Metabolism as an early predictor of DPSCs aging.

Tissue resident adult stem cells are known to participate in tissue regeneration and repair that follows cell turnover, or injury. It has been well established that aging impedes the regeneration capabilities at the cellular level, but it is not clear if the different onset of stem cell aging between individuals can be predicted or prevented at an earlier stage. Here we studied the dental pulp stem cells (DPSCs), a population of adult stem cells that is known to participate in the repair of an injured tooth, and its properties can be affected by aging. The dental pulp from third molars of a diverse patient group were surgically extracted, generating cells that had a high percentage of mesenchymal stem cell markers CD29, CD44, CD146 and Stro1 and had the ability to differentiate into osteo/odontogenic and adipogenic lineages. Through RNA seq and qPCR analysis we identified homeobox protein, Barx1, as a marker for DPSCs. Furthermore, using high throughput transcriptomic and proteomic analysis we identified markers for DPSC populations with accelerated replicative senescence. In particular, we show that the transforming growth factor-beta (TGF-ß) pathway and the cytoskeletal proteins are upregulated in rapid aging DPSCs, indicating a loss of stem cell characteristics and spontaneous initiation of terminal differentiation. Importantly, using metabolic flux analysis, we identified a metabolic signature for the rapid aging DPSCs, prior to manifestation of senescence phenotypes. This metabolic signature therefore can be used to predict the onset of replicative senescence. Hence, the present study identifies Barx1 as a DPSCs marker and dissects the first predictive metabolic signature for DPSCs aging.

Clinical Applications of Induced Pluripotent Stem Cells - Stato Attuale.

In an adult human body, somatic stem cells are present in small amounts in almost all organs with the function of general maintenance and prevention of premature aging. But, these stem cells are not pluripotent and are unable to regenerate large cellular loss caused by infarctions or fractures especially in cells with limited replicative ability such as neurons and cardiomyocytes. These limitations gave rise to the idea of inducing pluripotency to adult somatic cells and thereby restoring their regeneration, replication and plasticity. Though many trials and research were focused on inducing pluripotency, a solid breakthrough was achieved by Yamanaka in 2006. Yamanaka's research identified 4 genes (OCT-4, SOX-2, KLF-4 and c-MYC) as the key requisite for inducing pluripotency in any somatic cells (iPSCs). Our study, reviews the major methods used for inducing pluripotency, differentiation into specific cell types and their application in both cell regeneration and disease modelling. We have also highlighted the current status of iPSCs in clinical applications by analysing the registered clinical trials. We believe that this review will assist the researchers to decide the parameters such as induction method and focus their efforts towards clinical application of iPSCs.

Eminent Sources of Adult Mesenchymal Stem Cells and Their Therapeutic Imminence.

In the recent times, stem cell biology has garnered the attention of the scientific fraternity and the general public alike due to the immense therapeutic potential that it holds in the field of regenerative medicine. A breakthrough in this direction came with the isolation of stem cells from human embryo and their differentiation into cell types of all three germ layers. However, the isolation of mesenchymal stem cells from adult tissues proved to be advantageous over embryonic stem cells due to the ethical and immunological naivety. Mesenchymal Stem Cells (MSCs) isolated from the bone marrow were found to differentiate into multiple cell lineages with the help of appropriate differentiation factors. Furthermore, other sources of stem cells including adipose tissue, dental pulp, and breast milk have been identified. Newer sources of stem cells have been emerging recently and their clinical applications are also being studied. In this review, we examine the eminent sources of Mesenchymal Stem Cells (MSCs), their immunophenotypes, and therapeutic imminence.