MSCs derived extracellular vesicles as a therapeutic paragon for neurodegenerative disorders: A viewpoint

Neurodegenerative disorders are a vicious woe to the public health and wellness. Uncertainty in their underlying causes, lack of effective biomarkers for their early detection, existence of only supportive therapy, and their ever rising incidence creates an unmatched need for targeted therapies. Mesenchymal Stem Cells (MSCs) have found to be promising candidates for regenerative and remedial therapy in neurodegenerative disorders, however several biological risks and practical issues impede in their translational utility. Deriving from MSCs are certain Extracellular Vesicles (EVs), which aid in the paracrine action of MSCs and have lately gained the scientific interest for their implacability in diverse set ups. Their cargo is of utmost importance and is being explored in various different diseases like heart diseases, neuronal diseases, respiratory diseases and hepatic diseases. They thereby hold the position of a likely prospective remedial candidate for therapy against neurodegenerative disorders.     

Basal cell carcinoma stem cells exhibit osteogenic and chondrogenic differentiation potential

Specific cell subpopulations identified as cancer stem cells (CSCs) can be found in basal cell carcinoma (BCC). Generally, CSCs have a marked trans-differentiation potential that could potentially be used in differentiation therapies. However, there are no studies regarding BCC CSCs multipotency. The aim of the study was to analyze the characteristic of CSCs of BCC with emphasis on their differentiation potential upon specific induction. Specific staining and cell morphology were used for differentiation confirmation, along with the expression analysis of osteogenic (ALP, BSP, Runx2, OCN, BMP2), chondrogenic (COL1 and COL2A1), adipogenic (PPAR-γ) and neurogenic (Nestin and MAP2) markers. BCC CSCs differentiated into osteogenic and chondrogenic lineages, as judged by staining and high expression of specific markers (from 2-to 92-fold higher upon induction). Concomitantly with differentiation, the levels of cancer stem cell markers decreased in the cultures. Adipo-differentiation and neuro-differentiation were unsuccessful. In conclusion, BCC CSCs exhibit the capacity to trans-differentiate, a characteristic that may potentially be useful in the development of new strategies for the treatment of aggressive BCCs.     

Mesenchymal stem cells: As a multi-target cell therapy for clearing β-amyloid deposition in Alzheimer’s disease

Extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks of Alzheimer’s disease (AD). Studies have shown that aggregates of extracellular Aβ can induce neuroinflammation mediated neurotoxic signaling through microglial activation and release of pro-inflammatory factors. Thus, modulation of Aβ might be a potential therapeutic strategy for modifying disease progression. Recently, a large number of reports have confirmed the beneficial effects of mesenchymal stem cells (MSCs) on AD. It is believed to reduce neuroinflammation, reduce Aβ amyloid deposits and NFTs, increase acetylcholine levels, promote neurogenesis, reduce neuronal damage, and improve working memory and cognition. In this review, we focus on the role of MSCs in clearing Aβ deposition. MSCs have the potential to modulate Aβ-related microenvironments via enhancement of autophagy, proteolysis of Aβ aggregates, phagocytic clearance of Aβ by microglial M2 polarization, decrease oxidative stress (OS), and correction of abnormal sphingolipid (SL) metabolism. With advantages in clinical applications, these data suggest that the use of MSCs as a multi-target modulator of Aβ would be an effective therapeutic approach in AD.     

Response of donor and recipient cells after transplantation of cells to the ligament and tendon

The mechanical properties of healing ligaments and tendons are not comparable to those of normal tissue. To improve the quality of the ligament healing, therapeutic strategies include gene transfer or placement of mesenchymal stem cells at the healing site. Studies show that marker genes, growth factors, and antisense oligonucleotides can be delivered to both normal and healing ligaments and tendons by gene transfer. Cells with and without genetic modification have been successfully transplanted to ligaments and tendons and remain viable. Tendon healing can be improved using collagen gel implants seeded with autologous mesenchymal stem cells. Even though these early results are encouraging, more work is required regarding the response of the recipient site to donor cells or vectors.     

Serial section reconstruction using a computer graphics system: Applications to intracellular structures in yeast cells and to the periodontal structure of dogs' teeth

A computer graphics system for reconstruction from serial section micrographs was applied to intracellular details of a yeast target cell (Saccharomyces cerevisiae cell) induced by the α factor mating pheromone and was also applied to a periodontal structure of a dog tooth moved orthodontically. In the former, intracellular organelles and a distribution of vesicles could be clearly observed through the cell membrane using the transparent display method in which the smoothing of the reconstructed outer cell membrane surface by computer processing was applied to the transparent display. In the latter case, by cutting through a reconstructed dog tooth and its periodontal tissues, labiolingual and mesiodistal cut surfaces of the tooth and of adjacent alveolar bone could be observed with fine details (232 sections were used).     

Phenotypic,morphological, and metabolic characterization of vascular-spheres from human vascular mesenchymal stem cells

The ability to form spheroids under non-adherent conditions is a well-known property of human mesenchymal stem cells (hMSCs), in addition to stemness and multilineage differentiation features. In the present study, we tested the ability of hMSCs isolated from the vascular wall (hVW-MSCs) to grow as spheres, and provide a characterization of this 3D model. hVW-MSCs were isolated from femoral arteries through enzymatic digestion. Spheres were obtained using ultra-low attachment and hanging drop methods. Immunophenotype and pluripotent genes (SOX-2, OCT-4, NANOG) were analyzed by immunocytochemistry and real-time PCR, respectively. Spheres histological and ultrastructural architecture were examined. Cell viability and proliferative capacity were measured using LIVE/DEATH assay and ki-67 proliferation marker. Metabolomic profile was obtained with liquid chromatography–mass spectrometry. In 2D, hVW-MSCs were spindle-shaped, expressed mesenchymal antigens, and displayed mesengenic potential. 3D cultures of hVW-MSCs were CD44⁺, CD105^low, CD90^low, exhibited a low propensity to enter the cell cycle as indicated by low percentage of ki-67 expression and accumulated intermediate metabolites pointing to slowed metabolism. The 3D model of hVW-MSCs exhibits stemness, dormancy and slow metabolism, typically observed in stem cell niches. This culture strategy can represent an accurate model to investigate hMSCs features for future clinical applications in the vascular field.     

Bones Morphogenic Protein‐4 and retinoic acid combined treatment comparative analysis for in vitro differentiation potential of murine mesenchymal stem cells derived from bone marrow and adipose tissue into germ cells

Nowadays, infertility is no longer considered as an unsolvable disorder due to progresses in germ cells derived from stem lineage with diverse origins. Technical and ethical challenges push researchers to investigate various tissue sources to approach more efficient gametes. The purpose of the current study is to investigate the efficacy of a combined medium, retinoic acid (RA) together with Bone Morphogenic Protein‐4 (BMP4), on differentiation of Bone Marrow Mesenchymal Stem Cells (BMMSCs) and adipose‐derived mesenchymal stem cells (ADMSCs) into germ cells. Murine MSCs were obtained from both Bone Marrow (BM) and Adipose Tissue (AT) samples and were analyzed for surface markers to get further verification of their nature. BMMSCs and ADMSCs were induced into osteogenic and adipogenic lineage cells respectively, to examine their multipotency. They were finally differentiated into germ cells using media enriched with BMP4 for 4 days followed by addition of RA for 7 days (11 days in total). Analyzing of differentiation potential of BMMSCs‐ and ADMSCs were performed via Immunofluorescence, Flowcytometry and Real time‐PCR techniques for germ cell‐specific markers (Mvh, Dazl, Stra8 and Scp3). Mesenchymal surface markers (CD90 and CD44) were expressed on both BMMSCs and ADMSCs, while endothelial and hematopoietic cell markers (CD31 and CD45) had no expression. Finally, all germ‐specific markers were expressed in both BM and AT. Although germ cells differentiated from ADMSCs showed faster growth and proliferation as well as easy collection, they significantly expressed germ‐specific markers lower than BMMSCs. This suggests stronger differentiation potential of murine BMMSCs than ADMSCs.     

Neural stem cell-conditioned medium upregulated the PCMT1 expression and inhibited the phosphorylation of MST1 in SH-SY5Y cells induced by Aβ_25-35

A progressive neurodegenerative disease, Alzheimer’s disease (AD). Studies suggest that highly expressedprotein isoaspartate methyltransferase 1 (PCMT1) in brain tissue. In the current study, we explored the effects ofneural stem cell-conditioned medium (NSC-CDM) on the PCMT1/MST1 pathway to alleviate Aβ_25-35-induceddamage in SH-SY5Y cells. Our data suggested that Aβ25-35 markedly inhibited cell viability. NSC-CDM or Neuralstem cell-complete medium (NSC-CPM) had a suppression effect on toxicity when treatment with Aβ_25-35, with agreater effect observed with NSC-CDM. Aβ_25-35 + NSC-CDM group exhibited an increase in PCMT1 expression.sh-PCMT1 markedly decreased cell proliferation and suppressed the protective role of NSC-CDM through theinduction of apoptosis and improved p-MST1 expression. Overexpression of PCMT1 reversed the Aβ_25-35-induceddecrease in cell proliferation and apoptosis. In summary, our findings suggest that NSC-CDM corrects the Aβ_25-35-induced damage to cells by improving PCMT1 expressions, which in turn reduces phosphorylation of MST1.