Cell medicine最新文献

Bronchopulmonary dysplasia (BPD), a disease affecting extremely premature infants, results from the disruption of normal pulmonary vascular and alveolar growth. Currently, there is no specific effective treatment. We report a case of a 10-mo-old female infant with BPD, who was admitted because of adenovirus pneumonia and acute respiratory distress syndrome (ARDS) with prolonged venovenous and arteriovenous extracorporeal membrane oxygenation (ECMO) support (total 125 d). The respiratory condition dramatically improved, and ECMO was removed 25 d after intratracheal delivery of maternal bone marrow-derived mesenchymal stem cells (BM-MSCs). Short tandem repeat examinations revealed that there was no maternal cells in the bronchial wash fluid. To our knowledge, this is the first human report of BM-MSC therapy reversal of the course of BPD superimposed with ARDS. We also suggest that BM-MSC therapy may not only be effective in the newborn stage but also works in infants and children with BPD.

During development, stem cells generate all of the differentiated cells that populate our tissues and organs. Stem cells are also responsible for tissue turnover and repair in adults, and as such, they hold tremendous promise for regenerative therapy. Aging, however, impairs the function of stem cells and is thus a significant roadblock to using stem cells for therapy. Paradoxically, the patients who would benefit the most from regenerative therapies are usually advanced in age. The use of stem cells from young donors or the rejuvenation of aged patient-derived stem cells may represent part of a solution. Nonetheless, the transplantation success of young or rejuvenated stem cells in aged patients is still problematic, since stem cell function is greatly influenced by extrinsic factors that become unsupportive with age. This article briefly reviews how aging impairs stem cell function, and how this has an impact on the use of stem cells for therapy.

Across scientific disciplines, 3-D organoid culture systems offer platforms to integrate basic research findings with clinical care. The National Eye Institute mounted a $1.1 million 3-D Retina Organoid Challenge. Organoids developed through the Challenge will be valuable resources for drug screening, disease modeling, and precision and regenerative medicine.

Purification of pancreatic islets is an important step in islet isolation for islet transplantation. In this study, to investigate how a solution composed mainly of Na-lactobionate and histidine (HL) influences the purification of islets, iodixanol was added to a purified solution for porcine islet isolation. A solution (IU) made by adding iodixanol to University of Wisconsin solution and a solution (IHL) made by adding iodixanol to HL solution were used to evaluate the islet isolation performance. We noted no significant differences between the two purification methods with regard to the islet yield, survival rate or purity, score, or stimulation index. These results show that IHL solution is as useful as IU solution for islet purification.

Safety concerns over cell-derived pharmaceutical products being manufactured in supplements of fetal bovine serum (FBS) have ignited pleas to replace FBS. Herein, four newly marketed alternatives to FBS were compared: a xeno-free product called Cell-Ess®, a human platelet lysate marketed as GroPro®, and two mixtures of adult bovine serum varying in their proportions of neonatal growth factors, called Liporo® and FetalGro®. An endothelial cell line (C2BBe1) and a neuronal cell line (SHSY5Y) near confluency in media with 10% FBS were selectively scraped and taken through a 25-day step-wise algorithm to replace FBS, and another human endothelial cell line (HRA-19) was studied to replicate C2BBe1. Cells were stained, counted, and compared for viability, migration, and spheroids. The C2BBe1 and HRA-19 cell lines failed to proliferate in 10% Cell-Ess® but grew in 10% GroPro® or 10% FetalGro® reasonably well compared to reference 10% FBS. With SH-SY5Y, only FetalGro® approached FBS's efficacy. These were all inferior to 11 different branded lots of FBS (positive controls), but five days into switching just amongst the FBS brands, 4 of 11 supported less proliferation than reference FBS in endothelial HRA-19 (p < 0.004). Moreover, neurospheres were enriched in two branded lots of FBS and FetalGro® (each p < 0.004), neurospheres being an unwanted phenotype for any neuronal cell application. Because platelet-derived GroPro® stood out amongst the non-FBS growth supplements to allow proliferation without inducing spheroids, it seems the best (mindful that the cells still grew slower in it compared to FBS). While no perfect replacement was found amongst the alternatives to FBS, the algorithm for switching should be useful in future testing of new alternatives to FBS as the need arises to switch from FBS and expand pharmaceutical products with safety for human use.

Introduction: Previously we showed that a fibrin glue conduit with human mesenchymal stem cells (hMSCs) and cyclosporine A (CsA) enhanced early nerve regeneration. In this study long term effects of this conduit are investigated.

Methods: In a rat model, the sciatic nerve was repaired with fibrin conduit containing fibrin matrix, fibrin conduit containing fibrin matrix with CsA treatment and fibrin conduit containing fibrin matrix with hMSCs and CsA treatment, and also with nerve graft as control.

Results: At 12 weeks 34% of motoneurons of the control group regenerated axons through the fibrin conduit. CsA treatment alone or with hMSCs resulted in axon regeneration of 67% and 64% motoneurons respectively. The gastrocnemius muscle weight was reduced in the conduit with fibrin matrix. The treatment with CsA or CsA with hMSCs induced recovery of the muscle weight and size of fast type fibers towards the levels of the nerve graft group.

Discussion: The transplantation of hMSCs for peripheral nerve injury should be optimized to demonstrate their beneficial effects. The CsA may have its own effect on nerve regeneration.

The low efficiency of in vitro differentiation of human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (iPSCs) into insulin-producing cells is a crucial hurdle for the clinical implementation of human pluripotent stem cells (PSCs). Our previous investigation into the key factors for the differentiation of PSCs into insulin-producing cells suggested that the expression of GATA binding protein 6 (GATA6) and Gremlin 1 (GREM1) and inhibition of early growth response protein 1 (Egr1) may be important factors. In this study, we investigated the role of Egr1 in pancreas development. The transfection of small interfering RNA (siRNA) of Egr1 in the early phase induced the differentiation of iPSCs derived from fibroblasts (FiPSCs) into pancreatic endoderm and insulin-producing cells. In contrast, the downregulation of Egr1 in the late phase suppressed the differentiation of FiPSCs into pancreatic endoderm and insulin-producing cells. In addition, the overexpression of Egr1 suppressed the differentiation of iPSCs derived from pancreatic cells into pancreatic endoderm and insulin-producing cells. These data suggest that the downregulation of Egr1 in the early phase can efficiently induce the differentiation of iPSCs into insulin-producing cells.

Islet purification is one of the most important steps of islet isolation for pancreatic islet transplantation. We previously reported that a purification method using large plastic bottles effectively achieved a high yield of islets from porcine pancreas. In this study, we evaluated the methods for making a continuous density gradient and loading tissue. One method involved loading digested tissue on top of a continuous density gradient (top loading). The other method involved mixing digested tissue with low-density solution and then making a continuous gradient (mixed loading). There were no significant differences between the 2 purification methods in terms of the islet yield, rate of viability or purity, score, or in the stimulation index after purification. Furthermore, there were no marked differences in the attainability or suitability of posttransplantation normoglycemia. Our study shows the equivalency of these 2 methods of islet purification.

Stroke is an important cause of morbidity and mortality in children. Clinical presentation is diverse, and multiple risk factors have been described. The aim of this retrospective study is to describe the clinical presentation, risk factors, and the Pediatric National Institute of Health Stroke Scale (PedNIHSS) in a series of pediatric Chilean patients with the diagnosis of arterial ischemic stroke (AIS). Children diagnosed with AIS aged between 29 d and 18 y were enrolled (1989 to 2016). Clinical characteristics and risk factors were described. PedNIHSS severity score was estimated for patients older than 4 mo of age. Sixty-two patients were included, 66% were male, and the mean age of presentation was 3.5 y. Seventy-nine percent presented motor deficit, 45% seizures, and 15% consciousness impairment. Eighty-two percent had a unilateral stroke and 73% had anterior circulation territory affected. The main risk factors were arteriopathy (63%) and infection (43%). The PedNIHSS mean was 7.6, ranging between 0 and 17. In the categories in which it was possible to apply χ² test, only the acute systemic conditions category was statistically significant (P = 0.03), being higher in the group of patients younger than 3 y old. We confirmed male predominance in AIS and the most frequent presenting symptom was motor deficit. We found at least 1 risk factor in all patients with complete information. We confirmed arteriopathy as the most frequent risk factor, and acute systemic conditions were higher in patients younger than 3 y old with statistical significance (P = 0.03). The majority of patients presented mild to moderate severity in the PedNIHSS score.