bax inhibitor It should be noted that the apparently inconsi
It should be noted that the apparently inconsistent results regarding the CD146 status of human ASCs, which were obtained in several studies (Bourin et al., 2013) could at least in part be explained with transitory cells of different sizes, which contain different CD146 protein levels, and with maturating ASCs of different sizes, which also contain different CD146 protein levels. Moreover, the present study indicates that BMSCs and ASCs have a different cell surface phenotype. Based on transplantation assays in Sacchetti et al., 2016, they are also not the same with respect to differentiation capacity.
We demonstrated in the present study that the CD146 gene is expressed at low levels in ASCs relative to other SVF cells, such as endothelial cells and pericytes. Similar to human endothelial cells, human ASCs contain two different splicing variants of the CD146 mRNA: CD146-long, and CD146-short. CD146-long mRNA is more abundant. The vast majority of the CD146 protein in ASCs is CD146-long, which is not tethered to the cell surface. The CD146 protein is highly stable and predominantly localized in the Golgi apparatus. While CD146 long has been found in all species analyzed to date (Wang and Yan, 2013), CD146-short protein has only been detected in mice (Kohama et al., 2005), dogs (Guezguez et al., 2007) and bax inhibitor (Taira et al., 1995). We show for the first time that human ASCs also contain low levels of CD146-short protein. The long and short isoforms of CD146 have the same extracellular and transmembrane domains, but differ by their cytoplasmic tails (Wang and Yan, 2013).
The role of CD146 in the different cell types of the adipose niche is not precisely understood. As a cell adhesion molecule involved in cell–cell interactions (Wang and Yan, 2013), CD146 plays a role in endothelial cell-cell interactions in small vessels and for adhesion of pericytes to the vascular wall. Our findings suggest that cell surface-tethered CD146 could also play a role in the migration and spatial orientation of transitory cells in the adipose niche. It is tempting to speculate on the function of intracellular CD146 in ASCs. However, more work is necessary to better understand the biochemical and physiological roles of CD146 in these cells.
The following are the supplementary data related to this article.
Materials and methods
Conclusion The current study avers the cytoprotective role of DADLE-induced DOR activation on hUCB-BFs under ROS triggered oxidative stress that perturbs the UPR balance leading to ER-stress. DOR activation retrieves the hUCB-BFs by ameliorating the levels of the UPR genes alongside a remarkable regulation of the apoptotic genes. Thus, oxidative stress and UPR, which has been shown to be profoundly connected, thereby resulting in apoptosis of hUCB-BFs, were potentially subsided on DOR activation using DADLE. Hence, DOR activation under the conditions of oxidative stress-induced cell-death on gaining in vivo relevance might prove helpful in increasing the viability of the hUCB-BFs and thereby, direct the way in the pursuit of successful tissue-specific hUCB-BFs regeneration and translational therapy (Fig. 5).
Source of funding Dwaipayan Sen is supported by a ‘Fast Track Young Scientist’ grant (YSS/2014/000027) from SERB, Department of Science and Technology (DST), Government of India and a start-up fund from VIT University, Vellore, India.
Conflict of interest
Introduction Myelomeningocele is a severe type of spina bifida that represents one of the most debilitating birth defects in humans (Copp et al., 2003; Copp and Greene, n.d.; Dias and McLone, 1993; Dias, 1999; Hunt, 1990; Lary and Edmonds, 1996; Meuli et al., 1997), with an estimated incidence of 3.3 in 10,000 live births. Myelomeningocele harshly affects both spinal cord and encephalic structures during gestation (Lary and Edmonds, 1996) resulting in disabilities that include paraplegia, skeletal deformities, hydrocephalus, hindbrain herniation, impaired mental development, and fecal, urinary, and sexual dysfunction (Dias and McLone, 1993; Dias, 1999; Hunt, 1990). A deficiency on primary neurulation leads to a deficient neural tube closure and myelomeningocele formation (Copp et al., 2003; Dias, 1999), which then induces the progressive neurodegeneration of the exposed spinal cord during pregnancy (Meuli et al., 1997). In humans, the two most common neural tube defects are myelomeningocele and myelocele; neural tissues are surrounded by a thin cystic sac in the former (spina bifida cystica) or exposed directly to the amniotic fluid in the latter (Copp and Greene, n.d). The myelomeningocele cyst around the exposed neural tissue contains CSF. When damaged or perforated during pregnancy, these contents can be released toward the amniotic space (Meuli and Moehrlen, 2014).