Extracellular Matrix-Based Biomaterials for Cardiovascular Tissue Engineering

Regenerative medicine and tissue engineering strategies have made remarkable progress in remodeling, replacing, and regenerating damaged cardiovascular tissues. The design of three-dimensional (3D) scaffolds with appropriate biochemical and mechanical characteristics is critical for engineering tissue-engineered replacements. The extracellular matrix (ECM) is a dynamic scaffolding structure characterized by tissue-specific biochemical, biophysical, and mechanical properties that modulates cellular behavior and activates highly regulated signaling pathways. In light of technological advancements, biomaterial-based scaffolds have been developed that better mimic physiological ECM properties, provide signaling cues that modulate cellular behavior, and form functional tissues and organs. In this review, we summarize the in vitro, pre-clinical, and clinical research models that have been employed in the design of ECM-based biomaterials for cardiovascular regenerative medicine. We highlight the research advancements in the incorporation of ECM components into biomaterial-based scaffolds, the engineering of increasingly complex structures using biofabrication and spatial patterning techniques, the regulation of ECMs on vascular differentiation and function, and the translation of ECM-based scaffolds for vascular graft applications. Finally, we discuss the challenges, future perspectives, and directions in the design of next-generation ECM-based biomaterials for cardiovascular tissue engineering and clinical translation.

A case report of an uncommon presentation of Nephroblastoma (Wilms tumor): in an older child with polycythemia and elevated erythropoietin

Introduction/Objective Wilms tumor (nephroblastoma), is a neoplasm that has a prevalence of 1 per 10,000 before the age of fifteen, with 50% occurring before age 3. WT1 (11p13) gene, a zinc finger transcription factor, is expressed in early urogenital system development and mutations here represent one of the primary pathways to the development of Wilms tumor. Although mouse model studies have shown that WT1 may be a transcriptional activator of erythropoietin (EPO) gene, increases in serum erythropoietin are rarely seen in patients with Wilms tumor. Concurrent polycythemia is a further rarity with only 11 such reports in literature. This is intriguing since WT1 mutations represent the most common mutation pathway in Wilms Tumor. Interestingly, other tumor types associated with elevated serum EPO and polycythemia (e.g. renal cell carcinoma and metanephric adenoma) are thought to do so through the generation of hypoxia inducible factor, and induction of VEGF. Methods/Case Report Here we present a case of Wilms tumor in a 7-year-old female who was establishing care after moving to Vermont. Physical examination showed possible splenomegaly ultimately discovered to be a large LUQ abdominal mass with a concurrent discovery of polycythemia. Subsequent serum EPO was 308 (Ref: 2.6-18.5 mIU/mL).). The mass was surgically removed with resolution of polycythemia. Histological evaluation showed a triphasic, blastema predominant Wilms tumor with favorable histology. Heterologous, vascular differentiation was seen in the stroma, positive for CD34 and CD31, and negative for D2-40. Results (if a Case Study enter NA) NA Conclusion Based on these findings, this phenomenon may be related to increased VEGF expression resulting in this patient’s increased serum EPO and polycythemia, and heterologous vascular differentiation within the tumor stroma. This is the first report of histology in a case of Wilms tumor associated with high serum EPO and polycythemia and may indicate an alternative pathway for the generation of EPO in Wilms tumor.

Comparative Vegetative, Nutritional and Anatomical Study of Two Almond Varieties Grafted on Bitter Almond and Nemaguard Peach Rootstocks

A comparative study was conducted during the 2017/2018 and 2018/2019 growing seasons for Nonpareil and Ne Plus Ultra almond cvs grafted on Bitter almond and Nemaguard peach rootstocks at the Experimental Research Station of National Research Centre at Nubaria, El Behera governorate, Egypt. The comparison was evaluated through the grafting success percentage, vegetative growth, determination of some leaf mineral composition, as well as, the anatomical examination of scion/rootstock union zone and cross-section of leaves. The obtained results clarified that the grafting success percentage was significantly affected by the different used rootstocks. Using Bitter almond rootstock recorded the highest percentage of grafting success, leaf chlorophyll content, root length, and a number of lateral root /plant in both cultivars. Using Nemaguard peach rootstock recorded significantly the highest values of scion length, stem girth above and below union zone, number of branches and leaves/plant, leaf area as well as seedlings fresh and dry weight. Leaves of both cultivars grafted on Nemaguard peach rootstock recorded the highest concentrations of leaf mineral contents as compared to those grafted on Bitter almond rootstock. Cross-sections of the graft union zone were taken after 28 days and 6 months from grafting for anatomical analysis. The callus cells developed 28 days after grafting, but cambial cells between the rootstock and scion tissues did not occur in all scion/rootstock combinations. After 6 months of grafting, cambial cells were established, vascular differentiation was observed, regular parenchymatic tissue properties and sclerenchyma bundles were seen in the graft union. There was no problem in terms of compatibility of Nonpareil and Ne Plus Ultra on Bitter almond and Nemaguard peach rootstocks. Comparing leaf cross-sections of almond grafted on both rootstocks demonstrated that the density of mesophyll cells was affected as a consequence of the rootstock–scion interaction. Nemaguard peach rootstock can be recommended for grafting Nonpareil and Ne Plus Ultra almond cultivars under Nubaria conditions to produce vigorous trees.

Aux/IAA and ARF Gene Families in Salix suchowensis: Identification, Evolution, and Dynamic Transcriptome Profiling During the Plant Growth Process

The phytohormone auxin plays a pivotal role in the regulation of plant growth and development, including vascular differentiation and tree growth. The auxin/indole-3-acetic acid (Aux/IAA) and auxin response transcription factor (ARF) genes are key components of plant auxin signaling. To gain more insight into the regulation and functional features of Aux/IAA and ARF genes during these processes, we identified 38 AUX/IAA and 34 ARF genes in the genome of Salix suchowensis and characterized their gene structures, conserved domains, and encoded amino acid compositions. Phylogenetic analysis of some typical land plants showed that the Aux/IAA and ARF genes of Salicaceae originated from a common ancestor and were significantly amplified by the ancestral eudicot hexaploidization event and the “salicoid” duplication that occurred before the divergence of poplar and willow. By analyzing dynamic transcriptome profiling data, some Aux/IAA and ARF genes were found to be involved in the regulation of plant growth, especially in the initial plant growth process. Additionally, we found that the expression of several miR160/miR167-ARFs was in agreement with canonical miRNA–ARF interactions, suggesting that miRNAs were possibly involved in the regulation of the auxin signaling pathway and the plant growth process. In summary, this study comprehensively analyzed the sequence features, origin, and expansion of Aux/IAA and ARF genes, and the results provide useful information for further studies on the functional involvement of auxin signaling genes in the plant growth process.

Transcriptional control of local auxin distribution by the CsDFB1-CsPHB module regulates floral organogenesis in cucumber

Plant cystatins are cysteine proteinase inhibitors that play key roles in defense responses. In this work, we describe an unexpected role for the cystatin-like protein DEFORMED FLORAL BUD1 (CsDFB1) as a transcriptional regulator of local auxin distribution in cucumber (Cucumis sativus L.). CsDFB1 was strongly expressed in the floral meristems, floral primordia, and vasculature. RNA interference (RNAi)-mediated silencing of CsDFB1 led to a significantly increased number of floral organs and vascular bundles, together with a pronounced accumulation of auxin. Conversely, accompanied by a decrease of auxin, overexpression of CsDFB1 resulted in a dramatic reduction in floral organ number and an obvious defect in vascular patterning, as well as organ fusion. CsDFB1 physically interacted with the cucumber ortholog of PHABULOSA (CsPHB), an HD-ZIP III transcription factor whose transcripts exhibit the same pattern as CsDFB1. Overexpression of CsPHB increased auxin accumulation in shoot tips and induced a floral phenotype similar to that of CsDFB1-RNAi lines. Furthermore, genetic and biochemical analyses revealed that CsDFB1 impairs CsPHB-mediated transcriptional regulation of the auxin biosynthetic gene YUCCA2 and the auxin efflux carrier PIN-FORMED1, and thus plays a pivotal role in auxin distribution. In summary, we propose that the CsDFB1-CsPHB module represents a regulatory pathway for local auxin distribution that governs floral organogenesis and vascular differentiation in cucumber.