Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

Stem cell-based regenerative opportunities for the liver: State of the art and beyond

The existing mismatch between the great demand for liver transplants and the number of available donor organs highlights the urgent need for alternative therapeutic strategies in patients with acute or chronic liver failure. The rapidly growing knowledge on stem cell biology and the intrinsic repair processes of the liver has opened new avenues for using stem cells as a cell therapy platform in regenerative medicine for hepatic diseases. An impressive number of cell types have been investigated as sources of liver regeneration: adult and fetal liver hepatocytes,intrahepatic stem cell populations,annex stem cells,adult bone marrow-derived hematopoietic stem cells,endothelial progenitor cells,mesenchymal stromal cells,embryonic stem cells,and induced pluripotent stem cells. All these highly different cell types,used either as cell suspensions or,in combination with biomaterials as implantable liver tissue constructs,have generated great promise for liver regeneration. However,fundamental questions still need to be addressed and critical hurdles to be overcome before liver cell therapy emerges. In this review,we summarize the state-of-the-art in the field of stem cell-based therapies for the liver along with existing challenges and future perspectives towards a successful liver cell therapy that will ultimately deliver its demanding goals.

Magnetic resonance evaluation of human mesenchymal stem cells in corpus cavernosa of rats and rabbits

Aim： To investigate whether the biological process of superparamagnetic iron oxide （SPIO）-labeled human mesenchymal stem cells （hMSCs） may be monitored non-invasively by using in vivo magnetic resonance （MR） imaging with conventional 1.5-T system examinations in corpus cavernosa of rats and rabbits. Methods： The labeling efficiency and viability of SP10-labeled hMSCs were examined with Prussian blue and Tripan blue, respectively. After SPIO-labeled hMSCs were transplanted to the corpus cavernosa of rats and rabbits, serial T2-weighted MR images were taken and histological examinations were carried out over a 4-week period. Results： hMSCs loaded with SPIO compared to unlabeled cells had a similar viability. For SPIO-labeled hMSCs more than lx 105 concentration in vitro, MR images showed a decrease in signal intensity. MR signal intensity at the areas of SPIO-labeled hMSCs in the rat and rabbit corpus cavernosa decreased and was confined locally. After injection of SPIO-labeled hMSCs into the corpus cavernosum, MR imaging demonstrated that hMSCs could be seen for at least 12 weeks after injection. The presence of iron was confirmed with Prussian blue staining in histological sections. Conclusion： SP10-labeled hMSCs in corpus cavernosa of rats and rabbits can be evaluated non-invasively by molecular MR imaging. Our findings suggest that MR imaging has the ability to test the long-term therapeutic potential of hMSCs in animals in the setting of erectile dysfunction.

Stem cell transplantation for treating Duchenne muscular dystrophy A Web of Science-based literature analysis

OBJECTIVE： To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy indexed in Web of Science; （b） original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and （c） publication between 2002 and 2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） documents that were not published in the public domain; and （c） corrected papers. MAIN OUTCOME MEASURES： （1）Annual publication output; （2） distribution according to subject areas; （3） distribution according to journals; （4） distribution according to country; （5） distribution according to institution; （6） distribution according to institution in China; （7） distribution according to institution that cooperated with Chinese institutions; （8） top-cited articles from 2002 to 2006; （9） top-cited articles from 2007 to 2011. RESULTS： A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation for treating Duchenne muscular dystrophy. CONCLUSION： The publications on stem cell transplantation for treating Duchenne muscular dystrophy were relatively few. It also needs more research to confirm that stem cell therapy is a reliable treatment for Duchenne muscular dystrophy.

Mononuclear cells from the cord blood and granulocytecolony stimulating factor-mobilized peripheral blood:is there a potential for treatment of cerebral palsy?

To investigate a possible therapeutic mechanism of cell therapy in the field of cerebral palsy using granulocyte-colony stimulating factor（G-CSF）-mobilized peripheral blood mononuclear cells（m PBMCs）,we compared the expression of inflammatory cytokines and neurotrophic factors in PBMCs and m PBMCs from children with cerebral palsy to those from healthy adult donors and to cord blood mononuclear cells donated from healthy newborns.No significant differences in expression of neurotrophic factors were found between PBMCs and m PBMCs.However,in cerebral palsy children,the expression of interleukin-6 was significantly increased in m PBMCs as compared to PBMCs,and the expression of interleukin-3 was significantly decreased in m PBMCs as compared to PBMCs.In healthy adults,the expression levels of both interleukin-1βand interleukin-6 were significantly increased in m PBMCs as compared to PBMCs.The expression of brain-derived neurotrophic factors in m PBMC from cerebral palsy children was significantly higher than that in the cord blood or m PBMCs from healthy adults.The expression of G-CSF in m PBMCs from cerebral palsy children was comparable to that in the cord blood but significantly higher than that in m PBMCs from healthy adults.Lower expression of pro-inflammatory cytokines（interleukin-1β,interleukin-3,and-6）and higher expression of anti-inflammatory cytokines（interleukin-8 and interleukin-9）were observed from the cord blood and m PBMCs from cerebral palsy children rather than from healthy adults.These findings indicate that m PBMCs from cerebral palsy and cord blood mononuclear cells from healthy newborns have the potential to become seed cells for treatment of cerebral palsy.

Fentanyl inhibits glucose-stimulated insulin release from β-cells in rat pancreatic islets

AIM： TO explore the effects of fentanyl on insulin release from freshly isolated rat pancreatic islets in static culture. METHODS： Islets were isolated from the pancreas of mature Sprague Dawley rats by common bile duct intraductal collagenase V digestion and were purified by discontinuous Ficoll density gradient centrifugation. The islets were divided into four groups according to the fentanyl concentration： control group （0 ng/mL）, group I （0.3 ng/mL）, group I （3.0 ng/mL）, and group III （30 ng/mL）. In each group, the islets were co-cultured for 48 h with drugs under static conditions with fentanyl alone, fentanyl ＋ 0.1 μg/mL naloxone or fentanyl ＋ 1.0 μg/mL naloxone. Cell viability was assessed by the MTT assay. Insulin release in response to low and high concentrations （2.8 mmol/L and 16.7 mmol/L, respectively） of glucose was investigated and electron microscopy morphological assessment was performed. RESULTS： Low- and high-glucose-stimulated insulin release in the control group was significantly higher than in groups I and II （62.33 ± 9.67 μIU vs 47.75 ± 8.47 μIU, 39.67 ± 6.18 μIU and 125.5 ± 22.04 μIU vs 96.17 ± 14.17 μIU, 75.17 ± 13.57 μIU, respectively, P 〈 0.01） and was lowest in group III （P 〈 0.01）. After adding 1 μg/mL naloxone, insulin release in groups II and II was not different from the control group. Electron microscopy studies showed that the islets were damaged by 30 ng/ml fentanyl. CONCLUSION： Fentanyl inhibited glucose-stimulated insulin release from rat islets, which could be prevented by naloxone. Higher concentrations of fentanyl significantly damaged β-cells of rat islets.

Motor neuron replacement therapy for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a motor neuron degenerative disease that is also known as Lou Gehrig’s disease in the United States,Charcot’s disease in France,and motor neuron disease in the UK.The loss of motor neurons causes muscle wasting,paralysis,and eventually death,which is commonly related to respiratory failure,within 3-5 years after onset of the disease.Although there are a limited number of drugs approved for amyotrophic lateral sclerosis,they have had little success at treating the associated symptoms,and they cannot reverse the course of motor neuron degeneration.Thus,there is still a lack of effective treatment for this debilitating neurodegenerative disorder.Stem cell therapy for amyotrophic lateral sclerosis is a very attractive strategy for both basic and clinical researchers,particularly as transplanted stem cells and stem cell-derived neural progenitor/precursor cells can protect endogenous motor neurons and directly replace the lost or dying motor neurons.Stem cell therapies may also be able to re-establish the motor control of voluntary muscles.Here,we review the recent progress in the use of neural stem cells and neural progenitor cells for the treatment of amyotrophic lateral sclerosis.We focus on MN progenitor cells derived from fetal central nervous system tissue,embryonic stem cells,and induced pluripotent stem cells.In our recent studies,we found that transplanted human induced pluripotent stem cell-derived motor neuron progenitors survive well,differentiate into motor neurons,and extend axons into the host white matter,not only in the rostrocaudal direction,but also along motor axon tracts towards the ventral roots in the immunodeficient rat spinal cord.Furthermore,the significant motor axonal extension after neural progenitor cell transplantation in amyotrophic lateral sclerosis models demonstrates that motor neuron replacement therapy could be a promising therapeutic strategy for amyotrophic lateral sclerosis,particularly as a variety of stem cell derivatives,including induced pluripotent stem cells,are being considered for clinical trials for various diseases.

WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Mesenchymal stem cells in treating autism:Novel insights

Autism spectrum disorders(ASDs)are complex neurodevelopmental disorders characterized by dysfunctions in social interactions,abnormal to absent verbal communication,restricted interests,and repetitive stereotypic verbal and non-verbal behaviors,influencing the ability to relate to and communicate.The core symptoms of ASDs concern the cognitive,emotional,and neurobehavioural domains.The prevalence of autism appears to be increasing at an alarming rate,yet there is a lack of effective and definitive pharmacological options.This has created an increased sense of urgency,and the need to identify novel therapies.Given the growing awareness of immune dysregulation in a significant portion of the autistic population,cell therapies have been proposed and applied to ASDs.In particular,mesenchymal stem cells(MSCs)possess the immunological properties which make them promising candidates in regenerative medicine.MSC therapy may be applicable to several diseases associated with inflammation and tissue damage,where subsequent regeneration and repair is necessary.MSCs could exert a positive effect in ASDs through the following mechanisms:stimulation of repair in the damaged tissue,e.g.,inflammatory bowel disease;synthesizing and releasing anti-inflammatory cytokines and survival-promoting growth factors;integrating into existing neural and synaptic network,and restoring plasticity.The paracrine mechanisms of MSCs show interesting potential in ASD treatment.Promising and impressive results have been reported from the few clinical studies published to date,although the exact mechanisms of action of MSCs in ASDs to restore functions are still largely unknown.The potential role of MSCs in mediating ASD recovery is discussed in light of the newest findings from recent clinical studies.

Transplantation of mobilized peripheral blood mononuclear cells for peripheral arterial occlusive disease of the lower extremity

Objectives To assess the clinical efficacy,safety,and feasibility of autologous transplantation of mobilized peripheral blood mononuclear cells(PBMNCs)for patients with peripheral arterial occlusive disease(PAOD)of the lower extremity.Methods A total of 152 patients with PAOD of the lower extremity were enrolled into this non-controlled observational study from November 2003 to March 2006.All patients received subcutaneous injections of recombinant human granulocyte colony-stimulating factor(G-CSF,450-600μg/day)for 5 days in order to mobilize stem/progenitor cells;their PBMNCs were collected and transplanted by multiple intramuscular injections into ischemic limbs.Patients were followed up for at least 12 weeks.Results At 12 weeks,primary manifestations,including lower limb pain and coldness,were significantly improved in 137(90.1%)of the patients;limb ulcers improved or healed in 46(86.8%)of the 53 patients,while 25 of the 48(47.9%)patients with limb gangrene remained steady or improved.Ankle-brachial index(ABI)improved in 33(22%)of the cases,and TcPO_(2) increased in 45(30%)of the cases.Angiography before treatment,and at 12 weeks after treatment,was performed in 10 of the patients and showed formation of new collateral vessels.No severe adverse effects or complications specifically related to cell transplantation were observed.Conclusion Autologous transplantation of G-CSF-mobilized PBMNCs might be a safe and effective treatment for lower limb ischemic disorder.

Management of adult Langerhans cell histiocytosis based on the characteristic clinical features

To find out the most appropriate management,clinical features of 18 cases of adult multisystem langerhans cell histiocytosis(LCH) have been analyzed. The patients comprising of 9 males and 9 females were median age of 36 years,ranging from 18-53 years at diagnosis. Regarding the initial symptoms,7 patients(2 males and 5 females) showed central diabetes insipidus(CDI) and other endocrine symptoms with thickened pituitary stalk or a mass at the hypothalamic region. Additional 2 patients initiated the disease with CDI with no immediate diagnosis. In the remaining patients,the diseasebegun with single(n = 3) or multiple(n = 1) spinal bone lesion(s) in 4 patients(all males),with multiple bone lesions in 3 patients(1 male and 2 females),with single skull lesion in one female patient and with ambiguous symptoms including hypothyroidism in the remaining one male patient. We also recognized the correlation between pregnancy/childbirth and LCH in 4 patients. In terms of treatment,9 patients received systemic immuno-chemotherapy alone,of which the majority received vinblastine-based chemotherapy while 4 received 2-chlorodeoxyadenosine. Five had a combination of immuno-chemotherapy with surgical resection or radiotherapy,2 had immunotherapy alone,2 had surgical resection followed by observation alone to date. Three patients received hematopoietic stem cell transplantation after extensive chemotherapy. In terms of outcome,15 patients are alive(9 with active disease,6 without active disease),with a median of 66 mo(range 17-166 mo),two died of disease while the remaining 1 lost to follow-up. Based on these results,we think that early diagnosis and rapid introduction of appropriate treatment are essential,in order to overcome the problems relevant to adult LCH.

Cell therapy for macular degeneration—first phase Ⅰ/Ⅱ pluripotent stem cell-based clinical trial shows promise

Embryonic stem（ES）cells,a type of pluripotent stem cells（PSCs）that are derived from the inner cell mass of blastocysts,have been discovered for more than three decades[1].Given the almost infinite self-renewal capacity and the potential to differentiate into any specific cell type in an individual,ES cells and PSCs have brought hope for the treatment of many unmet diseases.However,the advantages of PSCs-the highly proliferative and plastic capacities,also give rise to concerns regarding the development of tumors.

Prediction of hepatic inflammation in chronic hepatitis B patients with a random forest-backward feature elimination algorithm

BACKGROUND Persistent liver inflammatory damage is the main risk factor for developing liver fibrosis,cirrhosis,and even hepatocellular carcinoma in chronic hepatitis B(CHB)patients.Thus,accurate prediction of the degree of liver inflammation is a high priority and a growing medical need.AIM To build an effective and robust non-invasive model for predicting hepatitis Brelated hepatic inflammation.METHODS A total of 650 treatment-naïve CHB(402 HBeAg-positive and 248 HBeAgnegative)patients who underwent liver biopsy were enrolled in this study.Histological inflammation grading was assessed by the Ishak scoring system.Serum quantitative hepatitis B core antibody(qAnti-HBc)levels and 21 immunerelated inflammatory factors were measured quantitatively using a chemiluminescent microparticle immunoassay.A backward feature elimination(BFE)algorithm utilizing random forest(RF)was used to select optional features and construct a combined model.The diagnostic abilities of the model or variables were evaluated based on the estimated area under the receiver operating characteristics curve(AUROC)and compared using the DeLong test.RESULTS Four features were selected to predict moderate-to-severe inflammation in CHB patients using the RF-BFE method.These predictive features included qAnti-HBc,ALT,AST,and CXCL11.Spearman’s correlation analysis indicated that serum qAnti-HBc,ALT,AST,and CXCL11 levels were positively correlated with the histology activity index(HAI)score.These selected features were incorporated into the model to establish a novel model named I-3A index.The AUROC[0.822;95%confidence interval(CI):0.790-0.851]of the I-3A index was significantly increased compared with qAnti-HBc alone(0.760,95%CI:0.724-0.792,P<0.0001)in all CHB patients.The use of an I-3A index cutoff value of 0.41 produced a sensitivity of 69.17%,specificity of 81.44%,and accuracy of 73.8%.Additionally,the I-3A index showed significantly improved diagnostic performance for predicting moderate-to-severe inflammation in HBeAg-positive and HBeAgnegative CHB patients(0.829,95%CI:0.789-0.865 and 0.810,95%CI:0.755-0.857,respectively).CONCLUSION The selected features of the I-3A index constructed using the RF-BFE algorithm can effectively predict moderate-to-severe liver inflammation in CHB patients.

China enters CAR-T cell therapy era

The emerging individualized and living-cell-based genetic engineering chimeric antigen receptor T(CAR-T)therapy demonstrates great curative effects in some hematological tumor treatments,thus it is turning out to be a star immunotherapy method of the world.1 Recently,the China NationalMedical Products Administration(NMPA)approved launching applications of two CAR-T cell cancer products,Axicabtagene Ciloleucel(FKC876)and Relmacabtagene Autoleucel(Carteyva),which marked the beginning of the of CAR-T cell therapy era in China(Figure 1).

Salvianolic Acid B Down-regulates Matrix Metalloproteinase-9 Activity and Expression in Tumor Necrosis Factor-α-induced Human Coronary Artery Endothelial Cells

Background：Salvianolic acid B （Sal B） is a bioactive water-soluble compound of Salviae miltiorrhizae,a traditional herbal medicine that has been used clinically tor the treatment of cardiovascular diseases.This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 （MMP-9） and on the underlying mechanisms in tumor necrosis factor-α （TNF-α）-activated human coronary artery endothelial cells （HCAECs）,a cell model of Kawasaki disease.Methods：HCAECs were pretreated with 1 l0 μmol/L of Sal B,and then stimulated by TNF-α at different time points.The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay,respectively.Nuclear factor-κB （NF-κB） activation was detected with immunofluorescence,electrophoretic mobility shift assay,and Western blot assay.Protein expression levels of mitogen-activated protein kinase （c-Jun N-terminal kinase [JNK],extra-cellular signal-regulated kinase [ERK],and p38） were determined by Western blot assay.Results：After HCAECs were exposed to TNF-α,1-10 μtmol/L Sal B significantly inhibited TNF-α-induced MMP-9 expression and activity.Furthermore,Sal B significantly decreased IκBα phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α for 30 min.In addition,Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α for 10 min.Conclusions：The data suggested that Sal B suppressed TNF-α-induced MMP-9 expression and activity by blocking the activation of NF-κB,JNK,and ERK1/2 signaling pathways.

Biological properties of neural progenitor cells isolated from the hippocampus of adult cynomolgus monkeys

Background The existence of neurogenesis in the hippocampus of adult nonhuman primates has been confirmed in recent years, however, the biological properties of adult neural stem cells or neural progenitor cells （NPCs） from this region remain to be extensively explored. The present work was to investigate on the expansion of NSCs/NPCs from the hippocampus of adult cynomolgus monkeys and the examination of their characteristics in vitro. Methods NPCs isolated from the hippocampus of adult cynomolgus monkeys were expanded in vitro in serum-free media containing growth factors, and were then allowed to differentiate by removing mitotic factors. The expansion capacity of NPCs and their differentiation potential were assayed by immunohistochemical and immunocytochemical analysis. Results During primary culture, NPCs underwent cell division, proliferation and aggregation to form neurospheres that were growing in suspension. Without mitotic stimulation, most neurospheres adhered to the culture dish and started to differentiate. Eventually, nearly 12% of the differentiated cells expressed neuron specific marker-β Ⅲ-tubulin （Tuj1） and 84% expressed astrocyte specific marker-fibrillary acidic protein （GFAP）. In addition, the expression of a neural stem cell marker, nestin, was found both in NPCs and in the subgranular zone of adult monkey hippocampus, where NPCs were originally derived. Conclusions NPCs from the hippocampus of adult cynomolgus monkeys can be expanded to some extent in vitro and are capable of differentiating into neurons and astrocytes. Further experiments to promote the in vitro proliferation capacity of NPCs will be required before adult NPCs can be used as a useful cell model for studying adult neurogenesis and cell replacement therapy using adult stem cells.

Labeling of cynomolgus monkey bone marrow-derived mesenchymal stem cells for cell tracking by multimodality imaging

Recently,transplantation of allogeneic and autologous cells has been used for regenerative medicine.A critical issue is monitoring migration and homing of transplanted cells,as well as engraftment efficiency and functional capability in vivo.Monitoring of superparamagnetic iron oxide(SPIO) particles by magnetic resonance imaging(MRI) has been used in animal models and clinical settings to track labeled cells.A major limitation of MRI is that the signals do not show biological characteristics of transplanted cells in vivo.Bone marrow mesenchymal stem cells(MSCs) have been extensively investigated for their various therapeutic properties,and exhibit the potential to differentiate into cells of diverse lineages.In this study,cynomolgus monkey MSCs(cMSCs) were labeled with Molday ION Rhodamine-BTM(MIRB),a new SPIO agent,to investigate and characterize the biophysical and MRI properties of labeled cMSCs in vitro and in vivo.The results indicate that MIRB is biocompatible and useful for cMSCs labeling and cell tracking by multimodality imaging.Our method is helpful for detection of transplanted stem cells in vivo,which is required for understanding mechanisms of cell therapy.

Comparative characterization of mesenchymal stem cells from different age groups of cynomolgus monkeys

Bone marrow mesenchymal stem cells(BM-MSCs) are a potential tool for cell therapy and tissue engineering.In this study,we carried on a comparative study of the characteristics of MSCs from different age cynomolgus monkeys.A variety of factors,including donor age,must be considered before further applications,and various tests should be used to properly assess MSCs before the clinical application,especially when a prolonged culture and ex vivo expansion is necessary.

Accelerated generation of oligodendrocyte progenitor cells from human induced pluripotent stem cells by forced expression of Sox10 and Olig2

Oligodendrocyte progenitor cells(OPCs) hold great promise for treatment of dysmyelinating disorders, such as multiple sclerosis and cerebral palsy. Recent studies on generation of human OPCs mainly use human embryonic stem cells(hESCs) or neural stem cells(NSCs) as starter cell sources for the differentiation process. However, NSCs are restricted in availability and the present method for generation of oligodendrocytes(OLs) from ESCs often requires a lengthy period of time. Here, we demonstrated a protocol to efficiently derive OPCs from human induced pluripotent stem cells(hiPSCs) by forced expression of two transcription factors(2TFs), Sox10 and Olig2. With this method, PDGFRα+ OPCs can be obtained in 14 days and O4^+ OPCs in 56 days.Furthermore, OPCs may be able to differentiate to mature OLs that could ensheath axons when co-cultured with rat cortical neurons. The results have implications in the development of autologous cell therapies.

Harnessing novel engineered feeder cells expressing activating molecules for optimal expansion of NK cells with potent antitumor activity

Natural killer(NK)cells play an important role in the antitumor immune response as the major cytotoxic lymphocytes in the innate immune system.NK cells without any genetic modifications have been used for both autologous and allogeneic therapies.Moreover,many reports have suggested that allogeneic NK cells can reduce the recurrence of disease and improve survival through a graft-versus-leukemia effect without GVHD[1,2].