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Background: Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite remarkable short-term recovery, long-term lung survival continues to face several major challenges, including chronic rejection and severe toxic side effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The novel Cymerus™ manufacturing facilitates production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection., Methods: Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c → C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium, and collagen deposition during rejection., Results: We demonstrated that iPSC-derived MSC treatment leads to significant increases in hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, and IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post transplantation., Conclusions: Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune tolerance and rescue allograft from sustained hypoxic/ischemic phase, and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.

Background: Human decidua basalis mesenchymal stem/multipotent stromal cells (DBMSCs) inhibit endothelial cell activation by inflammation induced by monocytes. This property makes them a promising candidate for cell-based therapy to treat inflammatory diseases, such as atherosclerosis. This study was performed to examine the ability of DBMSCs to protect endothelial cell functions from the damaging effects resulting from exposure to oxidatively stress environment induced by H 2 O 2 and monocytes., Methods: DBMSCs were co-cultured with endothelial cells isolated from human umbilical cord veins in the presence of H 2 O 2 and monocytes, and various functions of endothelial cell were then determined. The effect of DBMSCs on monocyte adhesion to endothelial cells in the presence of H 2 O 2 was also examined. In addition, the effect of DBMSCs on HUVEC gene expression under the influence of H 2 O 2 was also determined., Results: DBMSCs reversed the effect of H 2 O 2 on endothelial cell functions. In addition, DBMSCs reduced monocyte adhesion to endothelial cells and also reduced the stimulatory effect of monocytes on endothelial cell proliferation in the presence of H 2 O 2 . Moreover, DBMSCs modified the expression of many genes mediating important endothelial cell functions. Finally, DBMSCs increased the activities of glutathione and thioredoxin reductases in H 2 O 2 -treated endothelial cells., Conclusions: We conclude that DBMSCs have potential for therapeutic application in inflammatory diseases, such as atherosclerosis by protecting endothelial cells from oxidative stress damage. However, more studies are needed to elucidate this further.

Background: Human decidua parietalis mesenchymal stem/multipotent stromal cells (DPMSCs) have unique phenotypic and functional properties that make them promising candidates for cell-based therapy. Here, we investigated DPMSC interaction with natural killer (NK) cells, and the effects of this interaction on NK cell phenotypic characteristics and functional activities., Methods: DPMSCs isolated from the decidua parietalis of human fetal membranes were cultured with interleukin (IL)-2-activated and IL-2-unactivated NK cells isolated from healthy human peripheral blood. NK cell proliferation and cytolytic activities were then examined using functional assays. NK cell expression of receptors mediating the cytolytic activity against DPMSCs, and the mechanism underlying this effect on DPMSCs, were also examined using flow cytometry and light microscopy, respectively., Results: DPMSCs stimulated IL-2-induced proliferation of resting NK cells and the proliferation of activated NK cells. Moreover, IL-2-activated NK cells, but not freshly isolated NK cells, efficiently lysed DPMSCs. The induction of this NK cell cytolytic activity against DPMSCs was mediated by the activating NK cell receptors NKG2D, CD69, NKp30, and NKp44. However, DPMSCs showed a direct induction of NK cell cytolytic activity through CD69. We also found that DPMSCs expressed the ligands for these activating NK cell receptors including Nectin-2, ULBP-2, MICA, and MICB. Although DPMSCs expressed HLA class I molecules, they were susceptible to lysis by NK cells, suggesting that HLA class I antigens do not play a significant role in NK cell cytolytic action. In addition, DPMSCs did not inhibit NK cell cytolytic activity against cancer cells. Importantly, DPMSCs significantly increased NK expression of inflammatory molecules with anticancer activities., Conclusions: We conclude that DPMSCs have potential for therapeutic application in cancer therapy, but not in transplantation or immunological diseases.

Background: Rhazya stricta Decne. is a medicinal plant that is widespread in Saudi Arabia and desert areas of the Arabian Peninsula. Its extract contains alkaloids, tannins, and flavonoids that are involved in different biological activities. The study aim was to evaluate the effects of Rhazya stricta plant extracts on the proliferation and differentiation of NTERA-2 (NT2) pluripotent embryonal carcinoma cells., Methods: Soxhlet extraction was carried out using different solvents to extract stems, leaves and fruit parts of this plant. Cytotoxicity was evaluated by an MTS cell viability assay. The ability of the plant extract to induce cell differentiation was examined phenotypically using an inverted light microscope. The expression of pluripotency markers was investigated by reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry. Phytochemical screening of chloroform stem extracts was carried out and a chromatographic fingerprint was generated using gas chromatography - mass spectrometry (GC-MS)., Results: Chloroform stem extract induced differentiation of NT2 cells at 5 μg/ml, and the differentiated cells exhibited neurite formation. Following induction of differentiation, there was significant down-regulation of the pluripotency marker genes Oct4 and Sox2. In addition, the surface antigen pluripotency marker, TRA-1-60, was strongly down-regulated. Phytochemical analysis of the extract showed the presence of alkaloids and saponins. The chromatogram revealed the presence of fifteen compounds with different retention times., Conclusion: Our results demonstrate for the first time that chloroform stem extract of R. stricta can induce neuronal differentiation of stem cells at an early stage and may contain potential therapeutic agent that can be used in neurodegenerative diseases.

Background: Few studies investigated the association between basal metabolic rate (BMR) and indicators of pulmonary function. This study was conducted to estimate BMR in overweight/obese and non-obese healthy subjects using four commonly used predictive equations and to investigate its relation to the indicators of lung function tests (LFT). A cross sectional study was conducted in Tabuk University, Tabuk, Saudi Arabia. A total of 201 students (98 males and 103 females) participated in the study. Four different values of BMR were calculated for each participant using four different predictive equations (Harris-Benedict, Mifflin, FAO/WHO/UNU and Henry-Rees). A portable All-flow spirometer (Clement Clarke International, Harlow, UK) was used for measurements of LFT., Results: Significantly higher values of spirometric indicators (p < 0.05) were found in males compared to females, except for FEF75 and FEF75-85. Mean BMR values predicted with the four equations were significantly higher in the males compared to the females and among the overweight/obese compared to the non-obese subjects (p < 0.05). The relation between mean BMR values and the indicators of LFT was statistically insignificant (p > 0.05)., Conclusion: Mean values of LFT indicators are not related to the estimated values of BMR. A practical calculation of BMR based on direct measurement of oxygen consumption is recommended to confirm the absence of this association.

Background: Both obesity and type II diabetes mellitus are associated with insulin resistance and abnormal metabolic reactions. This study was conducted to evaluate resting metabolic rate in obese diabetic patients and to assess its relation to glycaemic control., Results: This is a case control study conducted in Gabir AbuEliz centre in Khartoum, Sudan. A random sample of 40 obese diabetic patients (cases) and 40 obese non-diabetic subjects (controls) were interviewed and examined clinically to exclude presence of acute or chronic medical illness. Haemoglobin A1c was measured for each participant using the "NycoCard Haemoglobin A1c test" (Axis -Shield/ Norway). Fasting blood sugar was measured using one touch(R) glucometer (LifeScan Canada Ltd). The PowerLab 8/35 with a gas analyzer (AD Instruments, Castle Hill Australia) was used for measurement of VO2, VCO2 and Respiratory exchange ratio (RER). Resting metabolic rate was calculated using the Weir equation. VO2 (mean+/-SD) ml/min was significantly higher among cases (209.9+/-42.7) compared to the controls (192.4+/-28.1), (P = 0.034). Similarly, VCO2 (mean+/-SD) ml/min was higher among cases (191.4+/-35.0) than controls (178.3+/-22.5), (P = 0.05). Resting metabolic rate "RMR" (mean+/-SD) kcal/day was higher in obese diabetic patients (1480.7 +/- 274.2) than obese non-diabetic subjects (1362.4+/- 184.8), (P = 0.027). Participants with high glycated haemoglobin had higher RMR than those with normal glycated haemoglobin (P = 0.016)., Conclusion: It is concluded that resting metabolic rate is significantly higher in obese diabetic patients compared to obese non-diabetics, especially in those with poor glycaemic control.