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Graphical Abstracts



Confocal picture showing the myelinogenic potential of hiPS-NSCs engrafted at the border between the striatum and the corpus callosum of immunodeficient MLD mice at 3 months post-transplantation(green, human cells labeled with anti-human mitochondria; red, myelin basic protein; blue, nuclei counterstained with ToPro3). Scale bar: 100µm.

An ex vivo culture system used to isolate scalable quantities of hS/PCs with consistent expression of progenitor markers, is reported here. These hS/PCs can be maintained in long-term culture in 2D or in 3D, without loss of stem/progenitor markers.  Incorporation of bioactive basement membrane-derived peptides in the 3D hyaluronate (HA) hydrogel culture system enhances progenitor expansion.  Stimulation of hS/PC spheroids with neurotransmitter agonists leads to differentiation toward an acinar lineage.

Stem cells are emerging as a scientifically plausible treatment and possible cure for cerebral palsy, but are not yet proven. The lack of valid animal models has significantly hampered the scope of clinical trials. Despite the state of current treatment evidence, parents remain optimistic about the potential improvements from stem cell intervention and feel compelled to exhaust all therapeutic options, including stem cell tourism. Receiving unproven therapies from unvalidated sources is potentially dangerous. Thus it is essential that researchers and clinicians stay up to date. A systematic review and meta-analysis summarizing and aggregating current research data may provide more conclusive evidence to inform treatment decision making and help direct future research.

At 1 hour post- traumatic spinal cord injury (SCI), 2.5 million human stromal cells (human umbilical cord matrix cells, HUCMCs; or human brain vascular pericytes, HBVPs) were systemically infused via the tail vein (A). While a majority of cells ended up in the lungs, liver and spleen, the spleen was found to be the site of IL-10 synthesis/release (B). Systemic changes in IL-10 were associated with decreased blood-spinal cord barrier (BSCB) permeability and reduced spinal cord hemorrhage at acute time-points (C). Weekly-standardized behavioural testing revealed that the early protective effects of cell infusion lead to some improvements in functional recovery (D). Together, these data warrant further study of the splenic role in secondary pathology and cell-based reparative mechanisms for future clinical translation.

Brown adipose pads are present in the interscapular region of human fetus. Tissue sections from a representative fetus (12 week gestation). Hematoxylin-eosin staining of fetal interscapular adipose tissue revealed the presence of some dispersed cells with a multilocular aspect, characteristic of brown adipocytes (A–C, arrowheads). Immunohistochemistry on serial sections confirmed the brown nature of the multilocular cells which were positive for the brown marker uncoupling-protein-1 (UCP-1) (E–F). Negative control with unstained multilocular cells (D, arrowheads). Magnification: (A): × 10; (B, D, E): × 20; (C): × 40; (F): × 60.

Pluripotency marker expression after manipulation of microchamber geometry (height). Microchamber height was scaled to increase local volume and deplete concentrations of cell-secreted factors. Mouse embryonic stem cells cultured inside microfluidic chambers for 3 days showed decreased pluripotency and increased scattering phenotype with increasing chamber height. Please note that cartoon of microchambers is stylized. In real devices only the channel height was varied while the thickness of the roof was kept constant. Scale bar: 100 µm.

Clinical significance of Sca-1 in human gastric cancer. Clinical significance of Sca-1 in human gastric cancer. (A): A hierarchical clustering dendrogram for pretreatment biopsy samples of chemotherapy-treated gastric cancer patients, which was generated using genes overexpressed in Sca-1high S1 cells (Sca-1 signature). Red and green denotes high and low gene expression levels, respectively. (B): Kaplan-Meier plots for overall survival of 2 clusters generated by (A). Patients who overexpressed genes in the Sca-1 signature had significantly shorter overall survival (Log-rank, p = .005). Red and black lines denote Kaplan-Meir plots for clusters with high- and low-expression of genes in the Sca-1 signature, respectively.

Association of Prx II with cancer stem cell in HCC cells. (A): Representative image of EpCAM(+)/K19(+) HCC showing Prx II expression in contrast to EpCAM(−)/K19(−) HCC without expression of Prx II (magnification, × 200). (B): Comparison of proportions of Prx II expressing in EpCAM(+)/K19(+) HCCs and EpCAM(−)/K19(−) HCCs. (C): Expression levels of Sox2 in Huh7 cells transfected with siPrx II. (D): Proportions of 2′,7′-dichlorodihydrofluorescein diacetate, annexin V, EpCAM, and CD133 positive in Huh7 cells transfected with siPrx II by flow cytometric analysis. The data are the mean ± SEM (n = 5 per group), *p < .05. Abbreviations: EpCAM, epithelial-cell adhesion molecules; HCC, hepatocellular carcinoma; Prx II, peroxiredoxin II; K19, cytokeratin 19.

Schematic highlighting promising primary and adjunctive neuroregenerative strategies for traumatic spinal cord injury. Transplanted autogenic and allogenic cells can differentiate to oligodendrocytes to remyelinate denuded axons (1), neurons to restore functional neural circuits (2), or can be modified to express critical pro-regenerative factors to positively modulate the microenvironment (8). Multipotent cells can also be mobilized from endogenous cell pools, particularly the central canal, to facilitate recovery (5). Both exogenous and endogenous regeneration may be further bolstered by providing molecular signalling to direct axon regrowth (3), enhancing synaptic plasticity (4), providing a structural framework for engraftment (e.g. biomaterials) (6), and/or degrading the inhibitory glial scar (7).