Sebastian Beyer

Not All MSCs Can Act as Pericytes: Functional In Vitro Assays to Distinguish Pericytes from Other Mesenchymal Stem Cells in Angiogenesis.

Pericytes play a crucial role in angiogenesis and vascular maintenance. They can be readily identified in vivo and isolated as CD146(+)CD34(-) cells from various tissues. Whether these and other markers reliably identify pericytes in vitro is unclear. CD146(+)CD34(-) selected cells exhibit multilineage potential. Thus, their perivascular location might represent a stem cell niche. This has spurred assumptions that not only all pericytes are mesenchymal stromal cells (MSCs), but also that all MSCs can act as pericytes. Considering this hypothesis, we developed functional assays by confronting test cells with endothelial cultures based on matrigel assay, spheroid sprouting, and cord formation. We calibrated these assays first with commercial cell lines [CD146(+)CD34(-) placenta-derived pericytes (Pl-Prc), bone marrow (bm)MSCs and fibroblasts]. We then functionally compared the angiogenic abilities of CD146(+)CD34(-)selected bmMSCs with CD146(-) selected bmMSCs from fresh human bm aspirates. We show here that only CD146(+)CD34(-) selected Pl-Prc and CD146(+)CD34(-) selected bmMSCs maintain endothelial tubular networks on matrigel and improve endothelial sprout morphology. CD146(-) selected bmMSCs neither showed these abilities, nor did they attain pericyte function despite progressive CD146 expression once passaged. Thus, cell culture conditions appear to influence expression of this and other reported pericyte markers significantly without correlation to function. The newly developed assays, therefore, promise to close a gap in the in vitro identification of pericytes via function. Indeed, our functional data suggest that pericytes represent a subpopulation of MSCs in bm with a specialized role in vascular biology. However, these functions are not inherent to all MSCs.

Inwards Buildup of Concentric Polymer Layers: A Method for Biomolecule Encapsulation and Microcapsule Encoding†

Encoding by encapsulation: A polymeric shell fabrication approach combines biomolecule encapsulation with encoding. Striated polymeric shells, fabricated through an inwards diffusion of poly(allyla ...

Predictive value of the velocity of collateral filling in patients with acute ischemic stroke

The velocity of collateral filling can be assessed in dynamic time-resolved computed tomography (CT) angiographies and may predict initial CT perfusion (CTP) and follow-up lesion size. We included all patients with an M1± internal carotid artery (ICA) occlusion and follow-up imaging from an existing cohort of 1791 consecutive patients who underwent multimodal CT for suspected stroke. The velocity of collateral filling was quantified using the delay of time-to-peak (TTP) enhancement of the M2 segment distal to the occlusion. Cerebral blood volume (CBV) and mean transit time (MTT)-CBV mismatch were assessed in initial CTP. Follow-up lesion size was assessed by magnetic resonance imaging (MRI) or non-enhanced CT (NECT). Multivariate analyses were performed to adjust for extent of collateralization and type of treatment. Our study comprised 116 patients. Multivariate analysis showed a short collateral blood flow delay to be an independent predictor of a small CBV lesion (P<0.001) and a large relative mismatch (P<0.001) on initial CTP, of a small follow-up lesion (P<0.001), and of a small difference between initial CBV and follow-up lesion size (P=0.024). Other independent predictors of a small lesion on follow-up were a high morphologic collateral grade (P=0.001), lack of an additional ICA occlusion (P=0.009), and intravenous thrombolysis (P=0.022). Fast filling of collaterals predicts initial CTP and follow-up lesion size and is independent of extent of collateralization.

Cost-Effectiveness of Endovascular Stroke Therapy: A Patient Subgroup Analysis From a US Healthcare Perspective

Background and Purpose— Endovascular therapy in addition to standard care (EVT+SC) has been demonstrated to be more effective than SC in acute ischemic large vessel occlusion stroke. Our aim was to determine the cost-effectiveness of EVT+SC depending on patients’ initial National Institutes of Health Stroke Scale (NIHSS) score, time from symptom onset, Alberta Stroke Program Early CT Score (ASPECTS), and occlusion location. Methods— A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALYs) associated with both strategies applied in a US setting. Model input parameters were obtained from the literature, including recently pooled outcome data of 5 randomized controlled trials (ESCAPE [Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke], EXTEND-IA [Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial], MR CLEAN [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands], REVASCAT [Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within 8 Hours of Symptom Onset], and SWIFT PRIME [Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment]). Probabilistic sensitivity analysis was performed to estimate uncertainty of the model results. Net monetary benefits, incremental costs, incremental effectiveness, and incremental cost-effectiveness ratios were derived from the probabilistic sensitivity analysis. The willingness-to-pay was set to

Assembly of biomacromolecule loaded polyelectrolyte multilayer capsules by using water soluble sacrificial templates

50 000/QALY. Results— Overall, EVT+SC was cost-effective compared with SC (incremental cost:

Strategies of Collateral Blood Flow Assessment in Ischemic Stroke: Prediction of the Follow-Up Infarct Volume in Conventional and Dynamic CTA

4938, incremental effectiveness: 1.59 QALYs, and incremental cost-effectiveness ratio:

Self-Assembly of Polyamines as a Facile Approach to Fabricate Permeability Tunable Polymeric Shells for Biomolecular Encapsulation

3110/QALY) in 100% of simulations. In all patient subgroups, EVT+SC led to gained QALYs (range: 0.47–2.12), and mean incremental cost-effectiveness ratios were considered cost-effective. However, subgroups with ASPECTS ⩽5 or with M2 occlusions showed considerably higher incremental cost-effectiveness ratios (

Utilizing microfluidics to synthesize polyethylene glycol microbeads for Förster resonance energy transfer based glucose sensing

14 273/QALY and

Surface‐Bound Microenclosures for Biomolecules

28 812/QALY, respectively) and only reached suboptimal acceptability in the probabilistic sensitivity analysis (75.5% and 59.4%, respectively). All other subgroups had acceptability rates of 90% to 100%. Conclusions— EVT+SC is cost-effective in most subgroups. In patients with ASPECTS ⩽5 or with M2 occlusions, cost-effectiveness remains uncertain based on current data.

Sourcing of an alternative pericyte-like cell type from peripheral blood in clinically relevant numbers for therapeutic angiogenic applications.

In the quest for greater control over biomacromolecular loading and higher encapsulation efficiencies for biomacromolecule loaded microcapsules we devised a novel approach employing water soluble sacrificial templates. In traditional layer by layer (LbL) methods, aqueous solutions of polyelectrolyte salts in combination with water insoluble sacrificial template materials are used to prepare polyelectrolyte microcapsules that can be loaded with biomacromolecules. Here, we replaced the aqueous phase with pure aliphatic alcohols (Reversed-Phase) to greatly enhance the retention of biomacromolecular cargo close to 100% during microcapsule preparation in this Reverse-Phase Layer by Layer (RP-LbL) process. Formation of stable multilayered polyelectrolyte membranes onto water soluble template materials by sequential deposition of polystyrenesulfonic acid (PSS) and polyallylamine (PA) from pure 1-butanol is reported for the first time. The challenge to exert control over the biomacromolecule concentration within the template material and the resulting microcapsules was addressed by sacrificial template materials. Sacrificial template materials are water soluble and comprise of biomacromolecules embedded into a matrix of small molecular weight molecules such as glucose. Control over the concentration of biomacromolecules in the template material and microcapsules is conveniently exerted by adjusting weight ratios of bimacromolecules to sacrificial template material. This approach is envisioned to be applied alternatively to traditional polyelectrolyte microcapsule preparation techniques in cases where minute losses of expensive biomacromolecules are unfavorable or when accurate control over biomacromolecule concentration is important.