Stem cell and Regenerative medicine

Differentiation is a key cellular process in normal tissue development that is significantly altered in cancer. Although molecular signatures characterising pluripotency and multipotency exist, there is, as yet, no single quantitative mark of a cellular sample's position in the global differentiation hierarchy. Here we adopt a systems view and consider the sample's network entropy, a measure of signaling pathway promiscuity, computable from a sample's genome-wide expression profile. We demonstrate that network entropy provides a quantitative, in-silico, readout of the average undifferentiated state of the profiled cells, recapitulating the known hierarchy of pluripotent, multipotent and differentiated cell types. Network entropy further exhibits dynamic changes in time course differentiation data, and in line with a sample's differentiation stage. In disease, network entropy predicts a higher level of cellular plasticity in cancer stem cell populations compared to ordinary cancer cells. Importantly, network entropy also allows identification of key differentiation pathways. Our results are consistent with the view that pluripotency is a statistical property defined at the cellular population level, correlating with intra-sample heterogeneity, and driven by the degree of signaling promiscuity in cells. In summary, network entropy provides a quantitative measure of a cell's undifferentiated state, defining its elevation in Waddington's landscape. T he observed diversity of mature cells and human tissues arises as a result of a complex, intricate program of cellular differentiation, ultimately originating from (pluripotent) embryonic stem cells 1 . Although systems biology principles underpinning the transitions between specific cellular states, such as pluripotency and progenitor states, are in the process of being elucidated 2-5 , much remains to be learned. In the case of hematopoiesis, one of the best understood developmental systems, the full repertoire of transcription factors and signaling pathways dictating cell-fate is still unknown . Other studies have focused on characterising the pluripotent and progenitor states in terms of genome-wide gene expression , DNA methylation and chromatin state profiles . Although these molecular signatures can discriminate cells of specific differentiation stages from each other, there is, as yet, no single quantitative measure that can correctly place a sample within the global differentiation hierarchy. Rephrased in the context of Waddington's differentiation landscape 21 , we do not yet have a molecular measure that can represent the energy potential, i.e. the elevation, in Waddington's landscape. Recently, it has been proposed that pluripotency, and more generally, the undifferentiated state, is an emergent statistical property of a population of cells , not well-defined at the single-cell level. Specifically, it has been argued that high cellular diversity underpins the pluripotent or multipotent capacity of stem cell populations, with differentiated cell populations representing a more uniform synchronised state 22 . Motivated by this, we here explore a system's property of a cellular sample, called network entropy, in the context of cellular differentiation. At the single-cell level network entropy can be thought of as an approximate measure of signaling pathway promiscuity . Thus, a highly undifferentiated cell, such as a pluripotent stem cell, would have a high network

Biodentine is a tricalcium silicate-based cement material that has a great impact on different biological processes, compared to other biomaterials. Therefore, we aimed to investigate the biocompatibility of Biodentine with stem cells derived from periodontal ligament (PDLSCs), by determining cell proliferation, cytotoxicity, migration, adhesion and mineralization potential. PDLSCs were treated with Biodentine™

Human Mesenchymal Stem Cells (hMSCs) have immunomodulatory properties, mainly through their paracrine secretions, which contain anti-inflammatory molecules and exosomes. The favourable characteristics of hMSCs in the regeneration of damaged tissues have caused these cells to be considered a therapeutic approach in immune-related diseases. However, the cell therapy approach requires a detailed understanding of the behaviour of hMSCs in the inflammatory microenvironment of target tissues because MSCs may respond differently to this pathological microenvironment compared to normal physiological conditions. In addition, the level of influence that effective mechanisms of hMSCs, including paracrine approaches and cell contact, have on maintaining homeostasis and repairing damaged tissues is a subject of ongoing controversy. hMSCs show different characteristics in vitro and in vivo depending on their tissue of origin. This variability is more apparent when the cells are derived from different donors, with fetal and adult sources showing different regenerative capabilities. Furthermore, the fact that hMSCs behave differently depending on the local microenvironment adds to the complexity of understanding the immunological pathways mediated by hMSCs. Previous research has demonstrated that the origin of MSCs (fetal or adult) has a significant impact on their immunological characteristics. This is due to differences in the cells' mechanisms of cell contact and paracrine secretion, which ultimately affect the microenvironment of the MSCs. This study aims to review the immunomodulatory and immunogenic features of fetal and adult/somatic MSCs to highlight the effect of the cell source on paracrine secretions and the resulting microenvironment, both during in vitro expansion and in vivo after cell administration.

Amniotic fluid (AF) serves as a protective medium for the developing fetus and is a rich source of biologically active components, including fetal stem cells and extracellular vesicles (EVs). Notably, mesenchymal stem cells (MSCs) and human amniotic epithelial cells (hAECs) in AF possess pluripotent-like characteristics, contributing to the development of therapeutic strategies. This review aims to explore the therapeutic potential of AF-derived stem cells (AFSCs) in regenerative medicine and immunotherapy. The review consolidates findings on the Mesenchymal Stem Cells (MSCs) and human amniotic epithelial cells (hAECs) stand out for their pluripotent-like characteristics, with hAECs originating from epiblast-derived stem cells. AF-MSCs offer several advantages over adult MSCs, addressing ethical concerns and showcasing therapeutic potential. The distinctive biological attributes of AF, including its components and derived cells, make it a promising candidate for therapeutic applications in regenerative medicine and immunotherapy strategies. Further research is warranted to elucidate specific clinical applications and mechanisms underlying its beneficial properties.

Wound healing is a complex process and rapid healing necessitates a proper micro-environment. Therefore, design and fabrication of an efficacious wound dressing is an impressive innovation in the field of wound healing. The fabricated wound dressing in this scenario was designed using a combination of the appropriate coagulating and anti-bacterial materials like fibrinogen (as coagulating agent), nisin (as anti-bacterial agent), ethylenediaminetetraacetic acid (as anti-bacterial agent), and alginate (as wound healing agent). Biophysical characterization showed that the interaction of fibrinogen and alginate was associated with minor changes in the secondary structure of the protein. Conformational studies showed that the protein was structurally stable at 42 °C, is the maximum temperature of the infected wound. The properties of the hydrogel such as swelling, mechanical resistance, nisin release, antibacterial activity, cytotoxicity, gel porosity, and blood coagulation were assessed...

Two patients with chronic cervical spinal cord injury and quadriplegia underwent partial resection of the medular scar and implant of bone marrow tissue with a combination of drugs at the site of spinal cord injury. Post-operatively they received a similar treatment in the neuromotor rehabilitation centre and were treated additionally with cerebrolysin . Sensory improvements were noticed, but no significant motor improvements were observed twenty months afterwards.

Smart biomaterials that can self-adapt or respond to microenvironmental factors or external signals hold excellent potential for a variety of biomedical applications, from biosensing, drug delivery, and cell therapy to tissue engineering. The complexity of smart biomaterials, including the rational design of their structure and composition, the accurate analysis and prediction of their

Inflammatory response in COVID-19 contributes greatly to disease severity. Mesenchymal Stem Cells (MSCs) have the potential to alleviate inflammation and reduce mortality and length of stay in COVID-19 patients. We investigated the safety and effectiveness of normoxic-allogenic umbilical cord (NA-UC)-MSCs as an adjunctive treatment in severe COVID-19 patients. A double-blind, multicentric, randomized, placebo-controlled trial involving severe COVID-19 patients was performed from January–June 2021 in three major hospitals across Java, Indonesia. Eligible participants (n = 42) were randomly assigned to two groups (1:1), namely the intervention (n = 21) and control (n = 21) groups. Either NA-UC-MSCs or NaCl placebo were administered daily. The primary outcome was the duration of hospitalization. Meanwhile, the secondary outcomes were radiographical progression (Brixia score), respiratory and oxygenation parameters, and inflammatory markers, in addition to the safety profile of NA-UC-MS...

Background/aim: Dendritic cells (DCs) are important immune mediators following allogeneic hematopoietic stem cell transplantation (HSCT). We screened for DC frequency in the cornea and oral mucous membranes after HSCT by confocal laser scanning microscopy (CLSM) in a canine model. Materials and methods: In vivo CLSM images of the epithelia were taken the day before and on days 28, 56 and 112 following HSCT. Peripheral blood counts and chimerism were determined. Results: An increase of DCs after HSCT was detected in each animal in both investigated tissue types. Highest DC numbers in the flew and the gingiva were detected on day 28 and in the corneal epithelium on day 56 after HSCT, respectively. Conclusion: Changes of DCs in ocular and non-ocular mucous membranes can be monitored by CLSM in vivo. The DC frequency in the cornea and mucosa changes following HSCT. DC recovery is rapid and their numbers correlate with the development of chimerism of peripheral blood mononuclear cells.

Osteoarthritis is a degenerative disease of the cartilage that affects millions. Its pathology is characterized by catabolic and anabolic factors that can be modified due to age, weight and genetics to increase the severity of deterioration. Current standards of care may manage symptoms, but there is currently no proven treatment of osteoarthritis to reverse degeneration and build back the ECM. Due to this, stem cells have been investigated as a potential therapy. This is because of their unique abilities to differentiate into many cell types and even regenerate tissue. Mesenchymal stem cells have been targeted specifically because of their high reproduction rate and many other important factors. Studies done have concluded that there are statistically significant benefits in treating osteoarthritic joints with mesenchymal stem cells derived from adipose tissue and umbilical cord tissue as well as synovial. Although these benefits have been recorded, it is still imperative that further studies be conducted to test the longevity of the treatment and its possible negative side effects.

The ‘Ashtamudi’ as the name implies is a lake with eight prominent arms and is one of the largest wetland ecosystems in Kerala, flourished with immense life verities. Sonneratia alba (Mangrove apple), Acanthus ilicifolius (Sea Holly, Shore purslane), etc are a few numbered species that are recently reported as significant phyto-chemical storage apart from their conventional utility as a mangrove. Percentage of foliage cover by these two species was observed for the year 2010-11 and 2014-15. The study report in the year 201415, the cumulative foliage cover by these two species fall to 72% (49% and 23% respectively)from 81% in the year 2010-11 (57% and 24% respectively). An overlap of both the species were also found by about 8% in the year 2010-11 and it remains the same for the year 2014-15. The water samples collected from the 20 different zones of the lake in the year 2010-11 represents half of polluted and the another half as of unpolluted, The study was repeated by analysing the...

Las úlceras por presión son producto de una necrosis isquémica en la piel y tejido subcutáneo, se presentan en pacientes inmovilizados poretiología diversa, y en estadios avanzados incrementan la mortalidad. La terapia celular con Células Madre Somáticas, que se diferencian y proliferan a células maduras funcionalmente normales, tiene la finalidad de reparar la función de tejidos lesionados. Objetivo.-Evidenciar la eficacia de las Células Madre Somáticas de médula ósea en la reparación de úlceras crónicas por presión, como una posibilidad terapéutica en los tratamientos convencionales no exitosos. Método.-Se estudió 4 pacientes con úlceras crónicas por presión en estadios avanzados yrefractarias a tratamiento convencional.Se obtuvo Células Madre Somáticas de la médula ósea del esternón, y se procedió al sembrado de las mismas una vez por semana. Resultados.-Las Células Madre Somáticas sembradas en las úlceras crónicas se diferenciaron en tejido muscular, conjuntivo, subcutáneo y epitelial en un periodo comprendido entre 30 a 69 días. Conclusión.-La terapia celular con Células Madre Somáticas de médula ósea se constituye en una posibilidad terapéutica en úlceras crónicas de estadios avanzados y refractarias a tratamiento convencional.

Background and purpose: Delayed wound healing is a common complication of diabetes mellitus. However, less is known about the cause of this pathology. Types of skin cells, extracellular matrix and variety of growth factors are involved in wound healing. The use of recombinant growth factors in researches and production of skin substitutes are still a challenge. Much research has been done on the effects of gene therapy and cell therapy in wound healing. This experimental study assessed the effect of insulin-like growth factor (IGF-1) over expression in combination with fibroblast cells therapy to diabetic wounds in rats. Material and methods: Diabetes was induced in rats using Streptozotocin. Fibroblasts were cultured and transfected with IGF-1. Lipofectamine 2000 was used as reagent transfection and transgene expression levels were measured by ELIZA. To study the in vivo, rats (weighing 170-200g) were randomly divided into three groups (5/group) and full-thickness wounds were created on the dorsum region. Suspensions of transfected fibroblast and native fibroblast cells were injected into the wound and were compared with the wounds treated with normal saline. For microscopic examination, biopsy was performed on day 8. Results: In in vitro, the maximum expression of IGF-1 in transfected fibroblast cells (96.95 pg/ml) was 24 h after gene transfer. In vivo, IGF-1 gene therapy increased the number of fibroblast and keratinocyte cells in wound healing process. Granulation tissue formation in transfected fibroblast and native fibroblast cells groups compared with the normal saline group were found to be more organized. The expression of IGF-1 increased by optimization of gene transfer. High concentrations of IGF-1, in combination with cell therapy, had a significant effect on delayed wound healing in diabetic rats.

Stem progenitor cells serve as a functional reserve and may differentiate into mature cells with a different phenotype. Partially differentiated endothelial progenitor cells (EPCs) are characterized by the expression of surface molecules such as endoglin (CD105), vWF, PECAM-1/CD31, CD146, CD62E, CD51/61, CD106, CD41a, CD41b, CD34 and AC133, The first clinical studies in peripheral and coronary artery disease revealed the clinical efficacy of human bone marrow-derived mononuclear fraction in diminishing the adverse effects of peripheral and myocardial ischaemia. No significant side-effects of the EPC application were observed, but further studies are required to confirm the long-term safety and efficacy of this method as well as to assess its possible hazards.

Branched epithelia determine the anatomy of many mammalian organs; understanding how they develop is therefore an important element of understanding organogenesis as a whole. In recent years, much progress has been made in identifying paracrine factors that regulate branching morphogenesis in many organs, but comparatively little attention has been paid to the mechanisms of morphogenesis that translate these signals into anatomical change. Localized cell proliferation is a potentially powerful mechanism for directing the growth of a developing system to produce a specific final morphology. We have examined the pattern of cell proliferation in the ureteric bud system of the embryonic murine metanephric kidneys developing in culture. We detect a zone of high proliferation at the site of the presumptive ureteric bud even before it emerges from the Wolffian duct and later, as ureteric bud morphogenesis continues, proliferation is localized mainly in the very tips of the branching epithelium. Blocking cell cycling using methotrexate inhibits ureteric bud emergence. The proliferative zone is present at ureteric bud tips only when they are undergoing active morphogenesis; if branching is inhibited either by treatment with natural negative regulators (TGFβ ) or with antagonists of natural positive regulators (GDNF, glycosaminoglycans) then proliferation at the tips falls back to levels characteristic of the stalks behind them. Our results suggest that localized proliferation is an important morphogenetic mechanism in kidney development.

Background and Aim: Angiogenesis and anti-apoptosis play crucial roles in ischemic stroke recovery. The mesenchymal stem cell (MSC) secretome, rich in bioactive molecules, presents a promising therapeutic avenue. However, optimizing the culture conditions to enhance the expression of angiogenic markers remains a challenge. This study examines the effect of hypoxic preconditioning on the expression of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), and microRNA (miRNA-128) in the secretome of umbilical cord-derived MSCs (UC-MSCs) from Macaca fascicularis.

Materials and Methods: UC-MSCs were cultured under normoxic (21% O2) and hypoxic conditions (1%, 3%, and 5% O2) for 48 h. The secretome was isolated, and reverse transcription-quantitative polymerase chain reaction was used to quantify the expression of VEGF, MCP-1, MMP-2, and miRNA-128. Expression levels were normalized to housekeeping genes and analyzed using statistical methods to determine significant differences among groups.

Results: Hypoxic preconditioning significantly upregulated VEGF (1% O2), MCP-1 (5% O2), and miRNA-128 (5% O2) expression compared to normoxic conditions. Conversely, MMP-2 expression was highest in normoxic conditions and downregulated under hypoxia. In addition, miRNA-128 was found to be predominantly secreted into the extracellular space under hypoxic conditions rather than retained within cells.

Conclusion: Hypoxic preconditioning effectively modulates the expression of key angiogenesis and anti-apoptotic markers in UC-MSCs. The study highlights the importance of optimizing oxygen levels to enhance the therapeutic potential of MSCderived secretomes for ischemic stroke treatment. Future research should focus on in vivo validation and clinical translation of these findings.

Keywords: angiogenesis, hypoxic preconditioning, ischemic stroke, mesenchymal stem cells, microRNA-128, secretome.

This study presents a novel interdisciplinary approach examining the potential influence of acoustic modulation and bioelectric signalling on cancerous cells. While traditional cancer treatments involve chemotherapy, radiation, and surgery, emerging research suggests that electromagnetic and sound frequencies may play a role in Cellular resonance disruption, apoptosis induction, and metabolic interference. The study explores three targeted sound applications: bioelectric modulation (125 Hz pulsed at 7.83 Hz), Resonance disruption (528 Hz and 4 kHz tones), and binaural beats (400 Hz left ear, 410 Hz right ear creating a 10 Hz beat). Cancerous cells exhibit distinct vibrational and bioelectric properties, making them susceptible to frequency-based interventions. This research examines whether acoustic waves can indirectly impact cancer cell activity, metabolism, and immune responses by delivering specific frequencies through auditory stimulation and bioelectromagnetic pathways. Experimental validation will involve laboratory exposure of cancer cell cultures (e.g., HeLa, MCF-7, A549) to modulated sound waves, with effects assessed through microscopy, apoptosis assays, mitochondrial function analysis, and bioelectric potential measurements. If validated, this research may provide a foundation for noninvasive complementary cancer therapies that integrate biophysics, aeroacoustics, and cellular bioelectricity.

Cell differentiation in multicellular organisms has the obvious function during development of creating new cell types. However, in long-lived organisms with extensive cell turnover, cell differentiation often continues after new cell types are no longer needed or produced. Here, we address the question of why this is true. It is believed that multicellular organisms could not have arisen or been evolutionarily stable without possessing mechanisms to suppress somatic selection among cells within organisms, which would otherwise disrupt organismal integrity. Here, we propose that one such mechanism is a specific pattern of ongoing cell differentiation commonly found in metazoans with cell turnover, which we call ''serial differentiation.'' This pattern involves a sequence of differentiation stages, starting with self-renewing somatic stem cells and proceeding through several (non-self-renewing) transient amplifying cell stages before ending with terminally differentiated cells. To test the hypothesis that serial differentiation can suppress somatic evolution, we used an agent-based computer simulation of cell population dynamics and evolution within tissues. The results indicate that, relative to other, simpler patterns, tissues organized into serial differentiation experience lower rates of detrimental cell-level evolution. Self-renewing cell populations are susceptible to somatic evolution, while those that are not self-renewing are not. We find that a mutation disrupting differentiation can create a new self-renewing cell population that is vulnerable to somatic evolution. These results are relevant not only to understanding the evolutionary origins of multicellularity, but also the causes of pathologies such as cancer and senescence in extant metazoans, including humans.

Previous IRB-approved studies demonstrated that a rare population of endogenous adult telomerase positive stem cells (aTPSCs), isolated and activated ex vivo, displayed a 100% safety record for reinfusion and an 86% efficacy at reversing signs and symptoms in 97 individuals in 18 disease states. Recent studies demonstrated that these rare aTPSCs could also be activated in vivo by ingestion of a combinatorial nutraceutical supplement pill (CNSP). With IRB permission, CNSP was originally developed for an individual too fragile to undergo the fresh isolate aTPSC technologies. Without any other medical intervention, ingestion of CNSP for 12 months raised his ejection fraction from <10% to about 50%. Based on the results from his study (n=1) [100% safe and 100% efficacious], we received IRB permission to expand the number of clinical trials to determine the effectiveness of using CNSP for other health concerns. Herein, are the preliminary results from 40 people in 28 health concerns utilizing CNSP only and CNSP with other treatment modalities, to affect a better quality of life. Participants were assessed in phase-0, open access, open ended clinical trials, for 1-4+ years. Participants in all 28 clinical trials demonstrated 100% safety and 100% efficacy at reversing signs and symptoms in their respective health concerns, giving them an apparent better quality of life.

No hay legislación específica sobre la investigación en embriones humanos. Brasil: Permite la investigación con CME. No tiene legislación, pero permite la creación de embriones para la investigación. Dinamarca: Prohibida. Los embriones sobrantes se destruyen enseguida. España. Solo permite la investigación con embriones no viables. Estados Unidos: Permite la investigación pero con dineros privados.

Bovine adipose-derived stem cells were obtained from the subcutaneous abdominal adipose tissue. The cells were cultured by the modified tissue-explants method developed in our laboratory, and then analyzed using optical microscopy and flow cytometry. These cells were able to replicate in our cell culture conditions. cell Flow cytometry showed that bovine adipose-derived stem cells expressed mesenchymal stem cell markers (CD73 and CD90). Meanwhile, haematopoietic markers (CD45 and CD34) are absent from bovine adipose-derived stem cells. We also induced their adipogenic differentiation in vitro.

Purpose To investigate the therapeutic potential of extracellular vesicles (EVs) derived from human nucleus pulposus cells (NPCs), with a specific emphasis on Tie2-enhanced NPCs, compared to EVs derived from human bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a coccygeal intervertebral disc degeneration (IDD) rat model. Methods EVs were isolated from healthy human NPCs cultured under standard (NPC STD -EVs) and Tie2-enhancing (NPC Tie2+ -EVs) conditions. EVs were characterized, and their potential was assessed in vitro on degenerative NPCs in terms of cell proliferation and senescence, with or without 10 ng/mL interleukin (IL)-1β. Thereafter, 16 Sprague-Dawley rats underwent annular puncture of three contiguous coccygeal discs to develop IDD. Phosphate-buffered saline, NPC STD -EVs, NPC Tie2+ -EVs, or BM-MSC-derived EVs were injected into injured discs, and animals were followed for 12 weeks until sacrifice. Behavioral tests, radiographic disc height index (DHI) measurements, evaluation of pain biomarkers, and histological analyses were performed to assess the outcomes of injected EVs. Results NPC-derived EVs exhibited the typical exosomal morphology and were efficiently internalized by degenerative NPCs, enhancing cell proliferation, and reducing senescence. In vivo, a single injection of NPC-derived EVs preserved DHI, attenuated degenerative changes, and notably reduced mechanical hypersensitivity. MSC-derived EVs showed marginal improvements over sham controls across all measured outcomes. Conclusion Our results underscore the regenerative potential of young NPC-derived EVs, particularly NPC Tie2+ -EVs, surpassing MSC-derived counterparts. These findings raise questions about the validity of MSCs as both EV sources and cellular therapeutics against IDD. The study emphasizes the critical influence of cell type, source, and culture conditions in EV-based therapeutics.

The present study was carried out for optimization of protocols for conversion of porcine urinary bladder into bladder acellular matrix graft (BAMG) using different biological detergents and enzymes for tissue engineering. The tissue treated with enzyme and biological detergents at different concentration showed more dissolution and only few remnants of tissue were left and were not appropriate for grafting purpose. Therefore, enzyme treatment was omitted and tissue was directly treated with different concentrations of biological detergents for different time intervals. In the present study, the bladder graft treated with 0.5% SDS for 24 h showed complete acellularity with normal collagen fibres arrangement.

Planarians have a remarkable ability to regenerate lost body parts, including the brain, auricle, eye spots, etc.
They have been excellent model systems for pharmaceutical studies, including regenerative medicine, toxicology
and drug testing. An overview of currently available planarian model species used for studying the effects of
contaminants and pharmaceuticals on regeneration is important for initiating studies in laboratories for the
first time and developing indigenous model species. The present study provides a list of currently used planarian
model species around the globe and in India. The analysis highlights the lack of taxonomic studies providing
accurate identification of planarian species in India and unavailability of indigenous model species.

Bu calismada kanatli proventrikuluslarinda vaskuler endotelyal buyume faktoru (VEGF) ve reseptorlerinin (flt1/fms, flk1/KDR) fizyolojik rollerini daha iyi anlamak icin, immunohistokimya kullanilarak hucresel lokalizasyonlari incelendi. Calismanin materyalini 10 adet (5 erkek ve 5 disi) tavuk olusturdu. Proventrikulustan elde edilen doku ornekleri rutin histolojik islemler icin % 10 formol-alkolde tespit edildi. Kanatli proventrikuluslarinda luminal ve bez epitel hucreleri, stromal ve duz kas hucreleri ile damarlarin endotel ve duz kas hucrelerinin VEGF ve reseptorleri icin pozitif immunreaksiyon gosterdigi belirlendi. Bununla birlikte VEGF ve reseptorlerinin bez epitel hucrelerinde daha guclu sitoplazmik bir ekspresyon gosterdigi saptandi. Sonuc olarak VEGF ve reseptorlerinin kanatli proventrikulusundaki non-endotelyal hucrelerde cogalma, farklilasma, apopitozis ve anjiogenezisin saglanmasinda kritik bir rolunun olabilecegi dusunulmustur.

ABSTRACT. THE AUTHORS HYPOTHESIZE that stem/progenitor cells from umbilical cord blood are safe and promising for various brain injuries and disorders. A six month pilot study predicated on parental observations and completed questionnaires concerning the responses of cerebral palsy-stricken children to treatment with umbilical cord stem cells was launched during 2004. As part of this Mexican study, eight children (3–12 years of age) diagnosed with cerebral palsy underwent transplants with 1.5 million stem/progenitor cells (CD34+ and CD133+) that had been purified and ex-panded from the American Association of Blood Banks (AABB)-certified human umbilical cord blood. According to parent tendered observational re-ports, none of the children had graft versus host reactions. Eight out of eight children showed some improvement in mobility and/or cognitive function. Six children (75%) were rated as improving in muscle tone, hip movement, leg movement, rolling to the side, balancing while ...

This study aims to provide a comprehensive review of the ethical, legal and social issues in human brain organoid research, with a view to different types of research and applications: in vitro research, transplantation into nonhuman animals, and biocomputing. Despite the academic and societal attention on the possibility that human brain organoids may be conscious, we have identified diverse issues in human brain organoid research and applications. To guide the complex terrain of human brain organoid research and applications, a multidisciplinary approach that integrates ethical, legal, and social perspectives is essential.

Objective: This study aims to develop and evaluate an innovative implantable drug delivery system using gelatin microspheres loaded with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), namely meloxicam (MXM), integrated into a gelatin scaffold. This system is designed to enhance drug delivery efficiency and sustain drug release. Methods: MXM-loaded microspheres with a 1:1 ratio of Poly Lactic Acid (PLA) and Poly Lacto Glycolic Acid (PLGA) were optimized for size, yield, efficiency, and release. Gelatin scaffolds were designed as rod-shaped implants, tested for stability and degradation in pH 7.4 and pH 4.0 buffers at 37 °C for 100 d, and sterilized with γ-radiation. Implants were evaluated in rabbits, with blood samples analyzed via High-Performance Liquid Chromatography (HPLC) for pharmacokinetic parameters statistically analyzed (P<0.05). Results: The microspheres with a 1:1 ratio of PLA and PLGA demonstrated favorable characteristics such as smaller particle sizes, high yield, and efficient drug entrapment and release. Optimization using Design Expert resulted in highly desirable scaffolds, evidenced by a desirability factor close to one across all assessed variables. The scaffolds exhibited robust physicochemical properties, including sustained drug release over an extended period, highlighting their potential for diverse biomedical applications. Implants showed greater stability in pH 7.4 buffer solutions in contrast to pH 4.0 over 100 d, with higher mass loss in acidic environments (14.4% vs. 9.66%). γ-Radiation sterilization effectively prevented microbial contamination. In vivo studies confirmed MXM detection in plasma, with Scaffold-MXM microspheres (iS-MMS-17) (optimized implantable scaffold) showing higher mean Cmax values and significant Area Under Curve (AUC) parameters, suggesting its potential for effective therapy. Conclusion: The study found that the scaffolds exhibited strong physicochemical properties and sustained drug release, making them suitable for biomedical use. Implants were more stable at pH 7.4 than at pH 4.0, and γ-radiation effectively prevented microbial contamination. In vivo studies confirmed MXM detection, with iS-MMS-17 showing promising pharmacokinetic parameters for pain and arthritis therapy.

A mamografia por Raios X tem apresentado alta sensibilidade na detecção de lesões de mama, porém a mesma tem se mostrado limitada na tarefa de diagnóstico diferencial. Muitos especialistas em câncer de mama crêem na necessidade de uma ferramenta de diagnóstico por imagem mais específica, uma vez que, da estimativa de 700.000 biópsias de mama feitas anualmente nos Estados Unidos, somente 1 em 4 apresenta achado de câncer. Outras técnicas de imagens estão sendo pesquisadas e, pelos resultados apresentados, poderão, em breve, assumir papel importante na detecção de lesões de mama em pacientes assintomáticos. Dentre essas novas técnicas destacamos a cintilografia mamária marcada com MIBI-99mTc. Neste trabalho, são descritos os aspectos técnicos desse novo exame, realizado segundo a técnica proposta por Khalkhali11 e são apresentados os resultados de vários estudos publicados nos últimos anos.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Breast cancer represents the most frequently diagnosed form of cancer among women on a global scale. In recent years, there has been a notable increase in interest among researchers in exploring alternative therapeutic methods, including stem cell therapy. The objective of this study was to examine the impact of adipose-derived mesenchymal stem cell-conditioned media (AD-MSCs-CM) on apoptosis induction and migration inhibition of breast cancer cells (MDA-MB-231) in vitro. In this study, malignant breast cancer cells (MDA-MB-231) and adipose-derived mesenchymal stem cells (AD-MSCs) were cultured separately in DMEM/F12/FBS (15%) culture media under standard conditions. Subsequently, the conditioned media derived from AD-MSCs was introduced to the MDA-MB-231 cells. Following a 24-and 48-hour exposure period, the expression levels of CASP3, KRAS, and MMP9 were evaluated using a quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. Furthermore, the proliferation and migration abilities of the cancer cells were evaluated using MTT and wound healing assays, respectively. Furthermore, the protein expression of Caspase-3, K-RAS, and MMP-9 was examined using a western blot assay. It is noteworthy that the expression levels of the MMP9 and KRAS genes were significantly reduced following treatment with AD-MSCs-CM in MDA-MB-231 cells. Furthermore, the CASP3 gene expression level was found to have increased significantly in the treated groups. Additionally, the proliferation of MDA-MB-231 cells treated with AD-MSCs-CM was markedly diminished by MTT and wound healing assays. Moreover, the AD-MSCs-CM was observed to induce caspase-3 activation and reduce the protein expression of K-RAS and MMP-9. The results of this study indicate that AD-MSCs-CM may exert an influence on the apoptosis, proliferation, and migration of breast cancer cells. Consequently, it could be proposed as a promising therapeutic strategy for the suppression of breast cancer. However, further testing and research are required to validate these findings and to ascertain the full potential of this approach.

Arsenic is a naturally occurring element in earth crust which is known to be heavy metals that is a very harmful environmental pollutant that has a strong link towards human health. Arsenic may cause gene mutation, alterations, cognitive disorders and malignancy in a person, even causing infertility when it gets consumed either unknowingly when it comes to pollution debris or deliberately in case of homicidal. Arsenic is one of those heavy metal which can be able to cross blood brain barrier and directly affects the central nervous system and also infants in case of pregnant lady therefore, its detection at nano level becomes so important. A vast range of biosensors for qualitative and quantitative classification and recognition of arsenic have been developed over the last few decades. Biosensors are analytical instruments with great specificity, accessibility, relatively low consumption and convenience of being used that can be used to monitor an aspect of diverse analytes qualitatively and quantitatively. Because of its widespread presence in nature and substantial toxicity to living organisms, arsenic must be evaluated often in groundwater, sediment, agricultural and dietary samples. The purpose of this review is to highlight some recent advances in biosensor development by focusing on recombinant entire cells or specific arsenic-binding nucleotide sequences and peptide. Surface plasmon resonance recombinant technology, reusable enzymatic strips for onthe-spot detection have also been proposed as future technologies.

Uc boyutlu yazicilar gunumuzde bircok yerde kullanilan hizla gelisen bir teknolojidir. Bu arastirmada, gunumuzde siklikla kullanilan uc boyutlu yazicilarin saglik alanindaki gelismelerini inceledik. Uc boyutlu (3D) bioprint, doku anatomi, biyoloji ve fizyolojiyi canlandirmak icin canli hucreler, nukleik asitler, ilac partikulleri, proteinler ve buyume faktorleri dahil, biyolojik materyallerin tasarimi ve tam yerlesimi icin guclu bir arac haline gelmistir. Bioprinting son on yilda onemli olcude gelismistir ve gelecekte canli doku uretiminde yaygin olarak kullanilacaktir. Cogu hasta, gelisen teknoloji sayesinde doku hasari ve organ nakli sorunlarinin, ozellestirilmis modeller ile uc boyutlu biyo-baskilarla cozulecegini dusunmektedir. Bu calismada uc boyutlu biyo-yazici teknolojisi tanitildi, doku muhendisligi, rejeneratif tip vb. Saglik alaninda uygulamalar ve kullanimlari incelenmistir.

Purpose To investigate the therapeutic potential of extracellular vesicles (EVs) derived from human nucleus pulposus cells (NPCs), with a specific emphasis on Tie2-enhanced NPCs, compared to EVs derived from human bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a coccygeal intervertebral disc degeneration (IDD) rat model. Methods EVs were isolated from healthy human NPCs cultured under standard (NPC STD -EVs) and Tie2-enhancing (NPC Tie2+ -EVs) conditions. EVs were characterized, and their potential was assessed in vitro on degenerative NPCs in terms of cell proliferation and senescence, with or without 10 ng/mL interleukin (IL)-1β. Thereafter, 16 Sprague-Dawley rats underwent annular puncture of three contiguous coccygeal discs to develop IDD. Phosphate-buffered saline, NPC STD -EVs, NPC Tie2+ -EVs, or BM-MSC-derived EVs were injected into injured discs, and animals were followed for 12 weeks until sacrifice. Behavioral tests, radiographic disc height index (DHI) measurements, evaluation of pain biomarkers, and histological analyses were performed to assess the outcomes of injected EVs. Results NPC-derived EVs exhibited the typical exosomal morphology and were efficiently internalized by degenerative NPCs, enhancing cell proliferation, and reducing senescence. In vivo, a single injection of NPC-derived EVs preserved DHI, attenuated degenerative changes, and notably reduced mechanical hypersensitivity. MSC-derived EVs showed marginal improvements over sham controls across all measured outcomes. Conclusion Our results underscore the regenerative potential of young NPC-derived EVs, particularly NPC Tie2+ -EVs, surpassing MSC-derived counterparts. These findings raise questions about the validity of MSCs as both EV sources and cellular therapeutics against IDD. The study emphasizes the critical influence of cell type, source, and culture conditions in EV-based therapeutics.

El desarrollo de la investigación científica pone de manifiesto la relevancia que tiene la ética a la hora de diseñar y aprobar protocolos de investigación. A los desafíos tradicionales, se suma el impacto de la globalización en lo que se refiere a aspectos culturales que deben ser tomados en cuenta (por ejemplo, en el consentimiento informado y el asentimiento informado en menores de edad), pero fundamentalmente respecto de lo moralmente permisible en experimentación, que se ha focalizado por tradición, en lo relacionado con el cumplimiento o no de normas y pautas internacionalmente aceptadas, mas no en la evaluación y categorización del daño infligido como consecuencia de la investigación. Es imposible desconocer los aportes que H. K. Beecher realizó a la farmacología clínica, especialmente en el abordaje del dolor y a la ética médica especialmente en la forma en que se produce el conocimiento científico. Estos aportes produjeron cambios en la metodología de la investigación, prom...

Clonación de embriones: ¿Una nueva esperanza terapéutica por Rubén P. Laguens* Recibido: 26 febrero de 2004 Aceptado: 20 marzo de 2004 Cuando leemos CLON, o pensamos en esa palabra, vienen a nuestra mente imágenes de bacterias, o de células genéticamente uniformes, descendientes de un progenitor único, y si pensamos en mamíferos, la oveja Dolly, o nuestra ternera Pampa y sus hermanas, aparecen como el paradigma de un animal clonado. Si bien es posible desarrollar humanos clonados, y sería tentador crear razas de genios o de superhombres, no es necesario tener alguna creencia

BackgroundMultimodality treatment for head and neck cancer leads to substantial functional and esthetic impairment mainly manifested as radiation‐induced skin fibrosis (RIF) in combination with volumetric defects and reduction in neck mobility. This study assessed the impact of lipotransfer as part of secondary surgical procedure(s) in patients treated for head and neck malignancies.MethodsRetrospective analysis was performed between 2005 and 2016. All patients with a history of head and neck malignancy, multimodal treatment including at least surgery or radiotherapy, and at least 2‐year disease‐free survival were included. Thirty‐eight patients (22 men, 16 women) matched the inclusion criteria.ResultsThirty seven (97%) reported esthetic and functional improvements in their RIF and volumetric defect at follow‐up of 32 months. Major improvement in esthetic and functional outcome was reported by 24 (63%) patients and surgeons and minor by 13 patients and surgeons (34%) without causing...

Polycythemia Vera (PV) is a blood disorders known as myeloproliferative disease. Gastric and duodenal ulcer is a frequent disease among population but rarely is a complication of myeloproliferative disorders. Its main etiologies are inbalance of gastric acid secretion and mucosa protection. The complication of PV by an ulcer is a possible but not scientifically well established. The microvascular complications by thrombosis which lead to mucosa alteration are highly suspected. The treatment of gastric ulcer is medical using proton pomp inhibitors but also surgery for perforated ulcer while the phlebotomy is for the PV in emergency to reduce the symptoms and prevent vascular complications.

Работа посвящена изучению механического поведения материала на основе полимолочной кислоты (ПМК), изготовленного методом моделирования наплавления. Влияние мезоструктуры на макромасштабные механические свойства материала характеризовали степенью пористости. Экспериментально установлена зависимость продольных и поперечных механических свойств от пористости. Показано, что в силу кристаллизации после плавления и экструдирования свойства одиночного волокна из ПМК со временем возрастают. Полученные результаты показывают, что классическая теория слоистых композитов и критерий разрушения Цая–Хилла позволяют предсказать модуль упругости и прочность материалов из ПМК, изготовленных с помощью 3D печати.

Recent studies indicate that anti-inflammatory drugs, act as a double-edged sword, not only exacerbating secondary brain injury but also contributing to neurological recovery after stroke. Our aim is to explore whether there is a beneficial role for neuroprotection and functional recovery using anti-inflammatory drug along with neurorehabilitation therapy using transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), so as to improve functional recovery after ischemic stroke. We develop a computational systems biology approach from preclinical data, using ordinary differential equations, to study the behavior of both phenotypes of microglia, such as M1 type (pro-inflammatory) vis-à-vis M2 type (anti-inflammatory) under anti-inflammatory drug action (minocycline). We explore whether pharmacological treatment along with cerebral stimulation using tDCS and rTMS is beneficial or not. We utilize the systems pathway analysis of minocycline in...

Preclinical transplantations using human neuroepithelial stem (NES) cells in spinal cord injury models have exhibited promising results and demonstrated cell integration and functional improvement in transplanted animals. Previous studies have relied on the generation of research grade cell lines in continuous culture. Using fresh cells presents logistic hurdles for clinical transition regarding time and resources for maintaining high quality standards. In this study, we generated a good manufacturing practice (GMP) compliant human iPS cell line in GMP clean rooms alongside a research grade iPS cell line which was produced using standardized protocols with GMP compliant chemicals. These two iPS cell lines were differentiated into human NES cells, from which six batches of cell therapy doses were produced. The doses were cryopreserved, thawed on demand and grafted in a rat spinal cord injury model. Our findings demonstrate that NES cells can be directly grafted post-thaw with high cell viability, maintaining their cell identity and differentiation capacity. This opens the possibility of manufacturing off-the-shelf cell therapy products. Moreover, our manufacturing process yields stable cell doses with minimal batch-to-batch variability, characterized by consistent expression of identity markers as well as similar viability of cells across the two iPS cell lines. These cryopreserved cell doses exhibit sustained viability, functionality, and quality for at least 2 years. Our results provide proof of concept that cryopreserved NES cells present a viable alternative to transplanting freshly cultured cells in future cell therapies and exemplify a platform from which cell formulation can be optimized and facilitate the transition to clinical trials.

After Paolo Macchiarini's star fell in Sweden, the Italian surgeon still had a place to shine: Russia. The Karolinska Institute (KI) in Stockholm fired him in March 2016 for multiple ethical violations, including "breach of KI's fundamental values" and "scientific negligence." But Russia had long showered Macchiarini with funding and opportunities to perform his experimental surgeries to implant artificial tracheas, and it allowed him to stay. Now, a year later, his Russian refuge has ended as well.

Vibrational Regenerative Medicine (VRM) is an integrative health approach that combines scientific principles, energy medicine, and holistic healing practices. Emphasizing the interconnectedness of body, mind, and spirit, VRM employs vibrational frequencies and natural thermal water therapy to promote healing and overall well-being. This paper explores foundational concepts of VRM, including the chakra system, the Med Bed technology, and the proposed integrative processes that facilitate regeneration and recovery. Furthermore, the discussion highlights the importance of safeguarding the intellectual property associated with VRM innovations.

Metallic materials composed of alternating soft and hard phases can be tailored for desirable strength-ductility combinations. In this work, (AlNi) x (FeCr) 100-x (x = 40, 50 and 60) A2-B2 dual-phase medium-entropy alloys (MEAs) fabricated using an arc-melting furnace were studied. Fractions and morphologies of (Fe, Cr)-rich A2 and (Al, Ni)-rich B2 phases in the alloys were modified by simply adjusting the ratio of (AlNi) to (FeCr), based on phase diagrams calculated using Thermo-Calc software. The (AlNi) x (FeCr) 100-x alloys showed different microstructural features, including interdendritic regions with irregular A2-B2 lamellae (in all three alloys), and dendrite cores with different morphologies such as A2 matrix embedded with B2 particles (x = 40), A2-B2 weave-like structure (x = 50), and B2 matrix embedded with A2 nanoparticles (x = 60). Based on microindentation tests, all the core zones showed higher hardness than interdendritic regions, benefiting from their weave-like or particle-dispersed microstructure. Compressive tests and EBSD analyses indicated that the presence of the core zone having a structure of B2 matrix embedded with A2 nanoparticles was particularly effective for enhancing the strain-hardening capacity and wear resistance. This study demonstrates a simple way, via directly adjusting the fraction ratio of (AlNi) to (FeCr), to control the heterogeneous structure of this MEA system for desirable properties, which can be extended to other A2-B2 dual-phase multi-principal element alloy systems.