Stem cell and Regenerative medicine

An amputated limb of an adult urodele amphibian is capable of undergoing regeneration. The new structures form from an undifferentiated mass of cells called the regenerative blastema. The cells of the blastema are believed to 1968). However, such experiments, relying on radioac-

The visual impairment associated with inherited retinal degeneration and age-related degeneration of photoreceptors is causing substantial challenges in finding effective therapies. However, induced pluripotent stem cell (iPSC)-derived therapeutic cells such as photoreceptor and retinal pigment epithelium (RPE) cells provide the ultimate options in the rescue of lost photoreceptors to improve the visual function in end-stage degeneration. Retinal cells derived from iPSC are therapeutic cells that could be promising in the field of cell replacement therapy and regenerative medicine. This review presents an overview of the photoreceptor degeneration, methods of iPSC generation, iPSC in retinal disease modeling, summarizes the photoreceptor differentiation protocols, and challenges remained with photoreceptor cell replacement for the treatment of retinal diseases. Thus, the burden and increased incidence of visual impairment emphasizes the need of novel therapy, where iPSC-derived photoreceptor and RPE cells proved to be promising for curing the retinal dysfunction and act as renovation in approach to improve visual function.

Human induced pluripotent stem cell (hiPSC)-derived three-dimensional retinal organoids are a new platform for studying the organoidogenesis. However, recurrent genomic aberration, acquired during generation of hiPSCs, limit its biomedical application and/or aberrant hiPSCs has not been evaluated for generation of differentiated derivatives, such as organoids and retinal pigment epithelium (RPE). In this study, we efficiently differentiated mosaic hiPSCs into retinal organoids containing mature photoreceptors. The feeder-free hiPSCs were generated from the human epidermal keratinocytes that were rapid in process with improved efficiency over several passages and maintained pluripotency. But, hiPSCs were cytogenetically mosaic with normal and abnormal karyotypes, while copy number variation analysis revealed the loss of chromosome 8q. Despite this abnormality, the stepwise differentiation of hiPSCs to form retinal organoids was autonomous and led to neuronal lamination. Furthermore, the use of a Notch inhibitor, DAPT, at an early timepoint from days 29-42 of culture improved the specification of the retinal neuron and the use of retinoic acid at days 70-120 led to the maturation of photoreceptors. hiPSC-derived retinal organoids acquired all subtypes of photoreceptors, such as RHODOPSIN, B-OPSIN and R/G-OPSIN. Additionally, the advanced maturation of photoreceptors was observed, revealing the development of specific sensory cilia and the formation of the outer-segment disc. This report is the first to show that hiPSCs with abnormal chromosomal content are permissive to the generation of three-dimensional retinal organoids.

The objective of this article is to highlight the advantages of human reproduction from the standpoint of a physiological process, a natural cycle of human fertilization, compared to the changes induced artifi cially in an assisted fertilization cycle, by underscoring the basic differences in human reproduction and in cell biology. It is well known that maturation of the gametes in natural fertilization requires the integrity of spermiogenesis in the male and ovogenesis in the female. These two processes make it possible to obtain a mature cell for fertilization based on the presence of germ cells from both the man and the woman, which must migrate to the ovary and to the testicle where they multiply through mitosis and then, through chromosome reduction, are provided with the mature haploid gametes to be fertilized. At the gonad level, the ovaries produce sexual steroids that are intrinsically related to follicular maturity and growth of the endometrium, basic situations that are n...

Shinya Yamanaka and Sir John Gurdon were awarded the Nobel Prize in Physiology or Medicine for their pioneering research into the reprogramming of mature cells into a pluripotent state. The technology developed by Yamanaka and colleagues allows researchers to turn terminally differentiated somatic cells back into a stem-cell state. 1 These induced pluripotent stem cells (iPSCs) can be cultured indefinitely in the laboratory, and can undergo directed differentiation into any cell type of interest. This is highly beneficial for disease-modelling studies, since researchers are able to culture cells that are not normally obtainable, such as neurons or retinal cells. Furthermore, the differentiated cells can be used to test potential therapies in patient-derived cells, and may even be used for future therapeutic cell transplantation. iPSC research is no longer a 'foreign' technology, with laboratories from at least two South African institutions employing these methods for 'disease-in-a-dish' modelling. Given the seemingly endless possibilities for future iPSC-based research, we wish to highlight the challenges associated with obtaining comprehensive informed consent from research participants. A recent review from the National Institutes of Health in the USA outlined the standards, policies, protocols and regulations required for cell-based therapies, and addressed specimen collection for iPSC research. The authors pointed out that providing accurate information about what will not be done with a research participant's specimen is almost impossible, given the rapid advances in research. We propose that the informed consent documentation must be explicit when addressing these matters. In South Africa, for example, definitive assurance could be given that germline cell derivatives and reproductive applications will not be attempted or developed with the generated iPSCs, as current legislation prohibits certain uses of biological samples, such as the reproductive cloning of humans (National Health Act 61/2003: 57(1)). These assurances will need to be reviewed regularly, however, so that research possibilities are not stultified by bureaucracy and avoidance of debate. In many respects, iPSC research seems to provide more questions than answers and this creates a new challenge for researchers and research ethics committees. 3 A balance must be found between consent that is too broad and indistinct, or too narrow, which may hinder future research prospects. Some commentators favour a 'tiered' approach to consent, which allows participants to consent to specific uses, and to stipulate their wishes regarding banking and sharing their biological material with other researchers, and whether they wish to be re-contacted in the event that further use of their samples is needed. This would enable individuals to opt out of sensitive areas such as gamete formation, reproductive research, commercialisation and genetic manipulation. In the South African context, we need to determine efficacy and safety by using iPSCs as pre-clinical cellular models, in preparation for future therapeutic development and human clinical trials. By addressing the scientific, legal and ethical implications of establishing and using iPSCs in the laboratory, we can use this time constructively and productively to develop prospective policies for the use of iPSCs in future therapeutic applications.

As Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are easily accessible, easy to isolate, and ethically acceptable, they represent a promising source of MSCs for use in regenerative medicine. Considering decisions on WJ-MSCs collection requires extensive knowledge of the factors that impact their yield. This study's aim was to evaluate the influence of parameters related to mothers and newborns on the WJ-MSCs yield. The WJ-MSCs were isolated and expanded after being isolated from 79 umbilical cord (UC) samples. Population doubling time and cell proliferation were assessed. By flow cytometry analysis, WJ-MSCs were identified by positivity of CD105, CD90, and CD73 and negativity of CD45 and CD34. There was a statistically significant negative correlation between UC width and P1 doubling time. Maternal age and WJ-MSC yield were shown to be negatively correlated. Birth weight and gestational age showed a significant positive correlation between WJ-MSCs yield and neonatal variables. No significant correlations were detected between the WJ-MSCs and the mother parity, nor the neonatal sex, fetal presentation, or head circumference. The WJ-MSCs yield increases with younger maternal age, higher gestational age, and increased neonatal birth weight. Hence, consideration should be given to these factors when selecting the ideal donors.

Tissue engineering has revolutionized regenerative medicine by enabling the development of functional tissues and organs. However, challenges such as designing complex threedimensional (3D) structures and optimizing biomaterials remain significant. Artificial intelligence (AI) has emerged as a transformative tool in tissue engineering, offering solutions in computational modeling, biomaterial design, cell culture optimization, and personalized medicine. Smart biomaterials, which dynamically interact with biological environments, further enhance tissue integration and therapeutic efficacy. AI-driven predictive modeling accelerates biomaterial development by optimizing compositions, improving bioink formulations, and reducing experimental costs. Despite its promise, AI integration in biomaterials research faces challenges, including ethical concerns, data limitations, and the interpretability of models. Addressing these issues through data standardization, collaboration, and explainable AI will be crucial for advancing AI-assisted tissue engineering. This synergy between AI and biomaterials holds great potential for personalized and efficient regenerative therapies. This communication delineates the role of artificial intelligence in tissue engineering, smart biomaterials and predictive modeling for regenerative medicine.

Cardiomyocytes (CM) in the adult mammalian heart have limited capacity to proliferate following injury. Thus, therapies to induce endogenous regeneration of the heart would significantly improve cardiac function in the setting of heart disease. We have previously engineered 3-dimensional cylindrical tissues ("cardiobundles") made from neonatal rat CM embedded in fibrin-based hydrogel (∼16 cardiobundles derived from 1 neonatal heart), which accurately mimic the dense and anisotropic cellular structure of native myocardium while also displaying tissue-level functional properties comparable to the adult or adolescent heart [1]. Here, we show that CM in cardiobundles stop proliferating (<1% turnover per day) after 2 weeks in standard culture conditions, representing a high-fidelity in vitro model to test potential therapies for re-activation of the cell cycle in post-mitotic myocardium. Furthermore, we establish various injury methods (e.g., cardiotoxin, hydrogen peroxide, calcium ionophores) that result in CM death and a 60-80% decline in the cardiobundles' active contractile force, enabling studies of CM regeneration and functional recovery after cardiac injury. Electrical stimulation of injured cardiobundles results in partial yet incomplete regeneration and recovery of contractile force. The cardiobundle injury model is thus a realistic 3-D system to test new small molecule and gene therapies targeting CM regeneration in the terminally differentiated heart, with higher throughput than in vivo studies on the intact heart.

It is estimated that 10-40% of post-menopausal women experience local symptoms related to vaginal atrophy; current treatments focus on symptom management. To mitigate these degenerative changes and associated symptoms, patients may benefit from novel treatment involving adipose-derived mesenchymal stem cells, both as a native tissue bulking agent and for the regenerative, trophic environment stimulated by these cells. This case reports details the first known case of treatment for atrophic vaginitis with mesenchymal stem cells, with promising early and late improvement in symptoms (dryness, dyspareunia). Cell-based and regenerative medicine therapies represent promising novel treatments for atrophic vaginitis and additional studies are warranted to determine clinical efficacy and long-term effect.

This document proposes a novel convergence between Viscous Time Theory (VTT) and modern stem cell research, positioning informational coherence as a critical variable in cellular regeneration. While traditional regenerative medicine focuses on biochemical and genetic pathways, VTT introduces a dynamic framework in which biological states are modulated by localized informational density, viscosity, and temporal coherence. We present here a theoretical foundation, updated scientific context, a mathematical model, and a proposed protocol for future experimentation in coherence-based stem cell therapy.

Sports injuries and secondary joint problems, mainly of the knee, are common, especially in sports associated with high impact activities and/or torsional loading. The consequences can be career ending in elite athletes and reduce exercise activities in recreational people. Various cell products can be injected intra-articularly. First, fresh cellular mixtures can be prepared and injected in the same day, such as stromal vascular fraction of adipose tissue (SVF) and bone marrow concentrates (BMCs). Second, autologous mesenchymal stromal cells (MSCs) can be isolated from BMCs or SVF and, after several weeks of laboratory expansion, several millions of MSCs can be obtained for intra-articular injection. Finally, allogeneic MSCs from the bone marrow, adipose tissue or perinatal tissues of selected donors constitute an ‘off-the-shelf’ experimental treatment for injection delivery in patients with osteoarthritis of the knee. The perceived efficacy of all these products is based on the hy...

The Ace Pico Protocol, developed by ACE Cells Lab Limited,
U.K., presents a novel approach to cellular therapy by
mechanically dissociating stem cells into nanoscale
fragments (5-20 nm, as confirmed by Electron Microscopy
[EM] at 92,000x magnification) for sublingual delivery,
aiming to overcome the challenges associated with multidosing
in regenerative medicine. Multi-dosing, essential due
to the short half-life of bioactive peptides and limited in vivo
stem cell proliferation, often leads to immune reactions,
patient discomfort, and increased costs. This study evaluates
the protocol’s efficacy and safety through EM, UV-Vis
spectrophotometry, and animal safety tests, comparing it to
traditional methods. EM analysis of sheep brain cells
revealed polydisperse fragments ideal for mucosal
absorption (<200 nm), while UV-Vis spectrophotometry of
human placenta samples showed preserved nucleic acids
and proteins (peaks at 227.5-240 nm, >3 A) and pigments
(405.5-573.5 nm), indicating bioactivity retention via a cold
(<10°C) mechanical process. Animal safety tests (2000 mg/
kg, sublingual) on albino rats showed no toxicity, with minor
physiological changes (e.g., increased water consumption
and liver weight for brain extracts, decreased spleen weight
for kidney extracts), supporting safety. A plasma protein
study in mice across five administration routes
(intramuscular, intravenous, subcutaneous, topical,
sublingual) demonstrated significant increases postadministration
(p<0.01), with sublingual delivery yielding the
highest mean increase (0.66 g/dL), correlating with efficient
absorption of nanoscale fragments. Compared to
nanoparticle carriers, exosomes, and peptide therapies, the
Ace Pico Protocol offers a superior single-dose, non-invasive
delivery method with a comprehensive \"whole cell \"
payload, reducing multi-dosing needs. However, high UV
absorbance suggests potential scattering from undissolved
particles, indicating a need for filtration optimization. These
findings support the protocol’s potential to enhance
therapeutic efficacy and accessibility, warranting further
studies for refinement and long-term effects.
Keywords: Ace pico protocol; Cellular therapy; Stem cell
applications; Multi-dosing challenges; Regenerative medicine;
Nanoscale fragments; Sublingual delivery

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

Alcalá Pérez D y cols. Enfermedad injerto contra huésped 74 74 74 74 74 edigraphic.com * Jefe del Servicio de Dermatología Pediátrica, Centro Dermatológico Pascua (CDP). ** Residente de 3er año Dermatología, CDP. *** Residente de 4º año Dermatología, CDP.

The repair of critical-sized bone defects, resulting from tumor resection, skeletal trauma or infection, remains a significant clinical problem. A potential solution is a tissue-engineered approach that utilises the combination of human mesenchymal stem cells (hMSCs) with synthetic biomaterial scaffolds, mimicking many of the biochemical and biophysical cues present within the native bone. Unfortunately, osteocyte cells, the orchestrators of bone maturation and homeostasis, are rarely produced within such MSC-seeded scaffolds, limiting the formation of true mature cortical bone from these synthetic implants. In this contribution, a bone morphogenic protein-6 (BMP6)-presenting osteon-like scaffolds based on electrospun poly(lactic-co-glycolic acid) (PLGA) fibrous scaffolds and poly(ethylene glycol) (PEG) based-hydrogels is reported. BMP6 peptide is shown to drive higher levels of SMAD signalling than the full-length protein counterpart. Osteon-mimetic scaffolds promoted the formation...

In ink-jet printing, droplets of ink are generated using thermal or piezoelectric actuators at a close distance above the target surface, typically 0.5-2 mm. Commonly used droplet volumes range from a few pL to over 100 pL, with up to about 1 nL in a few instances. The ink may represent the bulk material to be dispensed and accumulated in the target structure (e.g., microlenses), or the fluid component of a solution or suspension may serve only as a carrier for the material of interest (display phosphors, conducting powders, medical reagents).

Objective: This article presents the case of a female patient with Alzheimer's disease (AD). The patient was treated with cholinesterase inhibitors and also with intravenous administration of autologous adipose stem cells. Methods: The patient was assessed with a neuropsychological battery including measures of general cognition, functional problems, neuropsychiatric issues, memory (verbal, visual and episodic), verbal learning and visuospatial abilities. Magnetic resonance imaging (MRI) scans were conducted before and after the treatment with stem cells. Results: A transient and mild improvement of scores in measures of general cognition and neuropsychiatric issues was evident. A rapid deterioration followed the initial improvement. The first MRI scan showed ischemic areas in periventricular white matter of both hemispheres, as well as in both temporal and parietal lobes. The second MRI scan revealed the same picture with no significant changes. Conclusion: This case report indicates that the administration of stem cells is feasible in a clinical setting however its effectiveness in the treatment of AD is uncertain. The improvement of the patient's condition highlights the potential therapeutic action of stem cells, however the rapid deterioration poses questions concerning limited effectiveness or possible side effects of stem cell administration. Further research is needed in order to clarify the method's effectiveness.

Wraz z rozwojem cywilizacyjnym i związaną z tym rosnącą długością życia zwiększa się liczba osób zapadających na choroby nowotworowe. Postępy w rozwoju biologii i medycyny powodują, że skuteczność leczenia nowotworów jest o wiele wyższa; niestety postęp ten w większości dotyczy krajów wysoko rozwiniętych. Zważywszy, że naukowcy badający procesy biologiczne w większości posługują się modelami badawczymi, w tym zwierzęcymi, dobór takiego modelu ze względu na jego odpowiedniość w stosunku do stawianych problemów badawczych, a także uwarunkowania ekonomiczne i etyczne jest niezwykle ważny. Na przestrzeni ostatniej dekady nastąpił gwałtowny wzrost popularności ryby danio pręgowanego jako organizmu modelowego w wielu dziedzinach badań biologicznych i biomedycznych. Poniższy artykuł przedstawia skrótowo możliwości zastosowania danio pręgowanego jako modelu badawczego w badaniach nad biologią nowotworów.

Social and economic development contribute to the increase in human lifespan. This, unfortunately, results in increased incidence of cancer. Progress in biomedical research significantly increased survival rates in cancer patients, but this increase is largely limited to more developed countries. Given that biologists usually work with research models, including model animals, the choice of the model with regard to its relevance and economic and ethical ramifications becomes crucial. Within the last decade rapid increase in popularity of zebrafish as a model animal in biomedical research occurred. The following article delineates current uses and opportunities that zebrafish presents in the field of cancer research. DANIO PRĘGOWANY JAKO ORGANIZM MODELOWY W BADANIACH NAD NOWOTWORAMI Maciej Olszewski i Magdalena Pruszko (Warszawa) Choroby nowotworowe jako problem społeczny i medyczny Choroby nowotworowe nazywane są chorobami cywilizacyjnymi i często wzrost zachorowalności na nie kojar...

Benign Prostatic Hypertrophy (BPH) is the most common benign urological condition in males. It is a progressive condition associated with aging, affecting over 80% by age 80 and can affect quality of life. While the exact cause is not fully known, hormones, metabolic alterations, inflammation and vascular flow may be contributing causes of BPH. Medical or surgical treatments are the standard of care for addressing associated Lower Urinary Tract Symptoms (LTUS) and erectile dysfunction associated with BPH, but each has risks and is not always effective. Pulsed Electromagnetic Field (PEMF) therapy is a noninvasive modality that has been shown to address some of the potential underlying contributing factors of BPH, including inflammation and microvascularity. Ultrasound has been shown to be an effective modality to evaluate inflammatory and microvascular changes in the prostate in addition to size. Here we present three case studies of males with known BPH and varying degrees of LTUS treated with PEMF for 30 days, utilizing ultrasound to evaluate response. Prostate size decreased in all participants, with average decrease of 27.3% and no adverse effects.

This field is built by combining multiple elements, including living cells, a supporting matrix (i.e., a scaffold), and cellular communicators (or signaling systems) that stimulate cells and their environment to grow and develop into new tissues or organs. Indeed, regenerative medicine is an emerging multidisciplinary field involving biology, medicine (human and veterinary), and engineering, and is likely to revolutionize how we improve the health and quality of life of millions of patients worldwide, regardless of species, by restoring, maintaining, or improving tissue and organ function.

Innovative Applications of 3D Printing and Regenerative Medicine in Reconstructive Plastic Surgery

The integration of 3D printing and regenerative medicine has reshaped modern reconstructive plastic surgery. Three-dimensional printing allows for patient-specific implants and surgical planning models, enhancing anatomical precision and functional outcomes. Concurrently, stem cell-enriched fat grafting (Cell-Assisted Lipotransfer) promotes vascularization, tissue regeneration, and improved aesthetic results. The synergistic application of these technologies offers a powerful, personalized approach to complex reconstructions, despite current challenges in cost, accessibility, and ethical considerations. This paper presents the biological basis, clinical applications, protocols, and future directions of these innovations, highlighting their transformative impact on surgical practice.

Bioreactor systems that use a new aeration concept have recently been introduced. Bioreactors can assist in the development of new tissues in vitro by providing appropriate stimuli to the cell cultures. The design of bioreactors for tissue engineering is very complex and is often tailored to individual cell-engineered-tissue products. Critical elements in bioreactor systems based on cells and scaffolds include cell seeding, the nutrient and gas supply to cells, and mechanical stimuli. Flow perfusion systems have been shown to enhance cell growth, differentiation, and tissue formation as well as provide for the appropriate and necessary mass transfer of nutrients, gases, metabolites, and regulatory molecules. The beneficial effects of fluid flow induced convective transport and shear stress have been exploited in various types of bioreactors because fluid flow-through cell and tissue engineered constructs increase nutrient transport. These systems are called flow-perfusion bioreactors. In this paper, we review the characteristics of bioreactor systems used for cell culture in tissue engineering, and provide a schematic design for a novel bioreactor system that incorporates the elements we deem critical for such systems.

Bioreactor systems that use a new aeration concept have recently been introduced. Bioreactors can assist in the development of new tissues in vitro by providing appropriate stimuli to the cell cultures. The design of bioreactors for tissue engineering is very complex and is often tailored to individual cell- engineered-tissue products. Critical elements in bioreactor systems based on cells and scaffolds include cell seeding, the nutrient and gas supply to cells, and mechanical stimuli. Flow perfusion systems have been shown to enhance cell growth, differentiation, and tissue formation as well as provide for the appropriate and necessary mass transfer of nutrients, gases, metabolites, and regulatory molecules. The beneficial effects of fluid flow induced convective transport and shear stress have been exploited in various types of bioreactors because fluid flow-through cell and tissue engineered constructs increase nutrient transport. These systems are called flow-perfusion bioreacto...

Hemophilia B, a recessive X-linked bleeding disorder, arises from vitamin K-dependent coagulation factor IX (FIX) deficiency. Despite using FIX activity levels to gauge disease severity, they often do not align with the bleeding phenotype due to complex regulatory processes in coagulation. With rapid advancements in gene therapy and the availability of long-acting medications, the treatment landscape for hemophilia B is evolving rapidly. Understanding the factors influencing hemostatic and clinical outcomes and therapeutic responses is crucial in this era of progress. Unlike factor VIII (FVIII), FIX pathways' synthesis, cellular interactions, and clearance mechanisms remain less studied. Significant aspects include the roles of vascular collagen in platelet adhesion at hemostatic sites and magnesium's dual impact on FIX activation and platelet function. Enhanced comprehension of these mechanisms through biochemical and translational research promises to develop relevant diagnostic tests that assess treatment efficacy and hemostasis. In contemporary hemophilia care, personalized treatment strategies tailored to individual patient needs are increasingly vital. This review underscores the importance of advancing our understanding of hemophilia B's biological intricacies to facilitate the development of more effective and economical therapies.

The potential application of extracellular vesicles (EVs) in regenerative and personalized medicine has attracted substantial interest in recent years, highlighting the need for standardized protocols for their administration in preclinical and clinical settings. EVs, which play critical roles in intercellular communication and have significant therapeutic potential, have prompted extensive research and advancements in their clinical applications. However, the rapid evolution of this field has also revealed variability in how EVs are isolated, characterized, and used across different studies. Over the past decade, organizations such as the International Society for Extracellular Vesicles (ISEV) and the International Society for Cell and Gene Therapy (ISCT) have actively worked to address these challenges by proposing frameworks for standardizing EV-related research. As the clinical evaluation of therapeutic EVs becomes increasingly commonplace, there is a need for practical guidelines and assessment tools that can aid in evaluating their efficacy and safety. In this context, we propose a comprehensive checklist designed to guide researchers and clinicians in considering critical aspects when designing and conducting biomedical and clinical studies involving EVs. This checklist aims to enhance the standardization of trials and therapeutic procedures, ensuring that clinical reports are prepared with adequate detail. By controlling reproducibility and transparency in research, we believe that our proposed guidelines will contribute significantly to advancing the application of EVs in clinical practice.

Burn injuries are among the most devastating forms of trauma, leading to functional impairment, aesthetic disfigurement, and psychological distress. Traditional reconstructive methods using autografts often result in donor site morbidity and suboptimal cosmetic outcomes. Bioengineered skin substitutes offer an innovative approach to burn reconstruction, providing dermal and epidermal regeneration with reduced complications. This paper reviews recent developments, clinical outcomes, case studies, and the future of skin tissue engineering.

This paper explores a novel hybrid regenerative therapy combining umbilical cord-derived stem cells, regenerative capabilities observed in the spiny mouse (Acomys), and the immune pathways of Behçet’s disease. The paper proposes using Behçet’s vascular signaling behavior as a method of targeted delivery. While theoretical, the approach draws on real biological promise and suggests future experimental directions, including safe delivery mechanisms and integration with biosensing technologies. This work aims to shift chronic illness treatment from symptom management toward systemic regeneration.

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.

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. 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. 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. 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.

Revue d'information -3 numéros par an Tous les noms mentionnés dans ce numéro ont été modifiés afin de garantir l'anonymat. édito Il y a un moment, le dernier, où tout le monde est à égalité. Mais avant cela les inégalités, les injustices ne font que s'aggraver à mesure que le temps passe. Dans une société solidaire, une société digne de ce nom, les droits et les ressources devraient augmenter en même temps que l'âge avance et à mesure que les facultés diminuent. Nous savons que pour nombre de personnes âgées, ce n'est pas le cas. Pour les personnes âgées exilées tout est, comme toujours, plus compliqué, la solidarité existe mais elle est moins abordable. Souvent pauvres et fragiles, les personnes âgées exilées qui ont déjà vécu une vie d'épreuves et de combats vont devoir continuer à lutter à un moment où elles aspirent au repos. Cette façon de laisser prospérer, dans un pays riche, un système qui maltraite les vieux, les exilés et donc, mais de façon exponentielle, les vieux exilés, devrait nous couvrir de honte. Au lieu de cela, la maltraitance des exilés devient pour un nombre toujours plus grand de personnes une solution, une bonne idée, un projet politique et même une fierté. Les exilés sont en première ligne dans nos débats politiques, mais ils sont surtout en première ligne au travail : dans nos maisons, nos écoles, nos entreprises, nos hôpitaux, nos Ehpads ; ils stimulent notre économie, soutiennent nos familles, bien souvent, ils sont auprès des fragiles et des précaires, ils sont en première ligne pour répondre à nos besoins et combler nos insuffisances. Nous leur devons accueil, protection et intégration, au plus tôt et au mieux, dans la société. Ce numéro de Mémoires qui évoque la situation des personnes âgées exilées montre que nous en sommes loin. Le portrait-robot des personnes exilées âgées est difficile à dessiner tant les études ou statistiques sont rares 7 / Mémoires Dossier OCTOBRE 2024

2 REVISTA La Revista Redbioética/UNESCO es una revista de acceso abierto. Todo su contenido está libremente disponible sin cargo para usos lícitos por los usuarios y/o sus instituciones. Los lectores pueden leer, bajar, copiar, distribuir, imprimir y/o colocar hipervínculos al texto completo de los artículos sin requerir previamente autorización del autor o del editor, de acuerdo con la definición de acceso abierto de la BOAI (Budapest Open Access Initiative). La Revista Redbioética/UNESCO y los autores retienen, sin embargo, el derecho a ser adecuadamente citados. La Revista Redbioetica/UNESCO es una revista semestral on-line dedicada a la difusión y debate de la bioética en el ámbito de América Latina y el Caribe, que publica artículos originales revisados por pares externos, así como también presentaciones en congresos, crónicas, reseñas y noticias. Está dirigida tanto al público especializado en bioética como a la comunidad en general, y es de acceso abierto (según definición BO...

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.