Multipotent mesenchymal stromal cells (MSCs) represent a rare heterogeneous subset of pluripotent stromal cells that can be isolated from many different adult tissues that exhibit the potential to ...give rise to cells of diverse lineages. Numerous studies have reported beneficial effects of MSCs in tissue repair and regeneration. After culture expansion and in vivo administration, MSCs home to and engraft to injured tissues and modulate the inflammatory response through synergistic downregulation of proinflammatory cytokines and upregulation of both prosurvival and antiinflammatory factors. In addition, MSCs possess remarkable immunosuppressive properties, suppressing T‐cell, NK cell functions, and also modulating dentritic cell activities. Tremendous progress has been made in preclinical studies using MSCs, including the ability to use allogeneic cells, which has driven the application of MSCs toward the clinical setting. This review highlights our current understanding into the biology of MSCs with particular emphasis on the cardiovascular and renal applications, and provides a brief update on the clinical status of MSC‐based therapy. STEM CELLS 2010;28:585–596
Trace DNA is a significant type of evidence for its ability to be collected from touched items or surfaces at crime scenes to link suspects to their crimes. In cases of violent crimes like assault, ...sexual offences, or even homicide, often touch DNA is collected from the victim’s skin. However, the collection of touch DNA from the victim’s skin can be complex because of the mixture of DNA present, as there is likely to be a small quantity of the offender’s DNA compared to the victim’s DNA. Validating different collection methods or techniques can improve touch DNA sampling; therefore, this study investigated three collection techniques involving cotton and nylon swabs to test their efficiency for the collection of touch DNA from the human neck. There was a significant difference between the three recovery techniques used to recover touch DNA with a cotton swab (CS) (
p
< 0.05) and nylon swab (NS) (
p
< 0.05), with more alleles observed when the neck skin was moistened with 100 μL of distilled water using a spray bottle before collection with both swabs.
Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a significant concern in the camel population of Saudi Arabia. This study aimed to provide epidemiological insights ...into the disease by estimating the true prevalence in camels in the Eastern Province and Riyadh, using a Bayesian estimation framework, and exploring the associated risk factors through a frequentist approach. A total of 1200 camel blood samples were collected and analyzed using an indirect ELISA method. The true herd-level prevalence was estimated at 0.7 (95% probability interval: 0.57 to 0.81), and the mean expected true animal-level prevalence was 0.17 (0.14 to 0.20). Risk factors associated with Map seropositivity were identified, including sex, breed, raising system, and production type. Females, single breed camels, and nomadic raising systems were found to have lower odds of seropositivity, while camels used for racing and show had significantly higher odds. The study's Bayesian approach, adjusting for the imperfect accuracy of MAP tests, provides a nuanced understanding of the disease's prevalence in the region. The integration of true prevalence estimates with risk factor analysis offers a comprehensive framework that can guide future policies and strategies in the fight against paratuberculosis in Saudi Arabia. The findings emphasize the importance of targeted control measures, underscoring the urgent need for interventions in Saudi Arabia's camel population. By understanding the true disease prevalence and its associated risk factors, we can enhance disease management strategies, offering valuable insights for future control and eradication efforts in the region.
The current need for organ and tissue replacement, repair, and regeneration for patients is continually growing such that supply is not meeting demand primarily due to a paucity of donors as well as ...biocompatibility issues leading to immune rejection of the transplant. In order to overcome these drawbacks, scientists have investigated the use of scaffolds as an alternative to transplantation. These scaffolds are designed to mimic the extracellular matrix (ECM) by providing structural support as well as promoting attachment, proliferation, and differentiation with the ultimate goal of yielding functional tissues or organs. Initial attempts at developing scaffolds were problematic and subsequently inspired an interest in 3D printing as a mode for generating scaffolds. Utilizing three‐dimensional printing (3DP) technologies, ECM‐like scaffolds can be produced with a high degree of complexity, where fine details can be included at a micrometer level. In this Review, the criteria for printing viable and functional scaffolds, scaffolding materials, and 3DP technologies used to print scaffolds for tissue engineering are discussed. Creating biofunctional scaffolds could potentially help to meet the demand by patients for tissues and organs without having to wait or rely on donors for transplantation.
The generation of scaffolds using 3D printing technologies is set to become a tangible option for a broad spectrum of patients in need of new tissues or organs. Bioengineers and clinicians are collaborating to create 3D printed scaffolds to mimic the local architecture of specific tissues at an intricate level. This Review gives an overview of the advancements made in 3D printing for tissue regeneration and compares the advantages and disadvantages of the different printing technologies and materials used.
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Large bone defects are usually managed by replacing lost bone with non-biological prostheses or with bone grafts that come from the patient or a donor. Bone tissue engineering, as a ...field, offers the potential to regenerate bone within these large defects without the need for grafts or prosthetics. Such therapies could provide improved long- and short-term outcomes in patients with critical-sized bone defects. Bone tissue engineering has long relied on the administration of growth factors in protein form to stimulate bone regeneration, though clinical applications have shown that using such proteins as therapeutics can lead to concerning off-target effects due to the large amounts required for prolonged therapeutic action. Gene-based therapies offer an alternative to protein-based therapeutics where the genetic material encoding the desired protein is used and thus loading large doses of protein into the scaffolds is avoided. Gene- and RNAi-activated scaffolds are tissue engineering devices loaded with nucleic acids aimed at promoting local tissue repair. A variety of different approaches to formulating gene- and RNAi-activated scaffolds for bone tissue engineering have been explored, and include the activation of scaffolds with plasmid DNA, viruses, RNA transcripts, or interfering RNAs. This review will discuss recent progress in the field of bone tissue engineering, with specific focus on the different approaches employed by researchers to implement gene-activated scaffolds as a means of facilitating bone tissue repair.
Objectives
To evaluate the effect of non-viral gene therapy on human dental pulp stem cells (DPSCs) in an in vitro and an ex vivo model.
Materials and methods
Nanoplexes comprising polyethyleneimine ...(PEI) and plasmid DNA (pDNA) encoding for fibroblast growth factor-2 (p
FGF-2
) and bone morphogenic protein-2 (p
BMP-2
) were cultured with DPSCs to evaluate cytotoxicity, protein expression, and mineralization activity. Collagen scaffolds loaded with these nanoplexes or mineral trioxide aggregate (MTA) were utilized in an ex vivo tooth culture model to assess pulp response, over a period of 14 days. All nanoplex formulations were characterized for size and zeta potential by measuring dynamic light scattering and electrophoretic mobility, respectively.
Results
DPSCs treated with the nanoplexes showed increased cell proliferation and enhanced expression of BMP-2 and FGF-2 proteins. Collagen scaffolds containing PEI-p
BMP-2
and/or p
FGF-2
nanoplexes significantly increased cell proliferation, BMP-2 and FGF-2 expression, and mineralization when compared to MTA. Ex vivo histology showed a well-preserved pulp and healthy tissue in both the MTA and scaffold groups. Connective tissue in contact with the scaffold was dense and homogeneous, with some cells present in contact and within the scaffold.
Conclusion
Transfection of DPSCs with p
BMP-2
/p
FGF-2
nanoplexes resulted in increased expression of BMP-2 and FGF-2, enhanced proliferation, and mineralization properties compared to MTA. These findings were supported by the ex vivo observations.
Clinical relevance
This biological approach in pulp capping brings new insights into the effective management of engineered pulp tissues, mainly those generated by the transplantation of DPSCs in empty root canals.
Clear cell renal cell carcinoma (ccRCC) is one of the most immunologically distinct tumor types due to high response rate to immunotherapies, despite low tumor mutational burden. To characterize the ...tumor immune microenvironment of ccRCC, we applied single-cell-RNA sequencing (SCRS) along with T-cell-receptor (TCR) sequencing to map the transcriptomic heterogeneity of 25,688 individual CD45
lymphoid and myeloid cells in matched tumor and blood from three patients with ccRCC. We also included 11,367 immune cells from four other individuals derived from the kidney and peripheral blood to facilitate the identification and assessment of ccRCC-specific differences. There is an overall increase in CD8
T-cell and macrophage populations in tumor-infiltrated immune cells compared to normal renal tissue. We further demonstrate the divergent cell transcriptional states for tumor-infiltrating CD8
T cells and identify a MKI67 + proliferative subpopulation being a potential culprit for the progression of ccRCC. Using the SCRS gene expression, we found preferential prediction of clinical outcomes and pathological diseases by subcluster assignment. With further characterization and functional validation, our findings may reveal certain subpopulations of immune cells amenable to therapeutic intervention.
Liquid biopsies including circulating tumor cells (CTCs) and cell-free DNA (cfDNA) have enabled minimally invasive characterization of many cancers, but are rarely analyzed together. Understanding ...the detectability and genomic concordance of CTCs and cfDNA may inform their use in guiding cancer precision medicine. Here, we report the detectability of cfDNA and CTCs in blood samples from 107 and 56 patients with multiple myeloma (MM), respectively. Using ultra-low pass whole-genome sequencing, we find both tumor fractions correlate with disease progression. Applying whole-exome sequencing (WES) to cfDNA, CTCs, and matched tumor biopsies, we find concordance in clonal somatic mutations (~99%) and copy number alterations (~81%) between liquid and tumor biopsies. Importantly, analyzing CTCs and cfDNA together enables cross-validation of mutations, uncovers mutations exclusive to either CTCs or cfDNA, and allows blood-based tumor profiling in a greater fraction of patients. Our study demonstrates the utility of analyzing both CTCs and cfDNA in MM.
Selenium has been extensively evaluated clinically as a chemopreventive agent with variable results depending on the type and dose of selenium used. Selenium species are now being therapeutically ...evaluated as modulators of drug responses rather than as directly cytotoxic agents. In addition, recent data suggest an association between selenium base-line levels in blood and survival of patients with COVID-19. The major focus of this mini review was to summarize: the pathways of selenium metabolism; the results of selenium-based chemopreventive clinical trials; the potential for using selenium metabolites as therapeutic modulators of drug responses in cancer (clear-cell renal-cell carcinoma (ccRCC) in particular); and selenium usage alone or in combination with vaccines in the treatment of patients with COVID-19. Critical therapeutic targets and the potential role of different selenium species, doses, and schedules are discussed.
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