Explant-derived human dental pulp stem cells enhance differentiation and proliferation potentials

Numerous stem cell niches are present in the different tissues and organs of the adult human body. Among these tissues, dental pulp, entrapped within the 'sealed niche' of the pulp chamber, is an extremely rich site for collecting stem cells. In this study, we demonstrate that the isolation of human dental pulp stem cells by the explants culture method (hD-DPSCs) allows the recovery of a population of dental mesenchymal stem cells that exhibit an elevated proliferation potential. Moreover, we highlight that hD-DPSCs are not only capable of differentiating into osteoblasts and chondrocytes but are also able to switch their genetic programme when co-cultured with murine myoblasts. High levels of MyoD expression were detected, indicating that muscle-specific genes in dental pulp cells can be turned on through myogenic fusion, confirming thus their multipotency. A perivascular niche may be the potential source of hD-DPSCs, as suggested by the consistent Ca(2+) release from these cells in response to endothelin-1 (ET-1) treatment, which is also able to significantly increase cell proliferation. Moreover, response to ET-1 has been found to be superior in hD-DPSCs than in DPSCs, probably due to the isolation method that promotes release of stem/progenitor cells from perivascular structures. The ability to isolate, expand and direct the differentiation of hD-DPSCs into several lineages, mainly towards myogenesis, offers an opportunity for the study of events associated with cell commitment and differentiation. Therefore, hD-DPSCs display enhanced differentiation abilities when compared to DPSCs, and this might be of relevance for their use in therapy

The remission clinic approach to halt the progression of kidney disease

Randomized multicenter studies in diabetic and nondiabetic patients with chronic proteinuric nephropathies have clearly demonstrated that renin-angiotensin system (RAS) inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) used alone or in combination, effectively retard renal disease progression. Proteinuria reduction, in addition to arterial blood pressure control, largely mediates the nephroprotective effect of RAS inhibitor therapy. Despite RAS inhibition, however, most patients with chronic kidney disease (CKD) progress to end-stage renal disease (ESRD). This highlights the importance of innovative therapies to halt or revert CKD progression in those at risk. Along this line, a multimodal strategy (Remission Clinic) targeting urinary proteins by dual RAS inhibition with ACE inhibitors and ARBs up-titrated to maximum tolerated doses, by intensified blood pressure control, amelioration of dyslipidemia by statins, smoking cessation and healthy lifestyle implementation was safely and effectively applied at our outpatient clinic to normalize urinary proteins and prevent renal function loss in patients otherwise predicted to rapidly progress to ESRD because of nephrotic-range proteinuria refractory to standard antihypertensive dosages of an ACE inhibitor. This approach achieved remission or regression of proteinuria and stabilized kidney function in most cases, and almost fully prevented progression to ESRD. Provided patients are closely monitored and treatment is cautiously up-titrated according to tolerability, this approach might be safely applied in day-by-day hospital practice. Effective prevention of ESRD would reduce costs of renal replacement therapy by dialysis or transplantation and would be life-saving where these are not available for all patients in need

A novel biomarker harvesting nanotechnology identifies Bak as a candidate melanoma biomarker in serum.

Melanoma represents only 4\% of all skin cancers, but nearly 80\% of skin cancer deaths. This manuscript applies several new measurement technologies with the purpose of elucidating molecular signatures of melanoma aggressiveness.We sought to determine whether low-abundant serum proteins related to apoptotic pathways could be measured and correlated with defined melanoma subtypes. Hydrogel core shell nanoparticles, a new technology capable of selectively entrapping low molecular weight proteins and protecting them from enzymatic degradation, were used to capture candidate serum biomarkers. Biomarker levels were correlated with confocal microscopy, thereby representing a combination of new technologies for in vivo histologic documentation.Among a panel of analyzed serum proteins, Bak was differentially expressed between nevi and melanomas. Melanomas with higher Bak serum levels exhibited more pronounced junctional activity on confocal imaging, whereas lesions with 'sparse' dermal nests had weak Bak expression.Our study links serum proteome analysis with confocal microscopic clinical in vivo histologic classification of melanomas. Bak has not been previously measured in serum. Bak differential expression among melanoma subtypes confirms the importance of the apoptotic pathway as a contributor to melanoma aggressiveness