Oxidative stress induces ferroptosis in tendon stem cells by regulating mitophagy through cGAS-STING pathway.

Tendinopathy is one of the most prevalent sports injury diseases in orthopedics. However, there is no effective treatment or medicine. Recently, the discovery of tendon stem cells (TSCs) provides a new perspective to find new therapeutic methods for Tendinopathy. Studies have shown that oxidative stress will inevitably cause TSCs injury during tendinopathy, but the mechanism has not been fully elucidated. Here, we report the oxidative damage of TSCs induced by H2O2 via ferroptosis, as well, treatment with H2O2 raised the proportion of mitochondria engulfed by autophagosomes in TSCs. The suppression of mitophagy by Mdivi-1 significantly attenuates the H2O2-induced ferroptosis in TSCs. Mechanically, H2O2 actives the cGAS-STING pathway, which can regulate the level of mitophagy. Interfering with cGAS could impair mitophagy and the classical ferroptotic events. In the rat model of tendinopathy, interference of cGAS could relieve tendon injury by inhibiting ferroptosis. Overall, these results provided novel implications to reveal the molecular mechanism of tendinopathy, by which pointed to cGAS as a potential therapeutic target for the treatment of tendinopathy.

Stem cell treatment reduces T cell apoptosis in COPD patients with chronic bronchitis but not with emphysema.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent and preventable condition. Mesenchymal stem cell (MSC) therapy is being explored to aid in the regeneration of lung cells and airway structure, aiming to restore lung function. AIM: To examine varied responses of MSCs when cultured with peripheral blood mononuclear cells (PBMCs) from different COPD phenotypes, patients were grouped into ACOS, emphysema, and chronic bronchitis categories. METHODS: PBMCs from these groups and controls were co-cultured with MSCs derived from dental follicles, revealing differing rates of apoptosis among COPD phenotypes compared to controls. RESULTS: While the chronic bronchitis group exhibited the least lymphocyte viability (p<0.01), introducing MSCs notably enhanced viability across all phenotypes except emphysema, with the chronic bronchitis group showing the most improvement (p<0.05). CONCLUSION: Stem cell therapy might reduce peripheral lymphocyte apoptosis in COPD, with varying responses based on phenotype, necessitating further research to understand mechanisms and optimize tailored therapies for each COPD subtype.

Spermatogonial stem cell technologies: applications from human medicine to wildlife conservation.

Spermatogonial stem cell (SSC) technologies that are currently under clinical development to reverse human infertility hold the potential to be adapted and applied for the conservation of endangered and vulnerable wildlife species. The biobanking of testis tissue containing SSCs from wildlife species, aligned with that occurring in pediatric human patients, could facilitate strategies to improve the genetic diversity and fitness of endangered populations. Approaches to utilize these SSCs could include spermatogonial transplantation or testis tissue grafting into a donor animal of the same or a closely related species, or in vitro spermatogenesis paired with assisted reproduction approaches. The primary roadblock to progress in this field is a lack of fundamental knowledge of SSC biology in non-model species. Herein, we review the current understanding of molecular mechanisms controlling SSC function in laboratory rodents and humans, and given our particular interest in the conservation of Australian marsupials, use a subset of these species as a case-study to demonstrate gaps-in-knowledge that are common to wildlife. Additionally, we review progress in the development and application of SSC technologies in fertility clinics and consider the translation potential of these techniques for species conservation pipelines.

Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus. / 人脐带间å 质干细胞通过IGF1R-CHK2-p53信号轴减轻2åž‹ç³–å°¿ç— é›„æ€§å¤§é¼ ç³–å°¿ç— è‚¾ç— .

Diabetes mellitus (DM) is a disease syndrome characterized by chronic hyperglycaemia. A long-term high-glucose environment leads to reactive oxygen species (ROS) production and nuclear DNA damage. Human umbilical cord mesenchymal stem cell (HUcMSC) infusion induces significant antidiabetic effects in type 2 diabetes mellitus (T2DM) rats. Insulin-like growth factor 1 (IGF1) receptor (IGF1R) is important in promoting glucose metabolism in diabetes; however, the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear. In this study, a DM rat model was induced with high-fat diet feeding and streptozotocin (STZ) administration and rats were infused four times with HUcMSC. Blood glucose, interleukin-6 (IL-6), IL-10, glomerular basement membrane, and renal function were examined. Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays. The expression of IGF1R, phosphorylated checkpoint kinase 2 (p-CHK2), and phosphorylated protein 53 (p-p53) was examined using immunohistochemistry (IHC) and western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of 8-hydroxydeoxyguanosine (8-OHdG). Flow cytometry experiments were used to detect the surface markers of HUcMSC. The identification of the morphology and phenotype of HUcMSC was performed by way of oil red "O" staining and Alizarin red staining. DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane, increased the expression of IGF1 and IGF1R. IGF1R interacted with CHK2, and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells. When cisplatin was used to induce DNA damage, the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment. HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats. The expression of IGF1, IGF1R, p-CHK2, and p-p53, and the level of 8-OHdG in the DM group increased significantly compared with those in the control group, and decreased after HUcMSC treatment. Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage. HUcMSC infusion protected against kidney injury in DM rats. The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

An in vitro platform for quantifying cell cycle phase lengths in primary human intestinal epithelial cells.

The intestinal epithelium dynamically controls cell cycle, yet no experimental platform exists for directly analyzing cell cycle phases in non-immortalized human intestinal epithelial cells (IECs). Here, we present two reporters and a complete platform for analyzing cell cycle phases in live primary human IECs. We interrogate the transcriptional identity of IECs grown on soft collagen, develop two fluorescent cell cycle reporter IEC lines, design and 3D print a collagen press to make chamber slides for optimal imaging while supporting primary human IEC growth, live image cell cycle dynamics, then assemble a computational pipeline building upon free-to-use programs for semi-automated analysis of cell cycle phases. The PIP-FUCCI construct allows for assigning cell cycle phase from a single image of living cells, and our PIP-H2A construct allows for semi-automated direct quantification of cell cycle phase lengths using our publicly available computational pipeline. Treating PIP-FUCCI IECs with oligomycin demonstrates that inhibiting mitochondrial respiration lengthens G1 phase, and PIP-H2A cells allow us to measure that oligomycin differentially lengthens S and G2/M phases across heterogeneous IECs. These platforms provide opportunities for future studies on pharmaceutical effects on the intestinal epithelium, cell cycle regulation, and more.

Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease.

Population-level variation and mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized. We defined prototypical insulin secretion responses to three macronutrients in islets from 140 cadaveric donors, including those with type 2 diabetes. The majority of donors' islets exhibited the highest insulin response to glucose, moderate response to amino acid, and minimal response to fatty acid. However, 9% of donors' islets had amino acid responses, and 8% had fatty acid responses that were larger than their glucose-stimulated insulin responses. We leveraged this heterogeneity and used multi-omics to identify molecular correlates of nutrient responsiveness, as well as proteins and mRNAs altered in type 2 diabetes. We also examined nutrient-stimulated insulin release from stem cell-derived islets and observed responsiveness to fat but not carbohydrate or protein-potentially a hallmark of immaturity. Understanding the diversity of insulin responses to carbohydrate, protein, and fat lays the groundwork for personalized nutrition.

Silencing endomucin in bone marrow sinusoids improves hematopoietic stem and progenitor cell homing during transplantation.

Efficient homing of infused hematopoietic stem and progenitor cells (HSPCs) into the bone marrow (BM) is the prerequisite for successful hematopoietic stem cell transplantation. However, only a small part of infused HSPCs find their way to the BM niche. A better understanding of the mechanisms that facilitate HSPC homing will help to develop strategies to improve the initial HSPC engraftment and subsequent hematopoietic regeneration. Here, we show that irradiation upregulates the endomucin expression of endothelial cells in vivo and in vitro. Furthermore, depletion of endomucin in irradiated endothelial cells with short interfering RNA (siRNA) increases the HSPC-endothelial cell adhesion in vitro. To abrogate the endomucin of BM sinusoidal endothelial cells (BM-SECs) in vivo, we develop a siRNA-loaded bovine serum albumin nanoparticle for targeted delivery. Nanoparticle-mediated siRNA delivery successfully silences endomucin expression in BM-SECs and improves HSPC homing during transplantation. These results reveal that endomucin plays a critical role in HSPC homing during transplantation and that gene-based manipulation of BM-SEC endomucin in vivo can be exploited to improve the efficacy of HSPC transplantation.

Synovial mesenchymal stem cells secrete more lubricin than adipose mesenchymal stem cells after injection into rat osteoarthritis knees.

Intra-articular injection of mesenchymal stem cells (MSCs) is envisioned as a solution for knee osteoarthritis (OA). Although synovial MSCs (SyMSCs) are promising for cartilage regeneration, the clinical choice is usually adipose MSCs (AdMSCs). However, the similarities/differences in the mode of action between SyMSCs and AdMSCs remain unclear. Here, we compared factors secreted by human SyMSCs and AdMSCs after injection into OA knees. Human SyMSCs or AdMSCs were injected into the knees of rat partial meniscectomy models. The next day, the knee joints were collected to analyze the distribution of injected MSCs and transcriptome changes in the human MSCs and rat synovium. Non-injected MSCs were mixed with rat synovium as a control. After injection, no difference was apparent in intra-articular distribution of the SyMSCs or AdMSCs. RNA sequencing demonstrated an enrichment of cytokine-cytokine receptor interaction-related genes in both human SyMSCs and AdMSCs after injection. Differentially expressed genes (DEGs) specific to SyMSCs were associated with cartilage matrix synthesis and homeostasis. PCR analysis of the matrisome-related DEGs showed significantly higher expression of PRG4 in SyMSCs than in AdMSCs after injection. Immunostaining also confirmed a significantly greater expression of lubricin by SyMSCs than by AdMSCs. These findings indicate that SyMSCs will be a more promising treatment for OA.

Effects of the MCF-7 Exhausted Medium on hADSC Behaviour.

Stem cells possess the ability to differentiate into different lineages and the ability to self-renew, thus representing an excellent tool for regenerative medicine. They can be isolated from different tissues, including the adipose tissue. Adipose tissue and human adipose-derived stem cells (hADSCs) are privileged candidates for regenerative medicine procedures or other plastic reconstructive surgeries. The cellular environment is able to influence the fate of stem cells residing in the tissue. In a previous study, we exposed hADSCs to an exhausted medium of a breast cancer cell line (MCF-7) recovered at different days (4, 7, and 10 days). In the same paper, we inferred that the medium was able to influence the behaviour of stem cells. Considering these results, in the present study, we evaluated the expression of the major genes related to adipogenic and osteogenic differentiation. To confirm the gene expression data, oil red and alizarin red colorimetric assays were performed. Lastly, we evaluated the expression of miRNAs influencing the differentiation process and the proliferation rate, maintaining a proliferative state. The data obtained confirmed that cells exposed to the medium maintained a stem and proliferative state that could lead to a risky proliferative phenotype.

A network meta-analysis of the effectiveness of different basic preconditioning regiments in allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: To investigate and compare the effects of basic preconditioning regimens Bu/Cy, Cy/TBI and Flu/Bu for the treatment of patients in allogeneic hematopoietic stem cell transplantation. METHODS: It comprised exploring the published literature in the databases of PubMed, EMBASE, Cochrane Library, and Web of Science, using suitable keywords pertaining to various basic pretreatments Bu/Cy, Cy/TBI, and Flu/Bu, prior to allogeneic hematopoietic stem cell transplantation, and then extracting the searched outcome indicators of Overall Survival (OS) and survival (herein represented as OS and survival). Further, the results were estimated with meta-analysis using R, where the incidence of GVHD was reported in odds ratio (OR) with its 95% confidence interval (95%CI). RESULTS AND DISCUSSION: A total of 14 papers were included in this study, including 1436 cases were treated with Bu/Cy, 1816 cases with Cy/TBI, and 549 cases with Flu/Bu in the preconditioning regimen. After OS was the outcome pooled, compared with Flu/Bu in the preconditioning group, the results (Cy/TBI HR = 1.12 (95% Cl:1.04,1.61), Bu/Cy HR = 1.24 (95% Cl. 1.13,2.06)) showed that Flu/Bu preconditioning regimen significantly improved the overall survival rate of allogeneic HSCT patients. With the incidence of GVHD as the outcome summary, compared with Flu/Bu in the pretreatment group, the results (Cy/TBI HR = 1.24 (95% Cl:1.12, 1.82), Bu/Cy HR = 1.14 (95% Cl. 1.03, 2.12)) indicated that Flu/Bu in the pretreatment regimen group also significantly reduced the incidence of GVHD after allogeneic HSCT. CONCLUSION: Patients who received the basal preconditioning regimen Flu/Bu before allogeneic hematopoietic stem cell transplantation had the lowest hazard ratio for overall survival (OS) development. This indicates that the use of the basal preconditioning regimen Flu/Bu for the treatment of patients was the most effective, although the quality of the studies included needs to be confirmed by high-quality randomized controlled trials.

Case report: TP53 c.848G>A germline mutation as a possible screening target at initial diagnosis for acute lymphoblastic leukemia.

BACKGROUD: Li-Fraumeni syndrome is a hereditary tumor syndrome characterized by an elevated risk of malignancy, particularly acute lymphoblastic leukemia (ALL), which can be caused by the heterozygous germline mutation. TP53 gene germline mutation is considered a potential risk factor and crucial prognostic parameter for acute leukemia development and diagnosis, but rarely occurs in adults, and its specific pathogenic significance in acute leukemia is unclear. CASE PRESENTATION: We describes a case of a 45-year-old woman diagnosed with ALL. Whole-exome sequencing approach identified one of the TP53 germline mutations from her bone marrow sample with possible pathogenic significance, c.848G>A (p.Arg283His) heterozygous missense mutation located on exon 8, which was further verified in her hair, oral mucous and nail samples. Family pedigree screening revealed that the same TP53 genetic variant was present in the patient's father and non-donor son, whereas not in the donor. Digital PCR observed that this point mutation frequency dropped post-transplantation but remained low during maintenance therapy when the patient was leukemia-free. CONCLUSION: This suspected Li-Fraumeni syndrome case report with a likely pathogenic heterozygous TP53 variant expands the cancer genetic spectrum. Screening her family members for mutations facilitates identifying the optimal relative donor and avoids unnecessary treatment by monitoring TP53 germline mutations for minimal residual disease following hematopoietic stem cell transplantation. Its potential roles in hematological malignant tumor development and clinical pathogenic implications necessitate further probing.

Scalable Generation of 3D Pancreatic Islet Organoids from Human Pluripotent Stem Cells in Suspension Bioreactors.

We describe a scalable method for the robust generation of 3D pancreatic islet-like organoids from human pluripotent stem cells using suspension bioreactors. Our protocol involves a 6-stage, 20-day directed differentiation process, resulting in the production of 104-105 organoids. These organoids comprise α- and ß-like cells that exhibit glucose-responsive insulin and glucagon secretion. We detail methods for culturing, passaging, and cryopreserving stem cells as suspended clusters and for differentiating them through specific growth media and exogenous factors added in a stepwise manner. Additionally, we address quality control measures, troubleshooting strategies, and functional assays for research applications.

Comparison on the mechanism and potency of hepatotoxicity among hemp extract and its four major constituent cannabinoids.

Cannabidiol (CBD) has been reported to induce hepatotoxicity in clinical trials and research studies; however, little is known about the safety of other nonintoxicating cannabinoids. New approach methodologies (NAMs) based on bioinformatic analysis of high-throughput transcriptomic data are gaining increasing importance in risk assessment and regulatory decision-making of data-poor chemicals. In the current study, we conducted a concentration response transcriptomic analysis of hemp extract and its four major constituent cannabinoids [CBD, cannabichromene (CBC), cannabigerol (CBG), and cannabinol (CBN)] in hepatocytes derived from human induced pluripotent stem cells (iPSCs). Each compound impacted a distinctive combination of biological functions and pathways. However, all the cannabinoids impaired liver metabolism and caused oxidative stress in the cells. Benchmark concentration (BMC) analysis showed potencies in transcriptional activity of the cannabinoids were in the order of CBN > CBD > CBC > CBG, consistent with the order of their cytotoxicity IC50 values. Patterns of transcriptomic changes induced by hemp extract and its median overall BMC were very similar to CBD but differed significantly from other cannabinoids, suggesting that potential adverse effects of hemp extract were largely due to its major constituent CBD. Lastly, transcriptomic point-of-departure (tPoD) values were determined for each of the compounds, with the value for CBD (0.106µM) being concordant with a previously reported one derived from apical endpoints of clinical and animal studies. Taken together, the current study demonstrates the potential utility of transcriptomic BMC analysis as a NAM for hazard assessment of data-poor chemicals, improves our understanding of the possible health effects of hemp extract and its constituent cannabinoids, and provides important tPoD data that could contribute to inform human safety assessment of these cannabinoid compounds.

Autologous haematopoiesis stem cell transplantation (AHSCT) for treatment-refractory autoimmune diseases in children.

OBJECTIVES: To evaluate the long-term effectiveness and safety of autologous haematopoiesis stem cell transplantation (AHSCT) for severe, refractory autoimmune diseases in paediatric patients. METHODS: A single-centre study of consecutive children and adolescents with refractory autoimmune diseases undergoing AHSCT was performed. Demographics, clinical, laboratory features, pre-AHSCT medications, disease activity and functional status were captured. The primary outcome was progression-free survival, secondary outcomes included overall survival, disease-specific treatment responses, disease activity at the last follow-up and AHSCT safety. RESULTS: The study included seven patients: two systemic sclerosis, one pansclerotic morphoea, one eosinophilic fasciitis, one juvenile dermatomyositis and two patients with systemic juvenile idiopathic arthritis; four women, three men median age at AHSCT of 10 years (7-19), median follow-up post-AHSCT of 17 years. Median progression-free survival and overall survival was 4.2 years (95% CI: 0.98 to 8.3) and 17 years (95% CI: 11.8 to 22.1), respectively. Progression-free survival rates at 1 and 2 years post-AHSCT were 100% and 77%, respectively. All children survived. All patients are in clinical remission, only four require ongoing immunotherapy. SAFETY: Three experienced infections, including HHV6, Candida and Ralstonia sepsis; one developed a systemic inflammatory response syndrome; two new onset secondary autoimmune diseases including autoimmune haemolytic anaemia, Graves' disease and one was found to have a breast fibroadenoma. Treatment toxicity: one cyclophosphamide-associated transient renal failure and pericardial effusion, one patient with amenorrhoea/infertility. CONCLUSIONS: AHSCT was an effective and safe approach for children and adolescents with treatment-refractory autoimmune diseases. The indication and timing of transplantation requires a careful consideration and a multidisciplinary approach.

The molecular and cellular hematopoietic stem cell specification niche.

Hematopoietic stem cells (HSCs) are a population of tissue-specific stem cells that reside in the bone marrow of adult mammals where they self-renew and continuously regenerate the adult hematopoietic lineages over the life of the individual. Prominence as a stem cell model and clinical usefulness has driven interest in understanding the physiological processes that lead to specification of HSCs during embryonic development. High efficiency directed differentiation of HSCs by instruction of defined progenitor cells using sequentially defined instructive molecules and conditions remains impossible, indicating that comprehensive knowledge of the complete set of precursor intermediate identities and required inductive inputs remains incompletely understood. Recently, interest in the molecular and cellular microenvironment where HSCs are specified from endothelial precursors-the "specification niche"-has increased. Here we review recent progress in understanding these niche spaces across vertebrate phyla, as well as how a better characterization of the origin and molecular phenotypes of the niche cell populations has helped inform and complicate previous understanding of signaling required for HSC emergence and maturation.

Mobilization dynamics of bone marrow hematopoietic stem cells during hematopoietic regeneration.

Under stress hematopoiesis, previous studies have suggested the migration of hematopoietic stem cells (HSCs) from bone marrow (BM) to extramedullary sites such as spleen. However, there is little direct evidence of HSC migration from BM to spleen. Here, we induced myeloablation via 5-fluorouracil (5-FU) and showed the direct evidence of HSC migration from BM to spleen during hematopoietic regeneration via a photoconvertible fluorophore. Moreover, during steady-state, HSCs preferentially migrated to BM rather than spleen, but during hematopoietic regeneration HSCs preferred to spleen as a migration site equivalently or greater. Furthermore, in the early phase, HSCs egressed from BM through the attenuated HSC retention. However, HSCs in the late phase gained significantly enhanced cell-autonomous motility, which was independent of chemotaxis. Collectively, HSC mobilization from BM prior to the migration to spleen was dynamically changed from passive to active events during hematopoietic regeneration.

Glycogen myophosphorylase loss causes increased dependence on glucose in iPSC-derived retinal pigment epithelium.

Loss of glycogen myophosphorylase (PYGM) expression results in an inability to break down muscle glycogen, leading to McArdle disease-an autosomal recessive metabolic disorder characterized by exercise intolerance and muscle cramps. While previously considered relatively benign, this condition has recently been associated with pattern dystrophy in the retina, accompanied by variable sight impairment, secondary to retinal pigment epithelial (RPE) cell involvement. However, the pathomechanism of this condition remains unclear. In this study, we generated a PYGM-null induced pluripotent stem cell (iPSC) line, and differentiated it into mature RPE to examine structural and functional defects, along with metabolite release into apical and basal media. Mutant RPE exhibited normal photoreceptor outer segment phagocytosis but displayed elevated glycogen levels, reduced transepithelial resistance, and increased cytokine secretion across the epithelial layer compared to isogenic wildtype controls. Additionally, decreased expression of the visual cycle component, RDH11, encoding 11-cis-retinol dehydrogenase, was observed in PYGM-null RPE. While glycolytic flux and oxidative phosphorylation levels in PYGM-null RPE were near normal, the basal oxygen consumption rate (OCR) was increased. OCR in response to physiological levels of lactate was significantly greater in wildtype compared to PYGM-null RPE. Inefficient lactate utilization by mutant RPE resulted in higher glucose dependence and increased glucose uptake from the apical medium in the presence of lactate, suggesting a reduced capacity to spare glucose for photoreceptor use. Metabolic tracing confirmed slower 13C-lactate utilization by PYGM-null RPE. These findings have key implications for retinal health since they likely underlie the vision impairment in individuals with McArdle disease.

Reduction of Oxidative Stress and Excitotoxicity by Mesenchymal Stem Cell Biomimetic Co-Delivery System for Cerebral Ischemia-Reperfusion Injury Treatment.

A cerebral ischemia-reperfusion injury is ensued by an intricate interplay between various pathological processes including excitotoxicity, oxidative stress, inflammation, and apoptosis. For a long time, drug intervention policies targeting a single signaling pathway have failed to achieve the anticipated clinical efficacy in the intricate and dynamic inflammatory environment of the brain. Moreover, inadequate targeted drug delivery remains a significant challenge in cerebral ischemia-reperfusion injury therapy. In this study, a multifunctional nanoplatform (designated as PB-006@MSC) is developed using ZL006-loaded Prussian blue nanoparticles (PBNPs) camouflaged by a mesenchymal stem cell (MSC) membrane (MSCm). ZL006 is a neuroprotectant. It can be loaded efficiently into the free radical scavenger PBNP through mesoporous adsorption. This can simultaneously modulate multiple targets and pathways. MSCm biomimetics can reduce the nanoparticle immunogenicity, efficiently enhance their homing capability to the cerebral ischemic penumbra, and realize active-targeting therapy for ischemic stroke. In animal experiments, PB-006@MSC integrated reactive oxygen species (ROS) scavenging and neuroprotection. Thereby, it selectively targeted the cerebral ischemic penumbra (about fourfold higher accumulation at 24 h than in the non-targeted group), demonstrated a remarkable therapeutic efficacy in reducing the volume of cerebral infarction (from 37.1% to 2.3%), protected the neurogenic functions, and ameliorated the mortality.

[Comparison of etoposide combined with G-CSF and cyclophosphamide combined with G-CSF in the mobilization of autologous peripheral blood stem cells in patients with multiple myeloma].

Objective: The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Methods: Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. Results: ①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg vs 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) (P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg (P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d (P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d (P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion: The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.