Reconstruction of rat calvarial defects utilizing an ultraviolet-cured hydrogel loaded with bone marrow mesenchymal stem cells / 口腔疾病防治

Objective@#To investigate the osteogenic properties of a methacrylated gelatin (GelMA) / bone marrow mesenchymal stem cells (BMSCs) composite hydrogel applied to the skull defect area of rats and to provide an experimental basis for the development of bone regeneration biomaterials.@*Methods@#This study was approved by the Animal Ethics Committee of Nanjing University. A novel photocurable composite biohydrogel was developed by constructing photoinitiators [lthium phenyl (2,4,6-trimethylbenzoyl) phosphinate, LAP], GelMA, and BMSCs. The surface morphology and elemental composition of the gel were examined using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The compressive strength of the gel was evaluated using an electronic universal testing machine. After in vitro culture for 1, 2, and 5 days, the proliferation of the BMSCs in the hydrogels was assessed using a CCK-8 assay, and their survival and morphology were examined through confocal microscopy. A 5 mm critical bone deficiency model was generated in a rat skull. The group receiving composite hydrogel treatment was referred to as the GelMA/BMSCs group, whereas the untreated group served as the control group. At the 4th and 8th weeks, micro-CT scans were taken to measure the bone defect area and new bone index, while at the 8th week, skull samples from the defect area were subjected to H&E staining, van Gieson staining, and Goldner staining to evaluate the quality of bone regeneration and new bone formation.@*Results@#SEM observed that the solidified GelMA showed a 3D spongy gel network with uniform morphology, the porosity of GelMA was 73.41% and the pore size of GelMA was (28.75 ± 7.13) μm. EDX results showed that C and O were evenly distributed in the network macroporous structure of hydrogel. The hydrogel compression strength was 152 kPa. On the 5th day of GelMA/BMSCs culture, the cellular morphology transitioned from oval to spindle shaped under microscopic observation, accompanied by a significant increase in cell proliferation (159.4%, as determined by the CCK-8 assay). At 4 weeks after surgery, a 3D reconstructed micro-CT image revealed a minimal reduction in bone defect size within the control group and abundant new bone formation in the GelMA/BMSCs group. At 8 weeks after surgery, no significant changes were observed in the control group's bone defect area, with only limited evidence of new bone growth; however, substantial healing of skull defects was evident in the GelMA/BMSCs group. Quantitative analysis at both the 4- and 8-week examinations indicated significant improvements in the new bone volume (BV), new bone volume/total bone volume (BV/TV), bone surface (BS), and bone surface/total bone volume (BS/TV) in the GelMA/BMSCs group compared to those in the control group (P<0.05). Histological staining showed continuous and dense formation of bone tissue within the defects in the GelMA/BMSCs group and only sporadic formation of new bone, primarily consisting of fibrous connective tissue, at the defect edge in the control group.@*Conclusion@#Photocuring hydrogel-based stem cell therapy exhibits favorable biosafety profiles and has potential for clinical application by inducing new bone formation and promoting maturation within rat skull defects.

Advances in corneal stromal regeneration and repair / 国际眼科杂志(Guoji Yanke Zazhi)

Corneal stroma is a significant part of the cornea and plays a significant role in the eye's refractive system. Although corneal transplantation is now the most effective treatment for corneal stromal disease, its advancement has been constrained by a shortage of donors, the need for prolonged immunosuppressive medicine to prevent rejection, and low graft survival rates. An alternate strategy is to use the corneal stroma's natural capacity for regeneration to create the ideal conditions for the collagenous extracellular matrix of the stroma to self-renew. However, it is challenging to replicate the intricate ultrastructure of the corneal stroma in vitro. Regenerative medicine has so been used to address these issues. These approaches refer to numerous disciplines, including stem cell-induced differentiation, tissue engineering and gene editing. This article provides potential directions for the future clinical applications of corneal stromal regeneration and repair while summarizing pertinent techniques, research progress, and issues.

Research progress on association between macrophages and ischemia-reperfusion injury / 器官移植

Ischemia-reperfusion injury (IRI) is an extremely complicated pathophysiological process, which may occur during the process of myocardial infarction, stroke, organ transplantation and temporary interruption of blood flow during surgery, etc. As key molecules of immune system, macrophages play a vital role in the pathogenesis of IRI. M1 macrophages are pro-inflammatory cells and participate in the elimination of pathogens. M2 macrophages exert anti-inflammatory effect and participate in tissue repair and remodeling and extracellular matrix remodeling. The balance between macrophage phenotypes is of significance for the outcome and treatment of IRI. This article reviewed the role of macrophages in IRI, including the balance between M1/M2 macrophage phenotype, the mechanism of infiltration and recruitment into different ischemic tissues. In addition, the potential therapeutic strategies of targeting macrophages during IRI were also discussed, aiming to provide reference for alleviating IRI and promoting tissue repair.

Optimal diagnosis and treatment for renal allograft fibrosis / 器官移植

Renal allograft fibrosis is one of the common and severe complications after kidney transplantation, which seriously affects the function and survival rate of renal allograft, and may even lead to organ failure and patient death. At present, the researches on renal allograft fibrosis are highly complicated, including immunity, ischemia-reperfusion injury, infection and drug toxicity, etc. The diagnosis and treatment of renal allograft fibrosis remain extremely challenging. In this article, the latest research progress was reviewed and the causes, novel diagnosis and treatment strategies for renal allograft fibrosis were investigated. By improving diagnostic accuracy and optimizing treatment regimen, it is expected to enhance clinical prognosis of kidney transplant recipients, aiming to provide reference for clinicians to deliver proper management for kidney transplant recipients.

Injection of freshly collected adipose tissue for the treatment complex cryptoglandular anal fistula: case report

Introduction: Perianal fistula is a common colorectal disease which is caused mainly by cryptoglandular disease. Although most cases are treated successfully by surgery, management of complex perianal fistulas (CPAF) remains a challenge with limited results in recurrence and sometimes associated with fecal incontinence. The CPAF treatment with autologous adipose-derived mesenchymal stem cells (ASCs) had become a research hotspot. The technique started to be used in the treatment of Crohn's disease (CD) fistulas, where the studies showed safe and goods result from the procedure. Cultured ASCs have been used but this approach requires the preceding collection of adipose tissue, time for isolation of ASCs and subsequent in vitro expansion, need for laboratory facilities, and expertise in cell culturing. These factors have been getting over by using the commercially available alternative, allogenic ASCs. Treatment with allogeneic ASCs has shown good results in patients with CD fistulas, however with the disadvantage of being expensive. Objective: To show that the injection with freshly collected adipose tissue is an alternative to treatment with autologous or allogenic ASCs with several advantages. Methods: In this case report, we show our first experience in the treatment of CPAF with the application of collected adipose tissue in a tertiary referral hospital from Belo Horizonte, Brazil. Results The patient had a good postoperative recuperation with a complete fistula healing after 8 months without adverse effects. Conclusion: Injection with freshly collected adipose tissue is a promising and apparently safe sphincter-sparing technique in the treatment of CPAF. (AU)

CAR-T cell therapy for multiple myeloma: a practical toolkit for treatment in Brazil

ABSTRACT Introduction Chimeric antigen receptor T (CAR-T) cell therapy is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) that is a multi-step process involving various stakeholders. Appropriate education on the practical logistics is therefore paramount to ensure treatment success. Methods A group of key opinion leaders met to explore the key elements of setting up and running a CAR-T center in Brazil. For each step in the CAR-T cell therapy process, the experts agreed on basic requirements, gave their key recommendations from practical experience, and considered any remaining unanswered questions. Results This paper presents best-practice recommendations and advice on how to overcome common challenges for each step in the CAR-T cell therapy process, with a focus on the current situation in Brazil. Key themes throughout the process are collaboration within the multidisciplinary team and with the referring physician, along with communication and education for patients and their caregivers. Conclusion We believe that the expert insights presented in this paper, in particular on optimal patient selection and timing of CAR-T cell therapy, will deepen understanding of the CAR-T process and aid implementation of this novel therapy for patients with RRMM in Brazil.

Stem cell therapy in stargardt disease: a systematic review

This article aimed to review current literature on the safety and efficacy of stem cell therapy in Stargardt disease. A comprehensive literature search was performed, and two animal and eleven human clinical trials were retrieved. These studies utilized different kinds of stem cells, including human or mouse embryonic stem cells, mesenchymal stem cells, bone marrow mononuclear fraction, and autologous bone marrow-derived stem cells. In addition, different injection techniques including subretinal, intravitreal, and suprachoroidal space injections have been evaluated. Although stem cell therapy holds promise in improving visual function in patients with Stargardt disease, further investigation is needed to determine the long-term benefits, safety, and efficacy in determining the best delivery method and selecting the most appropriate stem cell type.

Current status and future of new technologies in the treatment of type 1 diabetes / 中国医师杂志

Type 1 diabetes mellitus (T1DM) is an organ-specific disease characterized by autoimmune damage to pancreatic β cells. Insulin therapy is the most basic and important treatment for T1DM, but insulin therapy cannot fundamentally terminate or improve the main cause of T1DM, namely the disorder of the immune regulation mechanism. With the advancement of science and technology, the continuous development of new insulin and hypoglycemic drugs has provided better means for glycemic control. Pancreas transplantation, islet transplantation, immunotherapy, and cell therapy have provided hope for the prevention or reversal of T1DM. It is of great significance to understand the current situation and future of new technologies for T1DM treatment for the research and management of T1DM patients.

Clinical research advance in immunotherapy of pancreatic cancer / 中华消化外科杂志

Pancreatic cancer is one of the most common tumors in digestive system, which is characterized by insidious clinical symptoms, strong invasion, easy metastasis and high mortality. In recent years, immunotherapy is a new direction to the treatment of solid tumors, but its applica-tion in pancreatic cancer is limited by tumor microenvironment of pancreatic cancer. The authors systematically analyze the tumor microenvironment of pancreatic cancer, summarize the clinical researches related to pancreatic cancer immunotherapy, and discuss the prospect of pancreatic cancer immunotherapy.

The value of ouantitative parameters of magnetic resonance imaging in predicting the efficacy of chimeric antigen receptor T-cell therapy for children and adolescents with mature aggressive B-cell non-Hodgkin lymphoma / 中华实用儿科临床杂志

Objective:To investigate the value of quantitative parameters of magnetic resonance imaging (MRI) in predicting the efficacy of chimeric antigen receptor T-cell (CAR-T) therapy for children and adolescents with mature aggressive B-cell non-Hodgkin lymphoma (NHL).Methods:It was a retrospective multicenter study.Clinical data of 44 children and adolescents diagnosed with mature aggressive B-cell NHL between January 2016 and January 2023 in Henan Cancer Hospital, Beijing Gaobo Boren Hospital, and the First Affiliated Hospital of Xinxiang Medical University were retrospectively analyzed.Patients were divided into complete response (CR) group and non-CR group based on the international criteria for the diagnosis of pediatric NHL.Quantitative parameters of MRI, including T2 signal intensity, the minimal apparent diffusion coefficient (ADCmin), maximal ADC (ADCmax), and the mean ADC (ADCmean) were measured before and within 2 weeks after CAR-T infusion.The correlation between the above parameters and the achievement of CR was analyzed.The intraclass correlation coefficient (ICC) was used to assess the inter-observer agreement among observers in measuring quantitative parameters of MRI.Differences between groups were analyzed using the independent sample t-test.Factors influencing CR were identified through the binary Logistic regression analysis, and a prediction model was established.Model performance was evaluated by plotting receiver operating characteristic (ROC) curves. Results:Significant differences were observed between the CR group and non-CR group in T2 signal intensity before CAR-T infusion (267±152 vs.364±160, P=0.048), and ADCmin (0.94±0.38 vs.0.53±0.28, P<0.05), ADCmax (1.73±0.69 vs.0.84±0.43, P<0.05), ADCmean (1.28±0.48 vs.0.67±0.33, P<0.05), and T2 signal intensity within 2 weeks after CAR-T infusion (198±139 vs.345±168, P=0.004). A univariate prediction model was created by introducing the above quantitative parameters.The area under the curve (AUC), specificity, sensitivity, and accuracy of T2 signal intensity before CAR-T infusion in predicting the efficacy on children and adolescents with mature aggressive B-cell NHL were 0.800, 84.0%, 57.9%, and 72.7%, respectively.The AUC, specificity, sensitivity, and accuracy of ADCmax within 2 weeks of CAR-T infusion were 0.958, 88.0%, 78.9%, and 84.1%, respectively.The AUC, specificity, sensitivity, and accuracy of T2 signal intensity within 2 weeks of CAR-T infusion were 0.869, 84.0%, 68.4%, and 77.3%, respectively. Conclusions:Quantitative parameters of MRI, including ADC values and T2 signal intensity, are of great significance in the early prediction of CAR-T therapy efficacy on children and adolescents with mature aggressive B-cell NHL.Among these parameters, ADCmax presents the strongest predictive performance and serves as a valuable indicator for predicting a complete response with CAR-T treatment.

Gut microbiome and tumor immunotherapy / 国际肿瘤学杂志

Neoplasms immunotherapy has made a major breakthrough in the clinical practice of refractory tumor. However, there are still individual differences in treatment results and drug resistance in clinical application. Gastrointestinal microbiome is gradually recognized as an immunoregulatory factor in recent years, and more and more studies have focused on its influences on the efficacy of tumor immunotherapy. Targeting gastrointestinal microbiota to improve the response of tumor patients to immunotherapy has potential clinical application value.

Research progress in quality research and evaluation of human mesenchymal stem cells / 国际生物医学工程杂志

As adult stem cells, human mesenchymal stem cells (hMSCs) have the potential for self-replication, renewal, and multidirection differentiation. Their unique biological function determines their wide clinical indications. Researchers can define the quality attributes of hMSCs according to clinical expectations. The quality study of hMSCs should consider microbiological safety, biological safety, cell biological properties, and biological effectiveness. Quality evaluation is a common physical, chemical, and biological evaluation method for hMSCs. Traditional product safety evaluation strategies cannot fully adapt to current technology and product usage characteristics. Researchers have developed new, effective evaluation methods based on current technology. In terms of product efficacy evaluation strategies, an efficacy evaluation system has been gradually established and standardized according to the intended clinical use and based on quality studies, which can enable researchers to evaluate hMSCs products more comprehensively at different stages and processes. In this paper, the progress of quality research and evaluation of human mesenchymal stem cells was reviewed to provide a reference for the utilization of stem cells in the field of regenerative medicine.

Advances in stem cells treatment of androgenetic alopecia / 中国药科大学学报

@#Androgenetic alopecia (AGA) is the most prominent type of progressive hair loss in humans.At present, medication is the main treatment for AGA, however, drug therapy has significant side-effects. Stem cells provide a new strategy for the treatment of AGA, because of their role in tissue repair and maintenance of microenvironmental homeostasis.This paper reviews the pathogenesis of AGA, discusses the defects of traditional drug therapy,and discusses the research progress of stem cells and stem cell derivatives in the treatment of AGA, in order to provide a comprehensive review of the prospects of stem cell therapy for AGA.

Liver graft preservation and functional maintenance accelerate the development of liver transplantation / 器官移植

As an effective treatment for end-stage liver disease, liver transplantation has been widely carried out worldwide and gradually captivated widespread recognition. With the advancement of liver transplantation techniques, the incidence of postoperative complications has been gradually declined, and the short-term and long-term prognosis of recipients have been constantly improved. However, a huge gap has existed between the supply and demand of donor organs, which is a major factors restricting the development of liver transplantation. The amount of liver transplantation operation in China is increasing year by year, the shortage of donor liver is becoming more and more prominent, and marginal donor liver is increasingly used in clinic. In recent years, the selection criteria of donor organs, organ preservation and functional maintenance have been continuously improved. In this article, the application and development trend of different techniques were reviewed from the perspectives of donor liver preservation and functional maintenance, and recent technical development and research results were summarized, aiming to provide reference for further enhancing the survival rate of grafts and recipients and promoting the development of liver transplantation in China.

Research progress of platelet lysates in the field of regenerative medicine and cell therapy / 中国输血杂志

Human platelet lysates(HPL), as a new type of biomaterial, can promote tissue repair, cell proliferation and inflammation control. This paper introduced the development of HPL in the field of regenerative medicine and cell therapy and summarizes their application. The potential of HPL to promote cell proliferation was used as an entry point to show its advantages as a supplement of cell culture medium. Since there is currently no standard procedure for HPL preparation, this paper sorts out the standardization elements such as raw materials source, donor variability and preparation technology, in order to provide reference for the establishment of standards of relevant industry in the future.

Effect and mechanism of extracorporeal photopheresis on preventing acute graft versus host disease in ice / 中国输血杂志

【Objective】 To investigate the preventive effects of early apoptotic splenic mononuclear cells induced by extracorporeal photopheresis (ECP) on acute graft versus host disease (aGVHD) in mice and explore the underlying mechanisms. 【Methods】 1) Splenic mononuclear cells were extracted from C57BL/6 mice and treated with different concentrations of 8-MOP (50 ng/mL, 100 ng/mL, 200 ng/mL, 300 ng/mL, 600 ng/mL). After treatment, irradiate the cells with 2 J/cm2 of ultraviolet light. Then, use the Annexin V-FITC/PI apoptosis detection kit to assess the early apoptosis rate of the cells and determine the optimal concentration of 8-MOP for the experiment.2) There were 35 SPF-grade female BALB/C mice (H-2Kd) aged 6-8 weeks. After whole-body irradiation with 8Gy X-rays, the mice were divided into five groups: sham irradiation group received intravenous infusion of 0.2 mL of normal saline, the syngeneic bone marrow transplantation group received intravenous infusion of 0.2 mL of BALB/C mouse bone marrow nucleated cell suspension (including a cell count of 1×107), the allogeneic bone marrow transplantation group received intravenous infusion of 0.2 mL of C57BL/6 mouse bone marrow nucleated cell suspension (including a cell count of 1×107), the aGVHD group received intravenous injection of a mixture of C57BL/6 mouse bone marrow nucleated cells (including a cell count of 1×107) and splenic mononuclear cells (including a cell count of 1×107) in 0.2 mL, the ECP prevention group received pre-transplant intravenous infusion of 0.2 mL of ECP-treated splenic mononuclear cells of C57BL/6 mice (including a cell count of 1×107 ) 48 hours before transplantation, and on the day of transplantation, intravenous injection of a mixture of C57BL/6 mouse bone marrow nucleated cells (including a cell count of 1×107) and splenic mononuclear cells (including a cell count of 1×107 ) in 0.2 mL.The preventive effects of ECP on aGVHD were observed, and the concentrations of IFN-γ, IL-2, TNF, IL-4 and IL-6 in mouse serum were measured using CBA. Th1 cell counts were determined by flow cytometry. 【Results】 Different concentrations of 8-MOP (50 ng/mL,100 ng/mL, 200 ng/mL, 300 ng/mL, 600 ng/mL) were used to treat mouse splenic mononuclear cells. The early apoptosis rates (%), observed after treatment were as follows: (14.18±0.865) vs (16.76±0.407) vs (18.83±0.404) vs (19.27±0.404) vs (14.5±0.529). The appropriate concentration of 8-MOP was determined to be 200 ng/mL.In vivo experiment, the results showed that the aGVHD group had decreased survival rate, reduced body weight, and increased clinical scores compared to the syngeneic and allogeneic bone marrow transplantation groups (P<0.01), and the chimerism of bone marrow cells in mice after transplantation was over 90%. ECP significantly improved the survival rate of mice after transplantation, reduced clinical scores (P<0.05), and decreased the concentrations of Th1 cell cytokines in serum (P<0.05) and the counts of Th1 cells in the spleen (P<0.05). 【Conclusion】 ECP-induced early apoptotic single nuclear cells from the spleen can prevent the occurrence of aGVHD by reducing the Th1 response in mouse.

Research and application progress in adoptive re-transfusion of regulatory cells in organ transplantation / 器官移植

Rejection and adverse reactions caused by long-term use of immunosuppressants severely affect the survival rate and quality of life of organ transplant recipients. Immune tolerance induction plays a key role in improving the survival rate and quality of life of organ transplant recipients. In recent years, tremendous progress has been achieved in adoptive re-transfusion of regulatory cells. In this article, research progress in regulatory T cell (Treg), myeloid-derived suppressor cell (MDSC) and regulatory B cell (Breg) in animal experiment and clinical application was reviewed, and the main clinical problems of adoptive re-transfusion of regulatory cells, the application of chimeric antigen receptor Treg and the concept of cell therapy in immune evaluation were summarized, aiming to deepen the understanding of regulatory cell therapy, promote the application of regulatory cells in immune tolerance of organ transplantation, and improve clinical efficacy of organ transplantation and the quality of life of recipients.

Reflections on the conduct of cell therapy clinical trials in medical institutes / 中华医学科研管理杂志

Objective:This paper introduces the concepts of " patient-centered cell therapy research management model", to provide reference for domestic medical institutions which conduct cell therapy clinical trials.Methods:We reviewed and summarized the experiences of conducting cell therapy at Peking University Shenzhen Hospital, including challenges and response plans regarding to the technology assessment, ethical evaluation risks and regulatory compliance. According to which, this paper aims to explore the reflections and practical experience of establishing a patient-centered, multi-stakeholder shared decision-making research management system.Results:The " patient-centered cell therapy research management model" ensures the reliability of research results through multi-stakeholder engagement in decision-making and management, adequate technical evaluation, effective ethical review and harmonized scientific research management, which not only meets the urgent health needs of the patient, but also promotes the standardized development of emerging technologies.Conclusions:The " patient-centered cell therapy research management model" is tailored for the cell therapy research, it is important to promote its further assessment and applications.

Mechanism of Kidney-tonifying and Anti-aging Chinese Medicines Combined with Stem Cell Therapy in Treatment of Alzheimer's Disease： A Review / 中国实验方剂学杂志

Alzheimer's disease （AD） is a neurodegenerative disease associated with aging and age-related cognitive decline. It is characterized by insidious onset and progressive development， and has become a major global health and socioeconomic issue. The exact mechanisms underlying AD have not been fully elucidated， and various hypotheses have been proposed by researchers based on different etiologies， including the amyloid β （Aβ） cascade hypothesis， Tau protein hyperphosphorylation hypothesis， mitochondrial dysfunction and oxidative stress hypothesis， and neurotransmitter hypothesis. Therefore， there is an urgent need for comprehensive interventions targeting multiple pathways， links， and targets. Based on traditional Chinese medicine （TCM） theory and modern research findings， kidney-tonifying and anti-aging Chinese medicines have unique advantages of toxicity reduction， long-lasting effects， and treating both the root cause and the symptoms. They have been shown to counteract immune-inflammatory responses， clear reactive oxygen species， exhibit antioxidant properties， inhibit abnormal aggregation of Aβ and Tau proteins， reduce neuronal apoptosis， regulate central neurotransmitters， and modulate gut microbiota in AD. In recent years， stem cell therapy has been explored for the treatment of AD through two strategies： endogenous activation and exogenous transplantation， thereby replenishing and replacing damaged neurons. However， factors such as blood-brain barrier permeability， targeted delivery to the affected area， immune rejection， and cell survival rate can affect the efficacy of stem cell transplantation. Therefore， combining stem cell therapy with medication and other methods can further enhance the effectiveness of stem cell transplantation. Kidney-tonifying and anti-aging Chinese medicines can activate dormant neural stem cells（NSCs） in the body， promote neuroregeneration， and facilitate tissue and organ repair and reconstruction in AD. The combined treatment of these Chinese medicines and stem cell transplantation has shown more significant efficacy compared to either treatment alone. This combination therapy provides a new integration point for the modernization of TCM and offers new ideas and approaches for the prevention and treatment of AD， as well as improving the effectiveness of stem cell transplantation.

Application and prospect of cell therapy in clinical treatment of liver diseases / 临床肝胆病杂志

Cell therapy is an emerging therapy different from traditional drug therapy, among which immune cells and mesenchymal stem cells are the two types of most promising cells in the treatment of liver diseases at present, and preliminary results have been achieved for their therapeutic effects. This article summarizes the advances in cell therapy in the field of liver diseases, analyzes the challenges and coping strategies of different cell therapies, and discusses the application prospects of cell therapy in liver-related diseases.