Immunogenic aspects of stem cell therapy in regenerative medicine

Departamentul de Medicină, Diviziunea de Cardiologie, Diviziunea de Medicină Genomică, Departmentul de Fizioterapie și Științe ale Sănătății, Centrul Medical „George Washington”, Washington, DCUtilizarea celulelor stem pentru regenerarea și repararea țesuturilor deteriorate a fost de interes pentru comunități științifice și profesioniști timp de câteva decenii. Studiile de translație în cercetările de medicină regenerativă au scopul de a facilita transferul cunoștințelor științifice de bază ce țin de biologia celulelor stem în opțiuni terapeutice posibile. Celulele stem au un potențial promițător pentru aplicarea acestora în repararea sau regenerarea organelor și țesuturilor. Totuși, rata de supraviețuire a celulelor stem transplantate nu a fost una optimă și varia în funcţie de metodele de livrare și tipul celulelor. Unul dintre mecanismele de transplantare care au eșuat este reacția imună a gazdei împotriva celulelor stem livrate. În cadrul acestei analize se vor discuta datele disponibile în literatura despre sursele de celule stem, imunogenitatea diferitor tipuri de celule stem și liniile lor descendente, precum și potențialele strategii de îmbunătățire a supraviețuirii și eficacitatea transplantării celulelor stem în medicina regenerativă.Using stem cells to regenerate and repair damaged tissue has been a focus of the scientific communities and medical professionals for the last couple of decades. Translational studies in regenerative medicine research are intended to facilitate the transfer of the basic science knowledge of stem cell biology into potential therapeutic options. Stem cells have a promising potential for application in repair or regeneration of organs and tissues. However, the survival rate of the transplanted stem cells has not been optimal and varies depending on the delivery methods and type of cells. One of the mechanisms of the failed transplantations is the host’s immune reaction against the delivered stem cells. In this review, we will discuss the available data in the literature on sources of stem cells, the immunogenicity of different types of stem cells and their progeny lineages, and the potential strategies to improve the survival and the efficacy of the stem cells transplantation in regenerative medicine.https://stiinta.usmf.md/sites/default/files/2018-09/MJHS%20nr.%201_2014.pd

Development of solar fuels photoanodes through combinatorial integration of Ni-La-Co-Ce oxide and Ni-Fe-Co-Ce oxide catalysts on BiVO_4

The development of an efficient, stable photoanode to provide protons and electrons to the (photo)cathode remains a primary materials challenge in the establishment of a scalable technol. for solar fuels generation. The typical photoanode architecture consists of a semiconductor light absorber coated with a metal oxide that serves a combination of functions, including corrosion protection, electrocatalysis, light trapping, hole transport, and elimination of deleterious recombination sites. To provide a more efficient exploration of metal oxide coatings for a given light absorber, we introduce a high throughput methodol. wherein a uniform BiVO_4 library is coated with 858 unique metal oxides covering a range of metal oxide loadings and the full Ni-La-Co-Ce oxide or Ni-Fe-Co-Ce oxide psuedo-quaternary compn. spaces. Photoelectrochem. characterization of each photoanode reveals that approx. one third of the coatings lower the photoanode performance while select combinations of metal oxide compn. and loading provide up to a 14-fold increase in the max. photoelectrochem. power generation for oxygen evolution in pH 13 electrolyte. Particular Ce-rich coatings also exhibit an anti-reflection effect that further amplifies the performance, yielding a 20-fold enhancement in power conversion efficiency compared to bare BiVO_4. By use of in situ optical spectroscopy and comparisons between the metal oxide coatings and their extrinsic optical and electrocatalytic properties, we present a suite of data-driven discoveries, including compn. regions which form optimal interfaces with BiVO_4 and photoanodes that are suitable for integration with a photocathode due to their excellent power conversion and solar transmission efficiencies. The initial high throughput discoveries were extended and validated through follow-up high throughput investigations and conventional photoelectrochem. measurements. The high throughput experimentation and informatics provides a powerful platform for both identifying the pertinent interfaces for further study and discovering high performance photoanodes for incorporation into efficient water splitting devices

Deep Sequencing Transcriptome Analysis of Murine Wound Healing: Effects of a Multicomponent, Multitarget Natural Product Therapy-Tr14

Wound healing involves an orchestrated response that engages multiple processes, such as hemostasis, cellular migration, extracellular matrix synthesis, and in particular, inflammation. Using a murine model of cutaneous wound repair, the transcriptome was mapped from 12 h to 8 days post-injury, and in response to a multicomponent, multi-target natural product, Tr14. Using single-molecule RNA sequencing (RNA-seq), there were clear temporal changes in known transcripts related to wound healing pathways, and additional novel transcripts of both coding and non-coding genes. Tr14 treatment modulated \u3e100 transcripts related to key wound repair pathways, such as response to wounding, wound contraction, and cytokine response. The results provide the most precise and comprehensive characterization to date of the transcriptome\u27s response to skin damage, repair, and multicomponent natural product therapy. By understanding the wound repair process, and the effects of natural products, it should be possible to intervene more effectively in diseases involving aberrant repair

Correlating Oxidation State and Surface Area to Activity from Operando Studies of Copper CO Electroreduction Catalysts in a Gas-fed Device

The rational design of high-performance electrocatalysts requires a detailed understanding of dynamic changes in catalyst properties, including oxidation states, surface area, and morphology under realistic working conditions. Oxide-derived Cu catalysts exhibit a remarkable selectivity toward multicarbon products for the electrochemical CO reduction reaction (CORR), but the exact role of the oxide remains elusive for explaining the performance enhancements. Here, we used operando X-ray absorption spectroscopy (XAS) coupled with simultaneous measurements of the catalyst activity and selectivity by gas chromatography (GC) to study the relationship between oxidation states of Cu-based catalysts and the activity for ethylene (C₂H₄) production in a CO gas-fed cell. By utilizing a custom-built XAS cell, oxidation states of Cu catalysts can be probed in device-relevant settings and under high current densities (>80 mA cm⁻²) for the CORR. By employing an electrochemical oxidation process, we found that the Cu oxidation states and specific ion species do not correlate with C₂H₄ production. The difference in the CORR activity is also investigated in relation to electrochemical surface area (ECSA) changes. While the hydrogen evolution reaction (HER) activity is positively correlated to the ECSA changes, the increased C₂H₄ activity is not proportional to the ECSA. Ex situ characterization from microscopic techniques suggests that the changes in the C₂H₄ activity and selectivity may arise from a morphological transformation that evolves into a more active structure. These comprehensive results give rise to the development of a cell regeneration method that can restore the performance of the Cu catalyst without cell disassembly. Our study establishes a basis for the rational design of highly active electrocatalysts for broad-range reactions in a gas-fed device

Development of solar fuels photoanodes through combinatorial integration of Ni-La-Co-Ce oxide and Ni-Fe-Co-Ce oxide catalysts on BiVO_4

The development of an efficient, stable photoanode to provide protons and electrons to the (photo)cathode remains a primary materials challenge in the establishment of a scalable technol. for solar fuels generation. The typical photoanode architecture consists of a semiconductor light absorber coated with a metal oxide that serves a combination of functions, including corrosion protection, electrocatalysis, light trapping, hole transport, and elimination of deleterious recombination sites. To provide a more efficient exploration of metal oxide coatings for a given light absorber, we introduce a high throughput methodol. wherein a uniform BiVO_4 library is coated with 858 unique metal oxides covering a range of metal oxide loadings and the full Ni-La-Co-Ce oxide or Ni-Fe-Co-Ce oxide psuedo-quaternary compn. spaces. Photoelectrochem. characterization of each photoanode reveals that approx. one third of the coatings lower the photoanode performance while select combinations of metal oxide compn. and loading provide up to a 14-fold increase in the max. photoelectrochem. power generation for oxygen evolution in pH 13 electrolyte. Particular Ce-rich coatings also exhibit an anti-reflection effect that further amplifies the performance, yielding a 20-fold enhancement in power conversion efficiency compared to bare BiVO_4. By use of in situ optical spectroscopy and comparisons between the metal oxide coatings and their extrinsic optical and electrocatalytic properties, we present a suite of data-driven discoveries, including compn. regions which form optimal interfaces with BiVO_4 and photoanodes that are suitable for integration with a photocathode due to their excellent power conversion and solar transmission efficiencies. The initial high throughput discoveries were extended and validated through follow-up high throughput investigations and conventional photoelectrochem. measurements. The high throughput experimentation and informatics provides a powerful platform for both identifying the pertinent interfaces for further study and discovering high performance photoanodes for incorporation into efficient water splitting devices

Discovery of Fe–Ce Oxide/BiVO_4 Photoanodes through Combinatorial Exploration of Ni–Fe–Co–Ce Oxide Coatings

An efficient photoanode is a prerequisite for a viable solar fuels technology. The challenges to realizing an efficient photoanode include the integration of a semiconductor light absorber and a metal oxide electrocatalyst to optimize corrosion protection, light trapping, hole transport, and photocarrier recombination sites. To efficiently explore metal oxide coatings, we employ a high-throughput methodology wherein a uniform BiVO_4 film is coated with 858 unique metal oxide coatings covering a range of metal oxide loadings and the full (Ni–Fe–Co–Ce)O_x pseudoquaternary composition space. Photoelectrochemical characterization of the photoanodes reveals that specific combinations of metal oxide composition and loading provide up to a 13-fold increase in the maximum photoelectrochemical power generation for oxygen evolution in pH 13 electrolyte. Through mining of the high-throughput data we identify composition regions that form improved interfaces with BiVO_4. Of particular note, integrated photoanodes with catalyst compositions in the range Fe_((0.4–0.6))Ce_((0.6–0.4))O_x exhibit high interface quality and excellent photoelectrochemical power conversion. Scaled-up inkjet-printed electrodes and photoanodic electrodeposition of this composition on BiVO_4 confirms the discovery and the synthesis-independent interface improvement of (Fe–Ce)O_x coatings on BiVO_4

Genomic profiling reveals the potential role of TCL1A and MDR1 Deficiency in chemotherapy-induced cardiotoxicity

Background: Anthracyclines, such as doxorubicin (Adriamycin), are highly effective chemotherapeutic agents, but are well known to cause myocardial dysfunction and life-threatening congestive heart failure (CHF) in some patients. Methods: To generate new hypotheses about its etiology, genome-wide transcript analysis was performed on whole blood RNA from women that received doxorubicin-based chemotherapy and either did, or did not develop CHF, as defined by ejection fractions (EF)≤40%. Women with non-ischemic cardiomyopathy unrelated to chemotherapy were compared to breast cancer patients prior to chemo with normal EF to identify heart failure-related transcripts in women not receiving chemotherapy. Byproducts of oxidative stress in plasma were measured in a subset of patients. Results: The results indicate that patients treated with doxorubicin showed sustained elevations in oxidative byproducts in plasma. At the RNA level, women who exhibited low EFs after chemotherapy had 260 transcripts that differed \u3e2-fold (pIn vitro studies confirmed that inhibition of MDR1 by verapamil in rat H9C2 cardiomyocytes increased their susceptibility to doxorubicin-induced toxicity. Conclusions: It is proposed that chemo-induced cardiomyopathy may be due to a reduction in TCL1A levels, thereby causing increased apoptotic sensitivity, and leading to reduced cardiac MDR1 levels, causing higher cardiac levels of doxorubicin and intracellular free radicals. If so, screening for TCL1A and MDR1 SNPs or expression level in blood, might identify women at greatest risk of chemo-induced heart failure