Cell Therapy Research Articles

Stem Cells Treatment for Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) refers to bleeding in the subarachnoid space, which is a serious neurologic emergency. However, the treatment effects of SAH are limited. In recent years, stem cell (SC) therapy has gradually become a very promising therapeutic method and advanced scientific research area for SAH. The SCs used for SAH treatment are mainly bone marrow mesenchymal stem cells (BMSCs), umbilical cord mesenchymal stem cells (hUC-MSCs), dental pulp stem cells (DPSCs), neural stem cells (NSCs)/neural progenitor cell (NPC), and endothelial progenitor cell (EPC). The mechanisms mainly included differentiation and migration of SCs for tissue repair; alleviating neuronal apoptosis; anti-inflammatory effects; and blood-brain barrier (BBB) protection. The dosage of SCs was generally 106 orders of magnitude. The administration methods included intravenous injection, nasal, occipital foramen magnum, and intraventricular administration. The administration time is generally 1 hour after SAH modeling, but it may be as late as 24 hours or 6 days. Existing studies have confirmed the neuroprotective effect of SCs in the treatment of SAH. SC has great potential application value in SAH treatment, a few case reports have provided support for this. However, the relevant research is still insufficient and there is still a lack of clinical research on the SC treatment for SAH to further evaluate the effectiveness and safety before it can go from experiment to clinical application.

Exploring cutting-edge approaches in diabetes care: from nanotechnology to personalized therapeutics.

Diabetes mellitus (DM) is a persistent condition characterized by high levels of glucose in the blood due to irregularities in the secretion of insulin, its action, or both. The disease was believed to be incurable until insulin was extracted, refined, and produced for sale. In DM, insulin delivery devices and insulin analogs have improved glycemic management even further. Sulfonylureas, biguanides, alpha-glucosidase inhibitors, and thiazolidinediones are examples of newer-generation medications having high efficacy in decreasing hyperglycemia as a result of scientific and technological advancements. Incretin mimetics, dual glucose-dependent insulinotropic polypeptide, GLP-1 agonists, PPARs, dipeptidyl peptidase-4 inhibitors, anti-CD3 mAbs, glucokinase activators, and glimins as targets have all performed well in recent clinical studies. Considerable focus was placed on free FA receptor 1 agonist, protein tyrosine phosphatase-1B inhibitors, and Sparc-related modular calcium-binding protein 1 which are still being studied. Theranostics, stem cell therapy, gene therapy, siRNA, and nanotechnology are some of the new therapeutic techniques. Traditional Chinese medicinal plants will also be discussed. This study seeks to present a comprehensive analysis of the latest research advancements, the emerging trends in medication therapy, and the utilization of delivery systems in treating DM. The objective is to provide valuable insights into the application of different pharmaceuticals in the field of diabetes mellitus treatment. Also, the therapeutic approach for diabetic patients infected with COVID-19 will be highlighted. Recent clinical and experimental studies evidence the Egyptian experience. Finally, as per the knowledge of the state of the art, our conclusion and future perspective will be declared.

Therapeutic advances in hepatocellular carcinoma: an update from the 2024 ASCO annual meeting

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide. Recent advances in immunotherapies, targeted therapies, and combination treatments have significantly improved outcomes for many patients with HCC. This review summarizes key findings from the 2024 ASCO Annual Meeting, focusing on emerging therapies, including immune checkpoint inhibitors (ICIs), CAR-T cell therapies, oncolytic viruses, and locoregional treatments like transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC). ICIs, particularly when combined with other agents, have shown promising efficacy, though challenges such as immune-related adverse events and resistance mechanisms remain. CAR-T cell therapies and oncolytic viruses offer novel therapeutic avenues for advanced HCC, but their long-term efficacy in solid tumors is still under investigation. Locoregional therapies, especially in combination with systemic treatments, continue to play a critical role in managing unresectable HCC and improving conversion rates to surgical resection. Additionally, the potential of biomarkers, such as hypoxia scores and CTNNB1 mutations, is being explored to better personalize treatment and predict patient responses. These biomarkers could pave the way for more targeted and effective therapeutic strategies. Overall, the recent studies presented at the ASCO meeting highlight progress in HCC treatment, underscoring the importance of continued innovation. Future research should focus on overcoming resistance mechanisms, optimizing combination therapies, and integrating biomarker-driven approaches to improve patient outcomes and enhance personalized treatment strategies.

Safety of a Medicinal Product Based on Human Glial Progenitor Cells: A Pilot Study of Retrobulbar Administration in C57BL/6J Mice

INTRODUCTION. Stem cell therapy is a promising treatment method for various diseases and injuries, but its safety has yet to be determined. Therefore, studying the safety of administering a xenogeneic cell-based medicinal product (CBMP) into the retro-orbital venous sinus is essential for developing protocols for further studies of potential medicinal products for neurological conditions.AIM. The aim of the study was to determine the optimal dose of a CBMP derived from glial progenitor cells (GPCs) and to evaluate its safety during retrobulbar administration in C57BL/6J mice.MATERIALS AND METHODS. GPCs were derived from human induced pluripotent stem cells by stepwise differentiation and cultured in DMEM/F12 supplemented with epidermal growth factor and ciliary neurotrophic factor. Matrigel was used as a substrate. GPCs were injected into the retro-orbital venous sinus of male C57BL/6J mice under isoflurane anaesthesia once a week for two months. The study analysed changes in biochemical blood parameters and behaviour. The quantities of activated astrocytes and glial cells were determined by postmortem immunohistochemical staining.RESULTS. The administration of GPCs at a dose of 500×103 cells/mouse, which was selected using literature data, induced an increase in the plasma levels of ala nine aminotransferase and aspartate aminotransferase. This could indicate cell damage and the development of inflammatory reactions. At doses reduced to one-third the initial GPC concentration or lower, the biochemical blood parameters of the treatment groups did not differ significantly from those of the control group. There were no significant differences in neuroinflammatory markers between the groups receiving GPCs at different doses, except for an increase in astrocyte activation at a dose of 150×103 cells/mouse, which could potentially indicate inflammatory processes in the brain. The study detected no pathological changes in the brain or cell damage markers in the blood of mice after retrobulbar GPC injections of 15×103 or 50×103 cells/mouse.CONCLUSIONS. The study results indicate that long-term therapy with GPCs is potentially safe for mice if the dose is optimal. The authors suggest using the optimal doses and the administration route established in this study for further research into the safety of intravenous administration of CBMPs for neurological conditions.

Cryobiological Aspects of Upscaling Cryopreservation for Encapsulated Liver Cell Therapies

For the efficient delivery of a cell therapy a treatment must be provided rapidly, at clinical scale, contain a sufficient active cellular component (biomass), and adhere to a multitude of regulatory requirements. Cryopreservation permits many of these demands to be met more readily. Here we present the cryopreservation and recovery of large volume (2.5L) alginate encapsulated liver cell spheroids (AELS), suitable for use with a novel bioartificial liver device (HepatiCan™) for the treatment of those suffering from acute liver failure (ALF), in regulatory approved cryobags and a cryopreservation process optimised for large volumes. By first assessing the thermal profiles of large scale cryobags with a thermal mimic, the feasibility of cryopreserving a full patient dose simultaneously (3x cryobags containing 833ml biomass each) was investigated, allowing for small and subsequently large-scale testing of cellular functional recoveries. Work presented here demonstrates that optimised reproducible cooling and warming profiles could be achieved with these large volumes, leading to high biomass recoveries at full clinical scale. The recovered AELS also had high regeneration potential, achieving full pre-freeze viable cell densities within 3 days, indicating that the cell therapy could be delivered rapidly to patients with ALF. This study has presented the feasibility for rapid delivery of large volume cell therapies, whilst further research into improved speed of post-thaw recovery is warranted.

Releasing our model T - chimeric antigen receptor (CAR) T-cells for autoimmune indications.

This review provides an update on the rapidly growing field of engineered cellular therapies for autoimmune disorders, primarily focusing on clinical experience and correlative studies with chimeric antigen receptor (CAR) T-cells. To date, two case series describing treatment with CAR T-cell therapy for systemic lupus erythematosus (SLE) suggest that drug-free remission can be sustained in patients with previously treatment-refractory disease. The outcomes of these studies are similar, despite the use of different CAR constructs and lymphodepletion regimens. Although it is not yet clear whether the patients described have truly been cured, the majority of remissions have remained durable up to last follow-up at 1-2 years from treatment. Meanwhile, mechanistic studies are providing a window into how transient B-cell depletion mediates lasting benefit. With the encouraging data in SLE, CAR T-cells and other novel B-cell-depleting agents (e.g. bispecific T-cell engagers) are now being evaluated as treatment for other autoimmune conditions, with the goal of durable response. Recent reports highlight cellular therapies as a promising strategy for patients with treatment-refractory autoimmune conditions; however, there is still limited experience, and better insight into this therapeutic approach is expected to emerge rapidly.

Incidentally cured psoriasis in a patient with refractory/relapsed diffuse large B-cell lymphoma receiving CD19 CAR-T cell therapy: a case report

Chimeric antigen receptor T (CAR-T) cell therapy is a new treatment for cancers, but reports on curing immune-related skin diseases are limited. We report a case of successful CAR-T-cell therapy in a patient with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) who was incidentally cured of chronic generalized plaque psoriasis. The patient, a 65-year-old male who had a known history of psoriasis for 45 years, did not receive immunotherapy for psoriasis during this period. Imaging, molecular biology and immunology diagnostics confirmed DLBCL. After several weeks of standard-dose R-CHOP chemotherapy, the patient achieved partial remission, but according to CT, the patient relapsed, and there was no significant improvement in her psoriasis symptoms. Subsequently, the patient was enrolled in the CD19 CAR-T-cell therapy group. Four weeks after CAR-T-cell infusion, the patient’s abdominal pain disappeared, and there was a significant improvement in overall skin lesions. One year later, follow-up results indicated complete remission of R/R DLBCL (confirmed by PET-CT), with only minimal residual psoriatic skin lesions limited to the patient’s neck. The results of using CAR-T-cell therapy to achieve an incidental cure for psoriasis highlight the potential for exploring cell-based therapies for complex autoinflammatory skin diseases.

A refined TTC assay precisely detects cardiac injury and cellular viability in the infarcted mouse heart

Histological analysis with 2,3,5-triphenyltetrazolium chloride (TTC) staining is the most frequently used tool to detect myocardial ischemia/reperfusion injury. However, its practicality is often challenged by poor image quality in gross histology, leading to an equivocal infarct-boundary delineation and potentially compromised measurement accuracy. Here, we introduce several crucial refinements in staining protocol and sample processing, which enable TTC images to be analyzed with light microscopy. The refined protocol involves a two-step TTC staining process (perfusion and immersion) and subsequent Zamboni fixation to differentiate myocardial viability and necrosis, and use of Coomassie brilliant blue to label area-at-risk. After the duo-staining steps were completed, the heart sample was embedded and sliced transversally by a cryostat into a series of thin sections (50 µm) for microscopic analysis. The refined TTC (redTTC) assay yielded remarkably high-quality images with striking color intensity and sharply defined boundaries, permitting unambiguous and reliable delineation of the infarct and area-at-risk. In the same animals, the redTTC assay showed good agreement with the in-vivo gold standard measurements (LGE and MEMRI). Meanwhile, redTTC imaging allows tracking of viable cardiomyocytes at cellular resolution, and with this enhanced capability, we convincingly demonstrated the pro-survival action of stem cells based-therapy. Therefore, the redTTC assay represents a significant technical advance that permits precise detection of the true extent of cardiac injury and cardiomyocyte viability. This approach is cost-effective and may be adapted for use in diverse applications, making it highly appealing to many laboratories performing ischemia/reperfusion injury experiments.

Mesenchymal Stem Cells Engineered by Multicomponent Coassembled DNA Nanofibers for Enhanced Wound Healing.

A major challenge for stem cell therapies, such as using mesenchymal stem cells to treat skin injuries, is the stable engraftment of exogenous cells and the maintenance of their regenerative capacities in the wound areas. DNA-based self-assembly strategies can be used for artificial and multifunctional cell surface engineering to stabilize and enhance their functions for therapeutic applications. Here, we developed DNA nanofiber-decorated stem cells, in which DNA-based, multivalent fiber-like structures were self-assembled in situ on the cell surfaces. These engineered stem cells have demonstrated robust reactive oxygen species (ROS) scavenging effects, specific adhesion to damaged vascular endothelial cells, and the ability to enhance angiogenesis, which were effective and safe for acute or chronic wound healing in a mouse model with excisional skin injury. This DNA nanostructure-engineered stem cell provides a novel therapeutic platform for the treatment of tissue damage.

Synthesizing regulatory guidance for demonstrating preclinical efficacy and translating promising cell therapies to early phase clinical trials: a scoping review

BackgroundRegulatory applications for cell therapy face more objections compared to conventional small molecule or biological drugs, leading to delays in market approval and clinical adoption. Increased regulatory objections frequently relate to issues regarding preclinical evidence, such as experimental design of animal studies, selection of animal models, endpoints, and determination of mechanism of action. Synthesis and clarification of the preclinical evidence necessary to demonstrate treatment efficacy and advance into early-phase clinical trials is needed to help researchers avoid regulatory objections.MethodsWe conducted a scoping review in which we searched repositories of the International Council for Harmonisation and all national member organizations (N = 38) for documents related to preclinical studies of cell therapies. Active guidance documents related to cell therapy were included, with no restrictions based on the year or language of publication. Data extraction was conducted in duplicate with conflicts resolved through consensus discussion.ResultsFrom 1215 identified documents, a total of 182 were included and analyzed, with 71% originating from ten major regulatory agencies. The most prevalent preclinical item addressed was the mechanism of action (n = 161, 88% of documents), underscoring its importance in bridging preclinical findings to clinical application. Most documents (n = 140, 77%) emphasized the importance of using clinically relevant preclinical models, though specific recommendations on models of disease were less common (n = 81, 45%). Selection of clinically relevant intervention parameters (n = 136, 75%) and outcome measures (n = 121, 66%) were also frequently recommended, but selection of relevant comparator groups appeared less frequently (n = 35, 19%). Furthermore, robust study design elements such as randomization and blinding were less frequently recommended, appearing in 31% of documents (n = 57). Comparison with clinical trial guidance revealed a significant gap in the rigor of study design recommendations for preclinical research.ConclusionsRegulatory guidance for preclinical efficacy studies often recommends a strong emphasis on the clinical relevance of animal models, intervention parameters, outcomes, and mechanism of action. Incorporating these recommendations into early preclinical studies should improve the acceptability of preclinical evidence for approval by the relevant national regulators and can be used as a guide to ensure that all evidence that regulators say they expect is efficiently assembled into new clinical trial applications.

Enhancing differentiation and functionality of insulin-producing cells derived from iPSCs using esterified collagen hydrogel for cell therapy in diabetes mellitus

BackgroundIslet transplantation is a recommended treatment for type 1 diabetes but is limited by donor organ shortage. This study introduces an innovative approach for improving the differentiation and functionality of insulin-producing cells (IPCs) from iPSCs using 3D spheroid formation and hydrogel matrix as an alternative pancreatic islet source. The extracellular matrix (ECM) is crucial for pancreatic islet functionality, but finding the ideal matrix for β-cell differentiation has been challenging. We aimed to advance IPC differentiation and maturation through an esterified collagen hydrogel, comparing its effectiveness with conventional basement membrane extract (BME) hydrogels.MethodsiPSCs were differentiated into IPCs using a small molecule-based sequential protocol, followed by spheroid formation in concave microwells. Rheological analysis, scanning electron microscopy, and proteomic profiling were used to characterize the chemical and physical properties of each matrix. IPCs, both in single-cell form and as spheroids, were embedded in either ionized collagen or BME hydrogels, which was followed by assessments of morphological changes, pancreatic islet-related gene expression, insulin secretion, and pathway activation using comprehensive analytical techniques.ResultsEsterified collagen hydrogels markedly improved the structural integrity, insulin expression, and cell-cell interactions in IPC spheroids, forming densely packed insulin-expressing clusters, in contrast to the dispersed cells observed in BME cultures. Collagen hydrogel significantly enhanced the mRNA expression of crucial endocrine markers and maturation factors, with IPC spheroids showing accelerated differentiation from day 5, suggesting a faster differentiation compared to single cells in hydrogel encapsulation. Insulin secretion in response to glucose in collagen environments, with a GSIS index of 2.46 ± 0.05, exceeded those in 2D and BME, demonstrating superior pancreatic islet functionality. Pathway analysis highlighted enhanced insulin secretion capabilities, evidenced by the upregulation of genes like Secretogranin III and Chromogranin A in collagen cultures. In vivo transplantation results showed that collagen hydrogel enhanced cluster integrity, tissue integration, and insulin secretion compared to non-embedded IPCs and BME groups.ConclusionEsterified collagen hydrogels demonstrated superior efficacy over 2D and BME in promoting IPC differentiation and maturation, possibly through upregulation of the expression of key secretion pathway genes. Our findings suggest that using collagen hydrogels presents a promising approach to enhance insulin secretion efficiency in differentiating pancreatic β-cells, advancing cell therapy in diabetes cell therapy.

Digital Magnetic Sorting for Fractionating Cell Populations with Variable Antigen Expression in Cell Therapy Process Development

Cellular therapies exhibit immense potential in treating complex diseases with sustained responses. The manufacture of cell therapies involves the purification and engineering of specific cells from a donor or patient to achieve a therapeutic response upon injection. Magnetic cell sorting targeting the presence or absence of surface markers is commonly used for upfront purification. However, emerging research shows that optimal therapeutic phenotypes are characterized not only by the presence or absence of specific antigens but also by antigen density. Unfortunately, current cell purification tools like magnetic or fluorescence-activated cell sorting (FACS) lack the resolution to differentiate populations based on antigen density while maintaining scalability. Utilizing a technique known as digital magnetic sorting (DMS), we demonstrate proof of concept for a scalable, magnetic-based approach to fractionate cell populations based on antigen density level. Targeting CD4 on human leukocytes, DMS demonstrated fractionation into CD4Hi T cells and CD4Low monocytes and neutrophils as quantified by flow cytometry and single-cell RNA seq. DMS also demonstrated high throughput processing at throughputs 3–10× faster than FACS. We believe DMS can be leveraged and scaled to enable antigen density-based sorting in cell therapy manufacturing, leading to the production of more potent and sustainable cellular therapies.

Expanding Human Breg for Cellular Therapy in Transplantation: Time for Translation.

Regulatory B cells (Breg) are instrumental in protecting allografts in transplantation. Breg signatures are identified in operationally tolerant human kidney transplant recipients and can predict organ survival and acute rejection. Animal models of transplantation and autoimmunity support the use of Breg as an adoptive cellular therapy. Detailed mechanistic studies have identified multiple signaling pathways utilized by Breg in their induction, expansion, and downstream function. These preclinical studies provide the guiding principles, which will inform protocols by which to expand this crucial immunoregulatory population before clinical use. There is an urgent need for novel therapies to improve long-term transplant outcomes and to minimize immunosuppression-related morbidity including life-threatening infection and cancer. Systematic evaluation of the signals, which drive Breg expansion, will be key to transforming the as of yet unharnessed potential of this potent immunoregulatory cell. In this review, we explore the potential avenues of translating Breg subsets from cell culture at the laboratory bench to cell therapy at the patient's bedside. We will discuss the standardization of Breg phenotypes to aid in precursor population selection and quality control of a Breg-cell therapy product. We will evaluate avenues by which to optimize protocols to drive human Breg expansion to levels sufficient for cellular therapy. Finally, we will examine the steps required in process development including scalable culture systems and quality control measures to deliver a viable Breg-cell therapy product for administration to a transplant recipient.

Navigating the therapeutic landscape for breast cancer: targeting breast cancer stem cells.

Breast cancer is a common and deadly malignancy that affects women globally, and breast cancer stem cells (BCSCs) play an important role in tumorigenesis, development, metastasis, and recurrence. Traditional therapies often fail to eliminate BCSCs, leading to treatment resistance and relapse. This review explores the therapeutic strategies which are designed to target BCSCs, including inhibition of key signaling pathway and targeting receptor. This paper also explores the approaches to targeting BCSCs including chemotherapy, phytomedicines, and nanotechnology. Nanotechnology has gained a lot of importance in cancer therapy because of its ability to deliver therapeutic agents with more precision and minimal side effects. Various chemotherapeutic drugs, siRNAs, or gene editing tools are delivered efficiently with the use of nanocarriers which target pathways, receptors, and proteins associated with BCSCs. Over the past few years, stimuli-responsive and receptor-targeted nanocarriers have been explored for better therapeutic effects. In recent times, strategies such as chimeric antigen receptor (CAR) T-cell therapy, ablation therapy, and cell-free therapies are explored for targeting these stem cells. This review provides a recent developmental overview of strategies to attack BCSCs from conventional chemotherapeutic agents to nanotechnological platforms such as polymeric, lipidic, and metal-based nanoparticles and advanced technologies like CAR T cell therapies.

Antibiotic-induced loss of gut microbiome metabolic output correlates with clinical responses to CAR-T cell therapy

Antibiotic-induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cell therapies. In this study, we observed that prior exposure to broad-spectrum ABX with extended anaerobic coverage like piperacillin-tazobactam and meropenem was associated with worsened anti-CD19 CAR-T therapy survival outcomes in large B-cell lymphoma patients (n=422), compared to other ABX classes. In a discovery subset of these patients (n=67), we found that the use of these ABX was in turn associated with substantial dysbiosis of gut microbiome function, resulting in significant alterations of the gut and blood metabolome, including microbial effectors such as short-chain fatty acids (SCFAs) and other anionic metabolites, findings that were largely reproduced in an external validation cohort (n=58). Broader evaluation of circulating microbial metabolites revealed reductions in indole and cresol derivatives, as well as trimethylamine N-oxide, in patients who received ABX treatment (discovery n=40, validation n=28). These findings were recapitulated in an immune-competent CAR-T mouse model, where meropenem-induced dysbiosis led to a systemic dysmetabolome and decreased murine anti-CD19 CAR-T efficacy. Furthermore, we demonstrate that SCFAs can enhance the metabolic fitness of CAR-T cells, leading to improved tumor killing capacity. Together, these results suggest that broad-spectrum ABX deplete metabolically active commensals whose metabolites are essential for enhancing CAR-T efficacy, shedding light on the intricate relationship between ABX exposure, microbiome function and their impact on CAR-T cell efficacy. This highlights the potential for modulating the microbiome to augment CAR-T immunotherapy.

Optogenetically engineered Septin-7 enhances immune cell infiltration of tumor spheroids

Chimeric antigen receptor T cell therapies have achieved great success in eradicating some liquid tumors, whereas the preclinical results in treating solid tumors have proven less decisive. One of the principal challenges in solid tumor treatment is the physical barrier composed of a dense extracellular matrix, which prevents immune cells from penetrating the tissue to attack intratumoral cancer cells. Here, we improve immune cell infiltration into solid tumors by manipulating septin-7 functions in cells. Using protein allosteric design, we reprogram the three-dimensional structure of septin-7 and insert a blue light-responsive light-oxygen-voltage-sensing domain 2 (LOV2), creating a light-controllable septin-7-LOV2 hybrid protein. Blue light inhibits septin-7 function in live cells, inducing extended cell protrusions and cell polarization, enhancing cell transmigration efficiency through confining spaces. We genetically edited human natural killer cell line (NK92) and mouse primary CD8+ T-cells expressing the engineered protein, and we demonstrated improved penetration and cytotoxicity against various tumor spheroid models. Our proposed strategy to enhance immune cell infiltration is compatible with other methodologies and therefore, could be used in combination to further improve cell-based immunotherapies against solid tumors.

Design and In Vitro Evaluation of Fluorescent MOF-Core CaCO₃-PEI-FA Shell Nanoparticles for Targeted Therapy of Laryngeal Cancer Cells.

Laryngeal cancer, a common malignant respiratory tumor, is primarily treated through surgery. However, challenges such as recurrence, metastasis, and drug resistance persist. In recent years, multifunctional drug delivery systems (DDS) based on nanoparticles have shown great potential in improving drug loading and release. We developed a biocompatible core-shell nanoparticle system with a zinc-based metal-organic framework (MOF) as the core, named CP1. The shell, composed of polyethyleneimine (PEI), folic acid, and calcium carbonate, forms a composite called CaCO3-PEI-FA. This system enhances biocompatibility and increases the efficacy of biomedical applications. Encapsulating CP1 within the CaCO3-PEI-FA shell allows for the targeted delivery of the anticancer drug doxorubicin (DOX) to laryngeal cancer cells (Hep-2), resulting in the CaCO3-PEI-FA@CP1@DOX system. The CaCO3-PEI-FA composite exhibits strong fluorescence with a peak around 350nm, confirming successful synthesis and demonstrating its potential as a bioimaging probe. Importantly, the nanoparticle system without DOX showed low toxicity to normal human skin fibroblasts (HSF). In vitro cytology experiments revealed a 38% inhibition rate of Hep-2 cells after 24h, highlighting the nanocomposite's significant potential in inhibiting laryngeal cancer cell proliferation and inducing apoptosis, underscoring its promise in targeted laryngeal cancer therapy.

Intracavernosal mesenchymal stem cell therapy in ischaemic priapism: an experimental study.

The most common form of priapism is ischaemic and its prevalence in men has increased in recent years as a result of intracavernosal drug use. Currently, there is no approved specific treatment for ischaemic priapism other than cavernosal aspiration, which can only provide detumescence. This study aims to evaluate the efficacy of intracavernosal mesenchymal stem cell (MSC) therapy in an ischaemic priapism model. Thirty male Wistar albino rats were divided into three groups: sham (n = 6), priapism (n = 12) and priapism + MSC treatment (n = 12). The experimental groups were also divided into 1 and 12h subgroups of ischaemic priapism. The experimental model was created using a vacuum erection device and constrictive tape technique, and intracavernosal MSC were applied immediately after the tape was removed. After 4weeks, intracavernosal pressures (ICPs) and systemic mean arterial pressure (MAP) were measured. Penectomy was then performed to assess histopathological and molecular changes in the rats' penile tissues. In the ischaemic priapism model, MSC therapy showed significant improvements in peak and mean ICPs and mean ICP/MAP ratio. Histopathological analysis showed significant increases in smooth-muscle/collagen ratio and e-NOS and n-NOS expression. Although there was a decrease in fibrosis, it was not significant. At the molecular level, there were significant decreases in TGF-beta and VEGF mRNA expression, whilst NGF and BDNF mRNA-expression levels showed significant increases with MSC therapy. In terms of ICPs, the therapy showed more significant improvements in short-term priapism. However, when looking at histopathological and molecular parameters, the therapy had positive effects on a wider range of parameters in the long-term priapism. MSC treatment improved cavernosal physiology and had positive effects at the histopathological and molecular level in the ischaemic priapism model.

Preserving Stem Cells for Potential Use in Future Reparative Medicine

With its enormous potential for regenerative medicine and therapeutic applications, stem cell preservation represents a major breakthrough in biomedical science. Stem cells are gathered, processed, and stored under carefully monitored circumstances in order to preserve their viability for potential use in the future. Because they may differentiate into a variety of cell types, stem cells—especially those derived from sources like umbilical cord blood—are essential for both therapeutic and research uses. An essential function of cord blood banking is to offer a plentiful supply of immune system cells that may be stored for potential future therapeutic applications. Immunological deficits, osteoarthritis, Parkinson's disease, and heart failure are just a few of the conditions for which stem cell treatments have shown promise. Notwithstanding the promise, there remain obstacles such immunological rejection and the need for more research to fully comprehend the development and functionality of stem cells. It is essential for the general public to be informed about stem cell treatments and cord blood banking in order for expectant parents to make well-informed decisions. Future advancements in the subject depend heavily on resolving ethical issues and enhancing the effectiveness of stem cell-based therapies. To fully realise the promise of stem cell preservation in conventional medicine, more research, creativity, and international cooperation are required.

Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling

Tendon repair remains challenging due to its poor intrinsic healing capacity, and stem cell therapy has emerged as a promising strategy to promote tendon regeneration. Nevertheless, the inflammatory environment following acute tendon injuries disrupts stem cell differentiation, leading to unsatisfied outcomes. Our study recognized the critical role of NF-κB signaling in activating inflammation and suppressing tenogenic differentiation of stem cells after acute tendon injury via multiomics analysis. TPCA-1, a selective inhibitor of IKKβ/NF-κB signaling, efficiently restored the impaired tenogenesis of stem cells in the inflammatory environment. By developing a microsphere-incorporated hydrogel system for stem cell delivery and controlled release of TPCA-1, we successfully engineered a pro-tenogenic niche to initiate tenogenesis for tendon regeneration. Collectively, we recognize NF-κB signaling as a critical target to tailor a pro-tenogenic niche and propose the combined delivery of stem cells and TPCA-1 as a potential strategy for acute tendon injuries.