Injection Of Cells Research Articles

Survival impact of [225Ac]Ac-DOTATOC alpha-therapy in a preclinical model of pancreatic neuroendocrine tumor liver micrometastases.

A mouse model of liver metastases of pancreatic NETs was developed by intraportal injection of AR42J cells and explored using [68Ga]Ga-DOTATOC and [18F]F-FDG PET/MRI. Biodistribution study and radiation dosimetry of [225Ac]Ac-DOTATOC were determined in subcutaneous tumor-bearing NMRI-nude mice. Efficacy and toxicity were determined by intravenous injection of increasing activities of [225Ac]Ac-DOTATOC 10days after intraportal graft. Liver tumors showed a high uptake of [68Ga]Ga-DOTATOC and no uptake of [18F]F-FDG confirming the well-differentiated phenotype. All groups treated with [225Ac]Ac-DOTATOC showed a significant increase in overall survival compared with DOTATOC-treated mice, especially those treated with the highest activities: 53days with 240kBq (p = 0.0001), and 58days with 2 × 120kBq (p < 0.0001) vs 28days with non-radiolabeled DOTATOC. On blood tests, a transient and moderate decreased in white blood cells count after treatment and no severe hepatic or renal toxicity were observed after treatment which was consistent with pathological and radiation dosimetry findings. [225Ac]Ac-DOTATOC exhibit a favorable efficacy and toxicity profile in a mouse model of liver micrometastatic pancreatic NET.

Pharmacological Treatments for Erectile Dysfunction in Diabetic Patients: Efficacy, Safety, and Emerging Therapies

Men with diabetes mellitus, particularly those with type 2 diabetes (T2DM), are known to experience erectile dysfunction (ED), a condition whose prevalence has risen to 75% in recent years. The pathophysiology of ED in diabetic patients involves vascular impairment, neuropathy, hormonal dysregulation, and chronic hyperglycemia, all of which contribute to endothelial dysfunction, reduced nitric oxide availability, and nerve damage. Phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil, are the first-line pharmacological treatments for ED, though their efficacy is reduced in diabetic patients due to the extent of vascular and neurological damage. Other treatments, including testosterone replacement therapy (TRT), intracavernosal injections, and vacuum erection devices (VEDs), provide alternatives for patients unresponsive to PDE5 inhibitors. Emerging therapies such as low-intensity extracorporeal shockwave therapy (LI-ESWT) and regenerative medicine approaches, including stem cell and platelet-rich plasma (PRP) injections, show potential in improving erectile function in diabetic patients. Glycemic control plays a critical role in both preventing ED and enhancing the efficacy of treatments by improving vascular function and reversing nerve damage. This review was conducted through an extensive analysis of current literature on pharmacological and emerging treatments for ED in diabetic patients. In conclusion, integrating traditional pharmacotherapy with emerging treatments and emphasizing glycemic control holds promise for optimizing ED management in diabetic patients. Keywords: Erectile Dysfunction (ED), Diabetes Mellitus (T2DM), Phosphodiesterase Type 5 (PDE5) Inhibitors, Testosterone Replacement Therapy (TRT), Glycemic Control

Functional outcome of the anterior vaginal wall in a pelvic surgery injury rat model after treatment with stem cell-derived progenitors of smooth muscle cells

BackgroundStem-cell-derived therapy is a promising option for tissue regeneration. Human iPSC-derived progenitors of smooth muscle cells (pSMCs) exhibit limited proliferation and differentiation, which minimizes the risk of tumor formation while restoring smooth muscle cells (SMCs). Up to 29% of women suffer from recurrence of vaginal prolapse after prolapse surgery. Therefore, there is a need for therapies that can restore vaginal function. SMCs contribute to vaginal tone and contractility. We sought to examine whether human pSMCs can restore vaginal function in a rat model.MethodsFemale immunocompromised RNU rats were divided into 5 groups: intact controls (n = 12), VSHAM (surgery + saline injection, n = 35), and three cell-injection groups (surgery + cell injection using pSMCs from three patients, n = 14/cell line). The surgery to induce vaginal injury was analogous to prolapse surgery. Menopause was induced by surgical ovariectomy. The vagina, urethra, bladder were harvested 10 weeks after surgery (5 weeks after cell injection). Organ bath myography was performed to evaluate the contractile function of the vagina, and smooth muscle thickness was examined by tissue immunohistochemistry. Collagen I, collagen III, and elastin mRNA and protein expressions in tissues were assessed.ResultsVaginal smooth muscle contractions induced by carbachol and KCl in the cell-injection groups were significantly greater than those in the VSHAM group. Collagen I protein expression in the vagina of the cell-injections groups was significantly higher than in the VSHAM group. Vaginal elastin protein expression was similar between the cell-injection and VSHAM groups. In the urethra, gene expression levels of collagen I, III, and elastin were all significantly greater in the cell-injection groups than in the VSHAM group. Collagen I, III, and elastin protein expression of the urethra did not show a consistent trend between cell-injection groups and the VSHAM group.ConclusionsHuman iPSC-derived pSMCs transplantation appears to be associated with improved contractile function of the surgically injured vagina in a rat model. This is accompanied by changes in extracellular protein expression the vagina and urethra. These observations support further efforts in the translation of pSMCs into a treatment for regenerating the surgically injured vagina in women who suffer recurrent prolapse after surgery.

Adipose-Derived Stem Cell Therapy in Spinal Cord Injury.

Spinal cord injury (SCI) is a serious condition accompanied by severe adverse events that affect several aspects of the patient's life, such as motor, sensory, and functional impairment. Despite its severe consequences, definitive treatment for these injuries is still missing. Therefore, researchers have focused on developing treatment strategies aimed at ensuring full recovery post-SCI. Accordingly, attention has been drawn toward cellular therapy using mesenchymal stem cells. Considering their wide availability, decreased immunogenicity, wide expansion capacity, and impressive effectiveness in many therapeutic approaches, adipose-derived stem cell (ADSC) injections in SCI cases have been investigated and showed promising results. In this review, SCI pathophysiology and ADSC transplantation benefits are discussed independently, together with SCI animal models and adipose stem cell preparation and application techniques. The mechanisms of healing in an SCI post-ADSC injection, the outcomes of this therapeutic approach, and current clinical trials are also deliberated, in addition to the challenges and future perspectives, aiming to encourage further research in this field.

Phase I study of safety and efficacy of allogeneic natural killer cell therapy in relapsed/refractory neuroblastomas post autologous hematopoietic stem cell transplantation

Despite low incidence, neuroblastoma, an immunologically cold tumor, is the most common extracranial solid neoplasm in pediatrics. In relapsed/refractory cases, the benefits of autologous hematopoietic stem cell transplantation (auto-HSCT) and other therapies are limited. Natural killer (NK) cells apply cytotoxicity against tumor cells independently of antigen-presenting cells and the adaptive immune system. The primary endpoint of this trial was to assess the safety of the injection of allogenic, ex vivo-expanded and primed NK cells in relapsed/refractory neuroblastoma patients after auto-HSCT. The secondary endpoint included the efficacy of this intervention in controlling tumors. NK cells were isolated and primed ex vivo (by adding interleukin [IL]-2, IL-15, and IL-21) in a GMP-compliant CliniMACS system and administered to four patients with relapsed/refractory MYCN-positive neuroblastoma. NK cell injections (1 and 5 × 107 cells/kg in the first and second injections, respectively) were safe, and no acute or sub-acute adverse events were observed. During the follow-up period, one complete response (CR) and one partial response (PR) were observed, while two cases exhibited progressive disease (PD). In follow-up evaluations, two died due to disease progression, including the case with a PR. The patient with CR had regular growth at the 31-month follow-up, and another patient with PD is still alive and receiving chemotherapies 20 months after therapy. This therapy is an appealing and feasible approach for managing refractory neuroblastomas post-HSCT. Further studies are needed to explore its efficacy with higher doses and more frequent administrations for high-risk neuroblastomas and other immunologically cold tumors.Trial registration number: irct.behdasht.gov.ir (Iranian Registry of Clinical Trials, No. IRCT20201202049568N1).

Investigation of the Frequency of Reactions and Consequences of Blood Transfusion in an Academic Center Guilan-Iran

Background: Blood transfusion is a life-saving procedure, but there are always potential risks, such as blood transfusion reactions. Objectives: Considering the importance of the subject and the lack of a similar study in Guilan province, this research was conducted to analyze blood transfusion reactions. Methods: This retrospective descriptive study was conducted at Al-Zahra Hospital in Guilan, Iran, between 2020 and 2022. The files of all patients who received blood products at this center and experienced a reaction were reviewed. A checklist was completed, which included details such as the hospital ward, age, blood group, underlying disease, type of surgery, type of injected product, history of transfusion, history of reaction and allergy, type of reaction, and treatment intervention. Results: During the study period, 4,887 cases received transfusions. Among them, 18 cases (0.36%) showed reactions during transfusion, of which 14 cases (0.35% of total packed cell injections) were related to packed cell injection. Shivering was the most common reaction, occurring in 8 cases (15.38%). The main interventions included the administration of steroids in 10 cases (25%), antihistamines in 7 cases (17.5%), and oxygen therapy in 7 cases (17.5%). Three cases (7.5%) were transferred to the ICU, and in three cases (7.5%), the blood transfusion was stopped. One mortality was reported, and no cases of incompatible blood transfusion were documented. Conclusions: The incidence of reactions to blood product injections at this center appears to be acceptable. However, it was found that the information recording systems were very inefficient, and forms were incompletely filled, which should be addressed and corrected.

Knockdown of HSPA13 Inhibits TGFβ1-Induced Epithelial-Mesenchymal Transition of RPE by Suppressing the PI3K/Akt Signaling Pathway.

This study aimed to explore the impact of HSPA13 on epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells and proliferative vitreoretinopathy (PVR) development, along with its associated molecular mechanisms. HSPA13 expression was evaluated in epiretinal membranes (ERMs) from patients with PVR using immunohistochemistry. The effects of HSPA13 knockdown on TGFβ1-induced EMT in hESC-RPE cells were studied through quantitative PCR (qPCR), Western blot, and wound healing assays. Intracellular Ca2+ levels were measured using Fluo-8/AM incubation. A rat PVR model was induced by the intravitreal injection of RPE cells combined with platelet-rich plasma (PRP). RNA-seq was applied to study the molecular mechanism of HSPA13 knockdown-mediated EMT inhibition. HSPA13 was found in human ERMs and its expression increased with TGFβ1 treatment in hESC-RPE cells. Knockdown of HSPA13 inhibited TGFβ1-induced EMT and migration. In the PVR rat model, HSPA13 was expressed in the ERMs and its knockdown in RPE cells reduced the development of PVR. Consistent with these observations, RNA-seq showed a global suppression of TGFβ1-induced EMT and migration by shHSPA13 in RPE cells. Mechanistically, TGFβ1 treatment increased intracellular Ca2+ levels, leading to an upregulation of HSPA13 expression. Downregulation of HSPA13 hindered the phosphorylation of PI3K/Akt in TGFβ1-induced RPE cells. Our study revealed the involvement of HSPA13 in PVR development, as well as in TGFβ1-induced EMT of RPE through the PI3K/Akt signaling pathway. Targeting HSPA13-related pathways involved in regulating EMT in RPE cells could serve as a novel therapeutic approach for patients with PVR.

Closing the internal opening with a rectal advancement flap increases the efficacy of mesenchymal stem cell injection for complex Crohn's disease anal fistulas.

The efficacy of injections of mesenchymal stem cells (MSC) for anal fistula treatment may be impaired by the persistence of stools passing into the fistula, causing bacterial contamination and a local inflammatory reaction. We aimed to compare remission rates between patients treated by MSC injection with simple sutures and those treated with a rectal advancement flap. This single-center prospective study compared the first patients who underwent internal opening closure with sutures with the subsequent patients treated with a flap. Complete clinical remission was defined as complete closure of the external opening(s) without pain or discharge, and complete radiological remission was defined as a Magnifi-CD score of 0. We compared the first 42 patients who had sutures with the 20 subsequent patients who had an advancement flap. The median follow-up was 15.5 [8.8-24.9]months. The cumulative incidence of complete clinical response at M12 was 53.8% [38.1-69.6%] in the suture group versus 93.3% [77.4-100.0] in the flap group (p < 0.001). The Magnifi-CD score was 0 for 41.7% [25.5-59.2%]) of patients treated with sutures versus 72.7% [39.0-63.9%]) of patients treated with a flap (p=0.093). Anal incontinence score did not differ between the two groups. Practicing an advancement flap was the only significant factor associated with complete clinical remission over time (adjusted HR [95% CI] of 2.6 [1.4-4.9], p = 0.003). Complete clinical remission rates following MSC injection are significantly higher after closure of the internal opening with a rectal flap than after closure with sutures, without consequences on anal continence.

Tryptophan 2,3-dioxygenase-positive matrix fibroblasts fuel breast cancer lung metastasis via kynurenine-mediated ferroptosis resistance of metastatic cells and T cell dysfunction.

Tumor metastasis is a major threat to cancer patient survival. The organ-specific niche plays a pivotal role in tumor organotropic metastasis. Fibroblasts serve as a vital component of the metastatic microenvironment, but how heterogeneous metastasis-associated fibroblasts (MAFs) promote organotropic metastasis is poorly characterized. Here, we aimed to decipher the heterogeneity of MAFs and elucidate the distinct roles of these fibroblasts in pulmonary metastasis formation in breast cancer. Mouse models of breast cancer pulmonary metastasis were established using an in vivo selection method of repeated injections of metastatic cells purified from the mouse lung. Single-cell RNA-sequencing (scRNA-seq) was employed to investigate the heterogeneity of MAFs. Transgenic mice were used to examine the contribution of tryptophan 2,3-dioxygenase-positive matrix fibroblasts (TDO2+ MFs) in lung metastasis. We uncovered 3 subtypes of MAFs in the lung metastatic microenvironment, and their transcriptome profiles changed dynamically as lung metastasis evolved. As the predominant subtype, MFs were exclusively marked by platelet-derived growth factor receptor alpha (PDGFRA) and mainly located on the edge of the metastasis, and T cells were enriched around MFs. Notably, high MF signatures were significantly associated with poor survival in breast cancer patients. Lung metastases were markedly diminished, and the suppression of T cells was dramatically attenuated in MF-depleted experimental metastatic mouse models. We found that TDO2+ MFs controlled pulmonary metastasis by producing kynurenine (KYN), which upregulated ferritin heavy chain 1 (FTH1) level in disseminated tumor cells (DTCs), enabling DTCs to resist ferroptosis. Moreover, TDO2+ MF-secreted chemokines C-C motif chemokine ligand 8 (CCL8) and C-C motif chemokine ligand 11 (CCL11) recruited T cells. TDO2+ MF-derived KYN induced T cell dysfunction. Conditional knockout of Tdo2 in MFs diminished lung metastasis and enhanced immune activation. Our study reveals crucial roles of TDO2+ MFs in promoting lung metastasis and DTCs' immune evasion in the metastatic niche. It suggests that targeting the metabolism of lung-specific stromal cells may be an effective treatment strategy for breast cancer patients with lung metastasis.

Mucosal-associated invariant T cells modulate innate immune cells and inhibit colon cancer growth.

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions and have potentials for use as adoptive cell therapy. However, studies into their anti-cancer activity, including their role in colon cancer, are limited. Using an animal model of colon cancer, we showed that peritumoral injection of invivo-expanded MAIT cells into RAG1-/- mice with MC38-derived tumours inhibits tumour growth compared to control. Multiplex cytokine analyses showed that tumours from the MAIT cell-treated group have higher expression of markers for eosinophil-activating cytokines, suggesting a potential association between eosinophil recruitment and tumour inhibition. In a human peripheral leukocyte co-culture model, we showed that leukocytes stimulated with MAIT ligand showed an increase in eotaxin-1 production and activation of eosinophils, associated with increased cancer cell killing. In conclusion, we showed that MAIT cells have a protective role in a murine colon cancer model, associated with modulation of the immune response to cancer, potentially involving eosinophil-associated mechanisms. Our results highlight the potential of MAIT cells for non-donor restricted colon cancer immunotherapy.

442O A phase I clinical trial of intrathecal injection of allogeneic CAR-γδT cells targeting B7H3 for the treatment of patients with recurrent glioblastoma

442O A phase I clinical trial of intrathecal injection of allogeneic CAR-γδT cells targeting B7H3 for the treatment of patients with recurrent glioblastoma

Emerging alternatives to keratoplasty for corneal endothelial cell dysfunction.

While effective for treating endothelial dysfunction, keratoplasty has shortcomings including limited access to donor tissue for much of the world. Thus, alternative strategies are under development. This review explores the main advancements achieved in this field during 2022-2023. Recent publications further support the validity of intracameral cultivated allogeneic endothelial cell injection and Descemet stripping only, while emphasizing the benefits of adjunctive Rho-associated kinase inhibitor (ROCKi) therapy. New donor-independent artificial implants, such as EndoArt, show favorable results. Multiple pharmacologic agents, especially ROCKi, show promise as monotherapies, yet none are currently approved for human treatment. Multiple regenerative and genetic therapies are being investigated but all are still in preclinical stages. A plethora of innovative alternatives to keratoplasty for endothelial disease is in development. Among these, surgical methods are still the mainstay of treatment and closest to clinical application, though further studies to establish their benefits over keratoplasty are needed. Albeit promising, pharmacologic, regenerative, and genetic approaches require validation and are farther from clinical application.

Efficacy and safety of mesenchymal stem cell injections for knee osteoarthritis: A systematic review and meta-analysis

Background: There have not been any clear studies on the use of mesenchymal stem cells (MSCs) to treat osteoarthritis (OA) in the knee. Materials and Methods: This study investigates the effects of different MSC dosages on pain alleviation in individuals with OA in the knee by conducting a meta-analysis of existing randomized controlled trials. Electronic resources such as Google Scholar, PubMed, Cochrane Library, and Web of Science were searched up until June 2023. Treatment effect sizes were computed using the knee osteoarthritis outcome score (KOOS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Knee Society Score (KSS). Random or fixed effect models were applied to aggregate the data. We performed a subgroup analysis according to dosage level. The heterogeneity of the research was investigated using the Chi-square test and the I2 index. Results: The meta-analysis included 26 studies with a total sample size of 739 patients. A significant reduction in pain was observed 1 year and 2 years following the injection of MSCs into the injured joint, as indicated by the Visual Analogue Scale, WOMAC, KOOS, and KSS indexes (P &lt; 0.05). Patients on MSCs reported much reduced pain after 1 and 2 years compared to the control group (P &lt; 0.05). Subgroup and meta-regression analyses revealed no statistically significant variations in the effectiveness of MSC dosage (P &lt; 0.05). The studies did not report any adverse effects. Conclusion: Different dosages of MSCs had the same pain-relieving effects on patients with OA in the knee. MSC injections were safe and beneficial in such cases.

Epigenetic Regulation of RNF135 by LSD1 Promotes Stemness Maintenance and Brain Metastasis in LungAdenocarcinoma.

RING finger protein 135 (RNF135) is identified as a regulator in certain cancer types. However, its role and molecular mechanisms in lung adenocarcinoma (LUAD) are still unclear. Herein, we investigated the level of RNF135 in tumor tissues of LUAD patients using the UALCAN database and confirmed the data by real-time PCR and western blot analysis. The effects of RNF135 on stemness maintenance and migration/invasion capability of LUAD cells were investigated by sphere formation, flow cytometry, wound healing, and transwell assay. Limiting dilution xenograft assay and intracardiac injection of LUAD cells were applied to assess the implications of RNF135 in tumorigenesis and brain metastasis. Our results revealed that RNF135 was upregulated in tumor tissues of LUAD patients and was positively correlated with poor prognosis. Knockdown of RNF135 suppressed cancer stem cells (CSCs)-like properties, and migration/invasion capability of A549 and NCI-H1975 cells. Conversely, overexpression of RNF135 augmented CSCs-like traits and migration/invasion ability of LUAD cells. Limiting dilution xenograft assay demonstrated that RNF135 was required for the self-renewal of CSCs to initiate LUAD development. Overexpression of RNF135 in A549 cells increased their ability to metastasize to the brain in vivo. Mechanistically, the transcriptional activation of RNF135 by LSD1 involved H3K9me2 demethylation at the promoter region of RNF135. Reexpression of RNF135 in LSD1-silenced A549 cells was able to reverse LSD1-mediated stemness maintenance and migration/invasion capability. Overall, our results implied that targeting of LSD1/RNF135 axis might be a feasible method to suppress tumorigenesis and brain metastasis of LUAD patients.

Downregulation of malic enzyme 3 facilitates progression of gastric carcinoma via regulating intracellular oxidative stress and hypoxia-inducible factor-1α stabilization

BackgroundGastric cancer (GC) is one of the most malignant cancers worldwide. Metabolism disorder is a critical characteristic of malignant tumors related to tumor progression and metastasis. However, the expression and molecular mechanism of malic enzyme 3 (ME3) in GC are rarely reported. In this study, we aim to investigate the molecular mechanism of ME3 in the development of GC and to explore its potential value as a prognostic and therapeutic target in GC.MethodME3 mRNA and protein expression were evaluated in patients with GC using RT-qPCR, WB, and immunohistochemistry, as well as their correlation with clinicopathological indicators. The effect of ME3 on proliferation and metastasis was evaluated using Cell Counting Kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU) assay, transwell assay, wound healing assay, and subcutaneous injection or tail vein injection of tumor cells in mice model. The effects of ME3 knockdown on the level of metabolites and hypoxia-inducible factor-1α (HIF-1α) protein were determined in GC cells. Oxidative phosphorylation was measured to evaluate adenosine triphosphate (ATP) production.ResultsME3 was downregulated in human GC tissues (P < 0.001). The decreased ME3 mRNA expression was associated with younger age (P = 0.02), pathological staging (P = 0.049), and lymph node metastasis (P = 0.001), while low ME3 expression was associated with tumor size (P = 0.048), tumor invasion depth (P < 0.001), lymph node metastasis (P = 0.018), TNM staging (P < 0.001), and poor prognosis (OS, P = 0.0206; PFS P = 0.0453). ME3 knockdown promoted GC cell malignancy phenotypes. Moreover, α-ketoglutarate (α-KG) and NADPH/NADP+ ratios were reduced while malate was increased in the ME3 knockdown group under normoxia. When cells were incubated under hypoxia, the NADPH/NADP+ ratio and α-KG decreased while intracellular reactive oxygen species (ROS) increased significantly. The ME3 knockdown group exhibited an increase in ATP production and while ME3 overexpression group exhibited oppositely. We discovered that ME3 and HIF-1α expression were negatively correlated in GC cells and tissues, and proposed the hypothesis: downregulation of ME3 promotes GC progression via regulating intracellular oxidative stress and HIF-1α.ConclusionWe provide evidence that ME3 downregulation is associated with poor prognosis in GC patients and propose a hypothesis for the ME3 regulatory mechanism in GC progression. The present study is of great scientific significance and clinical value for exploring the prognostic and therapeutic targets of GC, evaluating and improving the clinical efficacy of patients, reducing recurrence and metastasis, and improving the prognosis and quality of life of patients.

Tissue-engineered sub-urethral sling with muscle-derived cells for urethral sphincter regeneration in an animal model of stress urinary incontinence.

Stress urinary incontinence (SUI) is a widespread condition affecting more than 200 million people worldwide. Common treatments for this condition include retropubic colposuspension, and pelvic sling methods, which use autologous grafts or synthetic materials to support the bladder neck and urethral sphincter. Although these treatments have a cure rate of over 80%, adverse effects and recurrence may still occur. Several studies have focused on the potential of cell therapy. Muscle-derived cells (MDCs) can be easily obtained from small biopsied striated muscular tissues and possess superior multi-lineage differentiation and self-renewal capacity. Based on the unique characteristics of MDCs and previous favorable results in muscle regeneration, we fabricated a chitosan-gelatin hydrogel sling loaded with MDCs in a rat model of SUI. Leak point pressure and histological indices regarding inflammation, muscular atrophy, and collagen density were assessed to compare the effectiveness of cell injection and cell-laden sling. The level of LPP was significantly reduced in the MODEL group versus the control animals. The LPP level was considerably higher in CELL INJECTION, SLING, and CELL/SLING groups compared to the MODEL group but did not reach the significance threshold. The inflammation rate was significantly lower in the CELL/SLING group compared to the SLING group. The CELL/SLING group showed less atrophy compared to the other experimental groups, indicating that the cells may have higher viability on SLING than through injection. This also suggests that in long-term studies, as the degradation rate of hydrogels increases, the function of cells will become more apparent.

Intravenous injection of allogenic canine mesenchymal stem cells in 40 client-owned dogs: a safety assessment in veterinary clinical trials

BackgroundThe aim of this study was to evaluate the adverse effects of allogeneic mesenchymal stem cells (MSCs) transplanted via intravenous infusion in dogs and examine their safety. We performed a retrospective analysis of various clinical assessments, including physical examination, blood tests, and radiographs, and monitored the formation of neoplasms during a 6-month follow-up period in 40 client-owned dogs that received intravenous infusion of adipose tissue-derived MSCs (AT-MSCs) for the treatment of various underlying diseases between 2012 and 2018.ResultsNo significant adverse effects of MSC therapy were detected by clinical assessment, blood tests, or radiographic examination in the 6-month follow-up period after the first MSC treatment. Additionally no new neoplasms were observed during this period.ConclusionsTo our knowledge, this study is the first to evaluate the safety aspects (≥ 6 months) associated with intravenous allogeneic AT-MSC infusion. These results suggest that allogenic AT-MSC infusion could be a useful and relatively safe therapeutic approach in canines.

Curcumin suppresses copper accumulation in non-small cell lung cancer by binding ATOX1

BackgroundNon-small cell lung cancer (NSCLC) is associated with intracellular copper accumulation. Antioxidant 1 (ATOX1) is a copper chaperone. This study aimed to analyze the anti-cancer effects of curcumin on the ATOX1-mediated copper pathway in NSCLC.MethodsA binding activity between curcumin and ATOX1 was measured using molecular docking. NSCLC cells, A549 and H1299, were treated with different doses of curcumin (10, 20, 40 µM) or DC-AC50 (5, 10, 20 µM) for 24 h. The cell viability and levels of ATOX1, ATP7A and COX17 proteins were observed in cells. Overexpressing ATOX1 in cells was established by pcDNA3.1-ATOX1 transfection for 24 h. The ATOX1 overexpressing cells were treated with 40 µM curcumin or 20 µM DC-AC50 for 24 h to analyze the mechanism of curcumin in NSCLC treatment. Cell viability was measured by CCK-8, and levels of proteins were measured by western blotting. The copper level in cells was labeled by copper sensor-1. Moreover, nude mice models were induced by injection of A549 cells and treated with 20 mg/kg/d DC-AC50 or 40 mg/kg/d curcumin. Tumor growth was observed by measuring tumor volume and tumor weight. The levels of ATOX1, ATP7A and COX17 in tumors were measured by immunohistochemistry and western blotting.ResultsCurcumin bound to ATOX1 (score = −6.1 kcal/mol) and decreased the levels of ATOX1, ATP7A and COX17 proteins in NSCLC cells. The curcumin or DC-AC50 treatment suppressed cell viability by inhibiting the ATOX1-mediated copper signaling in NSCLC cells. The ATOX1 overexpression in cells significantly weakened the effects of curcumin on suppressing copper accumulation and the ATOX1-mediated copper pathway (p < 0.05). In mice models, curcumin or DC-AC50 treatment also suppressed tumor growth by suppressing the ATOX1-mediated copper pathway in tumors.ConclusionThis study demonstrated that curcumin bound ATOX1 to suppress copper accumulation in NSCLC cells, providing a new mechanism of curcumin for NSCLC treatment.

New Endoscopic Devices and Techniques for the Management of Post-Sleeve Gastrectomy Fistula and Gastric Band Migration.

Post-sleeve gastrectomy fistulas are a rare but possibly severe life-threatening complication. Besides early reoperation and drainage, endoscopy is the main treatment option. According to the clinical setting, endoscopic treatment options comprise stent or clip placement. New endoscopic therapies have recently gained attention, including endoscopic vacuum therapy, VacStent therapy, endoscopic internal drainage with pigtail stents, endoscopic suturing and stem cell injection. In this narrative review, we shed light on recent literature, developments, indications and contraindications of these treatments. Intragastric gastric band migration is a rare complication after gastric band positioning. Reoperation can sometimes be difficult, especially when a gastric band has already migrated far into the stomach. Endoscopic retrieval can be a valid, non-invasive therapeutic solution. We reviewed the current literature on this matter.

Management of Red Cell Alloimmunization in Pregnancy.

Rhesus immune globulin has resulted in a marked decrease in the prevalence of RhD alloimmunization in pregnancy; however, antibody formation to other red cell antigens continues to occur. Evaluation for the presence of anti-red cell antibodies should be routinely undertaken at the first prenatal visit. If anti-red cell antibodies are detected, consideration of a consultation or referral to a maternal-fetal medicine specialist with experience in the monitoring and treatment of these patients is warranted. Cell-free DNA can be used to determine fetal red cell antigen status to determine whether the pregnancy is at risk of complications from the red cell antibodies. First-time sensitized pregnancies are followed up with serial maternal titers, and, when indicated, serial Doppler assessment of the peak systolic velocity in the middle cerebral artery should be initiated by 16 weeks of gestation. When there is a history of an affected fetus or neonate, maternal titers are less predictive of fetal risk; if the fetus is antigen positive, serial peak systolic velocity in the middle cerebral artery measurements should be initiated by 15 weeks of gestation because intraperitoneal intrauterine blood transfusions can be used at this gestation if needed. The mainstay of fetal therapy involves intrauterine transfusion through ultrasound-directed puncture of the umbilical cord with the direct intravascular injection of red cells. A perinatal survival rate exceeding 95% can be expected at experienced centers. Neonatal phototherapy and "top-up" transfusions attributable to suppressed reticulocytosis often are still required for therapy after delivery.