CREAM(ToolGen)

Mesenchymal stem cells (MSCs) have emerged as novel therapies for supporting arteriovenous fistula (AVF) maturation, and bioresorbable polymeric scaffolds have enabled sustained MSC delivery into maturing AVFs. However, the radiolucency of biopolymeric wraps prevents in vivo monitoring of their integrity and location, hindering long-term preclinical investigations.

We infused bismuth nanoparticles (BiNPs) into polycaprolactone (PCL) to fabricate an electrospun perivascular wrap capable of MSC delivery and conducive to longitudinal monitoring using conventional imaging. We tested the wraps' effects on the attenuation of markers of neointimal hyperplasia (i.e., endothelial dysfunction, hypoxia, and inflammation), the leading cause of AVF failure, in rats with induced chronic kidney disease (n = 3 per time point) for the following groups: control (no wrap), PCL wrap, PCL with MSCs, PCL-Bi (BiNP-infused wrap), and PCL-Bi with MSCs.

Physicochemical characterization and in vitro biocompatibility tests revealed that BiNP infusion did not alter the wrap's non-cytotoxicity toward vascular cells, hemocompatibility, and capacity for MSC loading but facilitated long-term monitoring via micro-computed tomography. After 8 weeks, all treatment groups demonstrated significant improvement in wall-to-lumen ratio on ultrasonography (P < 0.001), neointima-to-lumen ratio on histomorphometry (P < 0.001), and attenuation of neointimal hypoxia on immunohistochemistry (P < 0.05). Compared to non-MSC wraps, MSC-loaded wraps not only attenuated endothelial dysfunction and neointimal inflammation but also reduced hypoxia and inflammation across all vascular layers.

These results demonstrate that MSC delivery through a radiopaque polymeric wrap could enhance AVF patency outcomes through the inhibition of multiple pathways inducing AVF failure.

Background: The ability of mesenchymal stromal cells (MSCs) to facilitate regenerative responses in inflamed and injured tissues, coupled with preclinical data suggesting potential to restore defective collagen VII at the dermo-epidermal junction, has raised the hope that MSCs may provide an effective disease-modifying therapy for patients suffering from recessive dystrophic epidermolysis bullosa (RDEB).Methods: We present a descriptive analysis of the clinical research on systemic MSC administration to RDEB patients available in PubMed, including six early-phase studies and one case report, involving 59 patients who received 1-3 intravenous infusions of MSCs from various sources.Results: Based on 133 MSC infusions, a total of 44 mostly mild adverse events were reported as definitely, possibly or likely related to the study treatment, only two of which led to treatment discontinuation. Improvements were seen in skin manifestations, disease activity, pain, pruritus and quality of life, with considerable heterogeneity in reported outcome variables and measurement tools between studies, and large inter-patient variability within studies.Conclusions: Although the current evidence base is limited, reflecting the typical challenges of clinical research in rare diseases, the reported results suggest potential treatment benefits for patients and provide a rationale for continuing to pursue this therapeutic approach.