Citations

Study Design Human bone marrow stem cells (hBMSCs) and human adipose-derived stem cells (hADSCs) have demonstrated the capability to regenerate bone once they have differentiated into osteoblasts. Objective This systematic review aimed to evaluate the in vitro osteogenic differentiation potential of these cells when seeded in a poly (lactic- co-glycolic) acid (PLGA) scaffold. Methods A literature search of 4 databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted in January 2021 for studies evaluating the osteogenic differentiation potential of hBMSCs and hADSCs seeded in a PLGA scaffold. Only in vitro models were included. Studies in languages other than English were excluded. Results A total of 257 studies were identified after the removal of duplicates. Seven articles fulfilled our inclusion and exclusion criteria. Four of these reviews used hADSCs and three used hBMSCs in the scaffold. Upregulation in osteogenic gene expression was seen in all the cells seeded in a 3-dimensional scaffold compared with 2-dimensional films. High angiogenic gene expression was found in hADSCs. Addition of inorganic material to the scaffold material affected cell performance. Conclusions Viability, proliferation, and differentiation of cells strongly depend on the environment where they grow. There are several factors that can enhance the differentiation capacity of stem cells. A PLGA scaffold proved to be a biocompatible material capable of boosting the osteogenic differentiation potential and mineralization capacity in hBMSCs and hADSCs.

Abstract Background Extracellular vesicles (EVs) have gained interest in the field of regenerative and transfusion medicine. Specifically, current Good Manufacturing Practice (cGMP)‐grade EVs produced by mesenchymal stromal cells (MSCs) are an intriguing option for cell‐free therapeutics. With the development of cGMP‐grade EV products, a simple and reliable method for batch‐to‐batch consistency is needed. Study Design and Methods The objective of this study was to validate a method to semiquantitatively assess the batch‐to‐batch consistency of isolated EVs. A multiplex bead‐based flow cytometric assay containing 37 surface markers and 2 assay control antibody‐coated capture beads was validated. Detection limits ( n = 10 buffer samples), repeatability ( n = 9 EV samples), and intra‐observer reproducibility over 2 days ( n = 10 EV batches) were assessed. A Spearman correlation matrix was used to evaluate the batch‐to‐batch consistency of independently isolated EV products ( n = 37 surface markers). Batches with a Spearman correlation coefficient ≥0.9 and p < 0.05 were considered statistically indistinguishable from previous batches. Results This assay demonstrated robust repeatability as well as intra‐ and inter‐assay reproducibility. In‐house batches of EVs were significantly correlated (r ≥ 0.90; p ≤ 1×10 −14 ). Compared with buffer, EV batches had correlation coefficients near zero (r ≤ −0.10; p ≥ 0.12). Commercially sourced EVs significantly correlated with in‐house EV batches, but fell below the 90% correlation cutoff (r ≤ 0.71; p ≤ 0.0004). Discussion This time‐efficient and technically simple assay offers a robust method of quality control for assessing the batch‐to‐batch reproducibility of cGMP‐grade EV products.

Abstract Background We have previously shown bone marrow-derived mesenchymal stem cells (MSCs) may shift immune responses toward anti-inflammatory pathways and stabilize the course of obstructive chronic lung allograft syndrome (o-CLAD) after lung transplantation. In this study, we measured the response of lower dose infusions. Methods We infused low-dose MSCs intravenously in 13 patients who had developed moderate-to-severe o-CLAD. Three had previously received an infusion of MSCs from a different donor and were re-dosed at 1 × 106 MSC/kg, while 5 received a first dose at 1 × 106 MSC/kg and five received an even lower dose at 0.5 × 106 MSC/kg. We recorded pulmonary function tests before and after infusion, and patients were followed clinically for 12 months. Results Infusions were well tolerated, and no significant adverse events were recorded in the first 30 days. There was significant decline (mean ± SD) in forced vital capacity (FVC) (3.49 ± 1.03 vs 3.18 ± 0.94 L, P = .03) and forced expiratory volume in 1 second (FEV1) (2.28 ± 0.86 vs 1.77 ± 0.49 L, P = .04) over the year preceding infusion. FVC (3.18 ± 0.94 vs 3.46 ± 0.99 L, P = .53) and FEV1 was not significantly changed (1.77 ± 0.49 vs 1.88 ± 0.75, P = .72) when comparing values immediately prior to infusion to those obtained 1 year after infusion, indicating a possible stabilizing effect on lung function decline due to o-CLAD. Conclusion Intravenous infusions of bone marrow-derived MSCs are well tolerated in lung transplant recipients with moderate-to-severe CLAD. Low-dose MSCs appear to slow progression of CLAD in some patients.

Patients with delayed and normal gastric emptying (GE) had similar symptom profiles during gastric emptying scintigraphy (GES). Idiopathic patients with symptoms of gastroparesis had less gastric retention by GES; but more symptoms after GES meal and after water load satiety test (WLST) compared with diabetic patients. In patients with symptoms of gastroparesis, symptoms after WLST increased with decreasing water consumption. Early satiety and loss of appetite were associated with decreased water consumption during WLST. Thus, impaired accommodation and perhaps visceral hypersensitivity are important in explaining postprandial symptoms in gastroparesis.

AbstractDrug‐resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE. Medline, Ovid EMBASE, Scopus, and the Cochrane Databases were searched electronically from their dates of inception to November 2021 using the following keywords: ((“mesenchymal”) AND (“stem cell”)) AND ((“epilepsy”) OR (“convulsion”) OR (“seizures”)). This review followed Preferred Reporting Items for Systemic Reviews and Meta‐Analyses (PRISMA) guidelines. The initial query identified 488 studies representing 323 unique manuscripts. After application of selection criteria, 15 studies were included in this systematic review; 11 were preclinical studies and 4 were clinical studies. All preclinical studies were performed in rodents and all clinical studies were phase 1 trials. Thus far, therapy with MSCs appears to be safe for use in humans, as no severe adverse events related directly to the therapy were reported. Furthermore, MSC therapy appears to provide a statistically significant clinical benefit by reducing the seizure burden of patients, reducing the electrophysiological biomarkers of epilepsy, and improving their comorbidities, such as depression and anxiety. In addition, animal studies reveal that the therapy exerts its effect by reducing aberrant mossy fiber sprouting (reduce excitatory pathways) and increasing γ‐aminobutyric acid (GABA)ergic interneurons (increase inhibitory pathways). Both preclinical and clinical studies have shown MSC therapy to be safe and preliminary effective, thus warranting further studies to investigate its therapeutic potential.

Background: Cerebral microbleeds (CMB) incidentally found during an MRI evaluation of ischemic stroke present a therapeutic dilemma. Case control studies suggest a relationship of cerebral microbleeds and intracerebral hemorrhage. Limited prospective studies of patients with ischemic stroke show variability in whether CMB hemorrhage rates are greater than recurrent ischemic stroke rates. Our aim was to determine the prevalence and characteristics of CMB in patients with atrial fibrillation presenting with stroke and secondly what the rate of prospective intracerebral hemorrhage (ICH) was in those same patients. Methods: Consecutive patients admitted with atrial fibrillation and stroke were identified in our institution’s Get with the Guideline database between 2008-2009. Data from the incident hospitalization included: demographic information, use of antithrombotic and/or anticoagulation, and cerebrovascular risk factors. Radiologic imaging was reviewed to determine if a GRE or SWI sequence was included and record the number and location of CMB. Follow up information was obtained by chart review and written survey or phone call. Death certificates were obtained where applicable. Results: 240 patients were identified, 128 of whom had a CT only and 112 who had an MRI. Of those with an MRI, 76 had GRE or SWI sequences. Twenty-one of 76 patients with a GRE or SWI sequence had a CMB (prevalence: 27.6%). One patient in the CMB (+) group had a prospective hemorrhage during an average follow up of 3 years (rate: 0.33 ICH per patient year of follow up). No patients in the CMB negative group had an ICH. Conclusions: Our study demonstrates the prevalence of cerebral microbleeds is much higher than the actual prospective hemorrhage rate. The prospective hemorrhage rate is low and consistent with findings from large, randomized anticoagulation studies in patients with atrial fibrillation.