for survival and replication. We tried to elucidate the underlying mechanism for this by using H2O2 for induction of apoptosis. Leishmania donovani-infected macrophages were much more resistant to H2O2-mediated apoptosis compared with control.