Stem cell-based ischemic stroke therapy:Novel modifications and clinical challenges

Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.

Modification of Titanium Surfaces via Surface-initiated Atom Transfer Radical Polymerization to Graft PEG-RGD Polymer Brushes to Inhibit Bacterial Adhesion and Promote Osteoblast Cell Attachment

Implant-related infection is one of the key concerns in clinical medicine, so the modification of titanium to inhibit bacterial adhesion and support osteoblast cell attachment is important. In this article, two strategies were used to examine the above effects. First, modification of titanium via surface-initiated atom transfer radical polymerization（ATRP） was performed. The surface of the titanium was activated initially by a silane coupling agent. Well-defined polymer brushes of poly（ethylene glycol） methacrylate were successfully tethered on the silane-coupled titanium surface to form hydration shell to examine the anti-fouling effect. Second, functionalization of the Ti-PEG surface with RGD was performed to examine the anti-bacterial adhesion and osteoblast cell attachment ability. The chemical composition of modified titanium surfaces was characterized by X-ray photoelectron spectroscopy（XPS）. Changes in surface hydrophilicity and hydrophobicity were characterized by static water contact angle measurements. Results indicated that PEG-RGD brushes were successfully tethered on the titanium surface. And anti-bacterial adhesion ability and osteoblast cell attachment ability were confirmed by fluorescence microscopy and scanning electron microscopy. Results indicated that PEG can inhibit both bacterial adhesion and osteoblast cell attachment, while PEG-RGD brushes can not only inhibit bacterial adhesion but also promote osteoblast cell attachment.

CCaP1/CCaP2/CCaP3 interact with plasma membrane H^(+)-ATPases and promote thermoresponsive growth by regulating cell wall modification in Arabidopsis

Arabidopsis plants adapt to warm temperatures by promoting hypocotyl growth primarily through the basic helix-loop-helix transcription factor PIF4 and its downstream genes involved in auxin responses,which enhance cell division.In the current study,we discovered that cell wall-related calcium-binding protein 2(CCaP2)and its paralogs CCaP1 and CCaP3 function as positive regulators of thermo-responsive hypocotyl growth by promoting cell elongation in Arabidopsis.Interestingly,mutations in CCaP1/CCaP2/CCaP3 do not affect the expression of PIF4-regulated classic downstream genes.However,they do noticeably reduce the expression of xyloglucan endotransglucosylase/hydrolase genes,which are involved in cell wall modification.We also found that CCaP1/CCaP2/CCaP3 are predominantly localized to the plasma membrane,where they interact with the plasma membrane H^(+)-ATPases AHA1/AHA2.Furthermore,we observed that vanadate-sensitive H^(+)-ATPase activity and cell wall pectin and hemicellulose contents are significantly increased in wild-type plants grown at warm temperatures compared with those grown at normal growth temperatures,but these changes are not evident in the ccap1-1 ccap2-1 ccap3-1 triple mutant.Overall,our findings demonstrate that CCaP1/CCaP2/CCaP3 play an important role in controlling thermo-responsive hypocotyl growth and provide new insights into the alternative pathway regulating hypocotyl growth at warm temperatures through cell wall modification mediated by CCaP1/CCaP2/CCaP3.

Modified mesenchymal stem cells in cancer therapy: A smart weapon requiring upgrades for wider clinical applications

Mesenchymal stem stromal cells(MSC)are characterized by the intriguing capacity to home toward cancer cells after systemic administration.Thus,MSC can be harnessed as targeted delivery vehicles of cytotoxic agents against tumors.In cancer patients,MSC based advanced cellular therapies were shown to be safe but their clinical efficacy was limited.Indeed,the amount of systemically infused MSC actually homing to human cancer masses is insufficient to reduce tumor growth.Moreover,induction of an unequivocal anticancer cytotoxic phenotype in expanded MSC is necessary to achieve significant therapeutic efficacy.Ex vivo cell modifications are,thus,required to improve anti-cancer properties of MSC.MSC based cellular therapy products must be handled in compliance with good manufacturing practice(GMP)guidelines.In the present review we include MSCimproving manipulation approaches that,even though actually tested at preclinical level,could be compatible with GMP guidelines.In particular,we describe possible approaches to improve MSC homing on cancer,including genetic engineering,membrane modification and cytokine priming.Similarly,we discuss appropriate modalities aimed at inducing a marked cytotoxic phenotype in expanded MSC by direct chemotherapeutic drug loading or by genetic methods.In conclusion,we suggest that,to configure MSC as a powerful weapon against cancer,combinations of clinical grade compatible modification protocols that are currently selected,should be introduced in the final product.Highly standardized cancer clinical trials are required to test the efficacy of ameliorated MSC based cell therapies.

Carbon material-based anodes in the microbial fuel cells

For the performance improvement of microbial fuel cells(MFCs),the anode becomes a breakthrough point due to its influence on bacterial attachment and extracellular electron transfer(EET).On other level,carbon materials possess the following features:low cost,rich natural abundance,good thermal and chemical stability,as well as tunable surface properties and spatial structure.Therefore,the development of carbon materials and carbon-based composites has flourished in the anode of MFCs during the past years.In this review,the major carbon materials used to decorate MFC anodes have been systematically summarized,based on the differences in composition and structure.Moreover,we have also outlined the carbon material-based hybrid biofilms and carbon material-modified exoelectrogens in MFCs,along with the discussion of known strategies and mechanisms to enhance the bacteria-hosting capabilities of carbon material-based anodes,EET efficiencies,and MFC performances.Finally,the main challenges coupled with some exploratory proposals are also expounded for providing some guidance on the future development of carbon material-based anodes in MFCs.

Modified methods for isolation of pancreatic stellate cells from human and rodent pancreas

Primary cultures of pancreatic stellate cells（PSCs） remain an important basis for in vitro study.However,effective methods for isolating abundant PSCs are currently lacking.We report on a novel approach to isolating PSCs from normal rat pancreases and human pancreatic ductal adenocarcinoma（PDAC） tissue.After anaesthesia and laparotomy of the rat,a blunt cannula was inserted into the pancreatic duct through the anti-mesentery side of the duodenum,and the pancreas was slowly infused with an enzyme solution until all lobules were fully dispersed.The pancreas was then pre-incubated,finely minced and incubated to procure a cell suspension.PSCs were obtained after the cell suspension was filtered,washed and subject to gradient centrifugation with Nycodenz solution.Fresh human PDAC tissue was finely minced into 1×1×l mm^3 cubes with sharp blades.Tissue blocks were placed at the bottom of a culture plate with fresh plasma（EDTA-anti-coagulated plasma from the same patient,mixed with CaCL） sprinkled around the sample.After culture for 5-10 days under appropriate conditions,activated PSCs were harvested.An intraductal perfusion of an enzyme solution simplified the procedure of isolation of rat PSCs,as compared with the multiple injections technique,and a modified outgrowth method significantly shortened the outgrowth time of the activated cells.Our modification in PSC isolation methods significantly increased the isolation efficiency and shortened the culture period,thus facilitating future PSC-related research.

Spotlight on chimeric antigen receptor engineered T cell research and clinical trials in China

T cell mediated adoptive immune response has been characterized as the key to anti-tumor immunity. Scientists around the world including in China, have been trying to harness the power of T cells against tumors for decades. Recently, the biosynthetic chimeric antigen receptor engineered T cell(CAR-T) strategy was developed and exhibited encouraging clinical efficacy, especially in hematological malignancies. Chimeric antigen receptor research reports began in 2009 in China according to our Pub Med search results. Clinical trials have been ongoing in China since 2013 according to the trial registrations on clinicaltrials.gov.. After years of assiduous efforts, research and clinical scientists in China have made their own achievements in the CAR-T therapy field. In this review, we aim to highlight CAR-T research and clinical trials in China, to provide an informative reference for colleagues in the field.

Interfacial engineering of printable bottom back metal electrodes for full-solution processed flexible organic solar cells

Printing of metal bottom back electrodes of flexible organic solar cells（FOSCs） at low temperature is of great significance to realize the full-solution fabrication technology. However, this has been difficult to achieve because often the interfacial properties of those printed electrodes, including conductivity, roughness, work function,optical and mechanical flexibility, cannot meet the device requirement at the same time. In this work, we fabricate printed Ag and Cu bottom back cathodes by a low-temperature solution technique named polymer-assisted metal deposition（PAMD） on flexible PET substrates. Branched polyethylenimine（PEI） and ZnO thin films are used as the interface modification layers（IMLs） of these cathodes. Detailed experimental studies on the electrical, mechanical, and morphological properties, and simulation study on the optical properties of these IMLs are carried out to understand and optimize the interface of printed cathodes. We demonstrate that the highest power conversion efficiency over 3.0% can be achieved from a full-solution processed OFSC with the device structure being PAMDAg/PEI/P3 HT：PC61BM/PH1000. This device also acquires remarkable stability upon repeating bending tests.