Differentiation Induction of Mesenchymal Stem Cells by a Au Delivery Platform.

Au decorated with type I collagen (Col) was used as a core material to cross-link with stromal cell-derived factor 1α (SDF1α) in order to investigate biological performance. The Au-based nanoparticles were subjected to physicochemical determination using scanning electron microscopy (SEM), dynamic light scattering (DLS) and ultraviolet-visible (UV-Vis) and Fourier-transform infrared spectroscopy (FTIR). Mesenchymal stem cells (MSCs) were used to evaluate the biocompatibility of this nanoparticle using the MTT assay and measuring reactive oxygen species (ROS) production. Also, the biological effects of the SDF-1α-conjugated nanoparticles (Au-Col-SDF1α) were assessed and the mechanisms were explored. Furthermore, we investigated the cell differentiation-inducing potential of these conjugated nanoparticles on MSCs toward endothelial cells, neurons, osteoblasts and adipocytes. We then ultimately explored the process of cell entry and transportation of the nanoparticles. Using a mouse animal model and retro-orbital sinus injection, we traced in vivo biodistribution to determine the biosafety of the Au-Col-SDF1α nanoparticles. In summary, our results indicate that Au-Col is a promising drug delivery system; it can be used to carry SDF1α to improve MSC therapeutic efficiency.

Optimizing tumor-associated antigen-stimulated autologous dendritic cell and cytokine-induced killer cell coculture to enhance cytotoxicity for cancer immunotherapy in manufacturing.

BACKGROUND: Dendritic Cell Cytokine-induced killer cell (DC-CIK) coculture treatment in cancer immunotherapy has been shown to be effective. However, the cost of DC- CIK therapy is prohibitive for many patients, and the lack of standard manufacturing processes and treatment strategies are major limitations. Our study used tumor lysate as a tumor-associated antigen source and DCs and CIK cells in coculture. We developed an efficient method to obtain autologous DCs- and CIK cells from peripheral blood. We used flow cytometry to assess DC activation and the cytometric bead array assay to quantify cytokines secreted by CIK cells. RESULTS: We evaluated the antitumor activity of DC- CIK coculture in vitro with the K562 cell line. We demonstrated that a manufacturing process employing frozen immature DCs can yield the lowest loss with the highest economic benefits. DC-CIK coculture can effectively upgrade CIK cells' immunological specificity to tumors in the presence of tumor-associated antigens. CONCLUSION: In vitro experiments revealed that when the DC- CIK cell ratio was 1: 20 in the coculture, CIK cells secreted the highest number of cytokines on the 14th day and the antitumor immune effect showed the highest potency. CIK cells' cytotoxicity to K562 cells was highest when the CIK: K562 cell ratio was 25: 1. We developed an efficient manufacturing process for DC- CIK coculture, while also establishing the optimal DC- CIK cell ratio for immunological activity and the best cytotoxic CIK: K562 cell ratio.

Therapeutic Applications of Mesenchymal Stem Cell Loaded with Gold Nanoparticles for Regenerative Medicine.

In the present study, the various concentrations of AuNP (1.25, 2.5, 5, 10 ppm) were prepared to investigate the biocompatibility, biological performances and cell uptake efficiency via Wharton's jelly mesenchymal stem cells and rat model. The pure AuNP, AuNP combined with Col (AuNP-Col) and FITC conjugated AuNP-Col (AuNP-Col-FITC) were characterized by Ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR) and Dynamic Light Scattering (DLS) assays. For in vitro examinations, we explored whether the Wharton's jelly MSCs had better viability, higher CXCR4 expression, greater migration distance and lower apoptotic-related proteins expression with AuNP 1.25 and 2.5 ppm treatments. Furthermore, we considered whether the treatments of 1.25 and 2.5 ppm AuNP could induce the CXCR4 knocked down Wharton's jelly MSCs to express CXCR4 and reduce the expression level of apoptotic proteins. We also treated the Wharton's jelly MSCs with AuNP-Col to investigate the intracellular uptake mechanisms. The evidence demonstrated the cells uptake AuNP-Col through clathrin-mediated endocytosis and the vacuolar-type H+-ATPase pathway with good stability inside the cells to avoid lysosomal degradation as well as better uptake efficiency. Additionally, the results from in vivo examinations elucidated the 2.5 ppm of AuNP attenuated foreign body responses and had better retention efficacy with tissue integrity in animal model. In conclusion, the evidence demonstrates that AuNP shows promise as a biosafe nanodrug delivery system for development of regenerative medicine coupled with Wharton's jelly MSCs.

Percutaneous endoscopic lumbar discectomy for L5-S1 disc herniation based on image analysis and clinical findings: A retrospective review of 345 cases.

The effect of spinal anatomical anomalies on the efficacy of percutaneous endoscopic lumbar discectomy (PELD) for disc herniation repair is unclear. This retrospective review aims to assess the safety and effectiveness of PELD for treating L5-S1 disc herniation with a range of characteristics and to determine the prevalence of lumbosacral transitional vertebrae (LSTV) anatomical anomalies to facilitate pre-surgical planning. From July 2005 to June 2019, 345 patients with L5-S1 disc herniations were treated with PELD. The primary outcome was 1-year postoperative visual analogue scale scores for low back and lower limb pain. The secondary outcomes included the surgical approach used, lumbosacral bony anomalies, presence of a ruptured disc or severely calcified disc, pediatric lumbar disc herniation, recurrent disc herniation management, and the long-term outcome. visual analogue scale scores for most patients were significantly improved after surgery. The prevalence of LSTVs was 4.05% (14/345 patients) in lumbar sacralization and 7.53% (26/345 patients) in sacral lumbarization. The prevalence of ruptured and severely calcified discs was 18.55% (64/345) and 5.79% (20/345), respectively. The prevalence of pediatric lumbar disc herniation was 2.02% (7/345). The recurrence rate was 4.34% (15/345). Two durotomy cases without sequelae and 8 cases of lower limb dysesthesia lasting longer than 3 months postoperatively were reported. PELD is safe and effective for treating L5-S1 disc herniation, including cases complicated by calcified lumbar disc herniation, disc rupture with migration, and the presence of LSTV. Appropriate imaging is essential to identify case-specific factors, including the prevalent LSTV anatomical anomalies, before surgery.

Bisdemethoxycurcumin suppresses human brain glioblastoma multiforme GBM 8401 cell migration and invasion via affecting NF-κB and MMP-2 and MMP-9 signaling pathway in vitro.

Human glioblastoma (GBM) is one of the common cancer death in adults worldwide, and its metastasis will lead to difficult treatment. Finding compounds for future to develop treatment is urgent. Bisdemethoxycurcumin (BDMC), a natural product, was isolated from the rhizome of turmeric (Curcuma longa), which has been shown to against many human cancer cells. In the present study, we evaluated the antimetastasis activity of BDMC in human GBM cells. Cell proliferation, cell viability, cellular uptake, wound healing, migration and invasion, and western blotting were analyzed. Results indicated that BDMC at 1.5-3 µM significantly decreased the cell proliferation by MTT assay. BDMC showed the highest uptake by cells at 3 h. After treatment of BDMC at 12-48 h significantly inhibited cell motility in GBM 8401 cells by wound healing assay. BDMC suppressed cell migration and invasion at 24 and 48 h treatment by transwell chamber assay. BDMC significantly decreased the levels of proteins associated with PI3K/Akt, Ras/MEK/ERK pathways and resulted in the decrease in the expressions of NF-κB, MMP-2, MMP-9, and N-cadherin, leading to the inhibition of cell migration and invasion. These findings suggest that BDMC may be a potential candidate for the antimetastasis of human GBM cells in the future.

Neural Differentiation Potential of Mesenchymal Stem Cells Enhanced by Biocompatible Chitosan-Gold Nanocomposites.

Chitosan (Chi) is a natural polymer that has been demonstrated to have potential as a promoter of neural regeneration. In this study, Chi was prepared with various amounts (25, 50, and 100 ppm) of gold (Au) nanoparticles for use in in vitro and in vivo assessments. Each as-prepared material was first characterized by UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), and Dynamic Light Scattering (DLS). Through the in vitro experiments, Chi combined with 50 ppm of Au nanoparticles demonstrated better biocompatibility. The platelet activation, monocyte conversion, and intracellular ROS generation was remarkably decreased by Chi-Au 50 pm treatment. Furthermore, Chi-Au 50 ppm could facilitate colony formation and strengthen matrix metalloproteinase (MMP) activation in mesenchymal stem cells (MSCs). The lower expression of CD44 in Chi-Au 50 ppm treatment demonstrated that the nanocomposites could enhance the MSCs undergoing differentiation. Chi-Au 50 ppm was discovered to significantly induce the expression of GFAP, ß-Tubulin, and nestin protein in MSCs for neural differentiation, which was verified by real-time PCR analysis and immunostaining assays. Additionally, a rat model involving subcutaneous implantation was used to evaluate the superior anti-inflammatory and endothelialization abilities of a Chi-Au 50 ppm treatment. Capsule formation and collagen deposition were decreased. The CD86 expression (M1 macrophage polarization) and leukocyte filtration (CD45) were remarkably reduced as well. In summary, a Chi polymer combined with 50 ppm of Au nanoparticles was proven to enhance the neural differentiation of MSCs and showed potential as a biosafe nanomaterial for neural tissue engineering.

Severe heterotopic ossification in a seronegative spondyloarthritis patient after cervical Bryan disc arthroplasty: A case report.

BACKGROUND: Cervical disc arthroplasty (CDA) is an alternative treatment to traditional interbody fusion that maintains postoperative cervical spine mobility. However, the CDA postoperative period is impacted by osteolysis, subsidence, metallosis, or heterotopic ossification (HO). We report a case of severe HO in a seronegative spondyloarthritis patient after cervical Bryan disc arthroplasty. CASE SUMMARY: A 34-year-old man received hybrid surgery for C4-C5 and C5-C6 arthroplasty with Bryan discs and C6-C7 arthrodesis with polyetheretherketone cage due to traumatic herniation of the intervertebral disc (HIVD). After four years, cervical spine radiographs revealed severe HO around the Bryan discs over the C4-C5 and C5-C6 levels. The magnetic resonance image revealed HIVD over the C3-C4 level with spinal cord compression. Seronegative spondyloarthritis was diagnosed after consultation with a rheumatologist. A second CDA for the adjacent segment disease HIVD with Baguera C disc over the C3-C4 level achieved an excellent outcome. CONCLUSION: Minimizing intraoperative tissue trauma and achieving postoperative interbody stability avoid soft tissue traction to prevent HO formation after CDA.

Metallosis after traumatic loosening of Bryan cervical disc arthroplasty: a case report and literature review.

PURPOSE: Cervical disc arthroplasty has been a popular alternative to traditional arthrodesis treatment for maintaining postoperative cervical spine mobility. However, certain adverse reactions to cervical disc arthroplasty have emerged during the last few decades. METHODS: Metallosis or metalloma is a rarely reported complication after spinal fusion or spinal arthroplasty surgery. We report on the first metallosis case occurring in a patient who received Bryan Disc implantation approximately 8 years earlier. She was involved in a traffic accident and sustained a whiplash injury to the cervical spine one and a half years ago. The traumatic Bryan Disc loosening developed after the traffic accident, causing metallosis. RESULTS: To the best of our knowledge, this is the first reported case of spinal metallosis caused by the Bryan Disc. A series of metallosis cases reported in the literature are also reviewed. CONCLUSIONS: Although uncommon, intraspinal metallosis or metalloma should be considered as an infrequent cause of delayed neurological symptoms after spinal surgery involving metallic instrumentation, especially after disc arthroplasty. Once metallosis is suspected, immediate metallic implant removal is mandatory for definite diagnosis and treatment.

Endoscope-assisted transsphenoidal puncture of the cavernous sinus for embolization of carotid-cavernous fistula in a neurosurgical hybrid operating suite.

Endovascular embolization is the treatment of choice for carotid-cavernous fistulas (CCFs), but failure to catheterize the cavernous sinus may occur as a result of vessel tortuosity, hypoplasia, or stenosis. In addition to conventional transvenous or transarterial routes, alternative approaches should be considered. The authors present a case in which a straightforward route to the CCF was accessed via transsphenoidal puncture of the cavernous sinus in a neurosurgical hybrid operating suite. This 82-year-old man presented with severe chemosis and proptosis of the right eye. Digital subtraction angiography revealed a Type B CCF with a feeding artery arising from the meningohypophyseal trunk of the right cavernous segment of the internal carotid artery. The CCF drained through a thrombosed right superior ophthalmic vein that ended deep in the orbit; there were no patent sinuses or venous plexuses connecting to the CCF. An endoscope-assisted transsphenoidal puncture created direct access to the nidus for embolization. Embolic agents were deployed through the puncture needle to achieve complete obliteration. Endoscope-assisted transsphenoidal puncture of the cavernous sinus is a feasible alternative to treat difficult-to-access CCFs in a neurosurgical hybrid operating suite.

Total sleep deprivation augments balloon angioplasty-induced neointimal hyperplasia in rats.

Sleep deprivation has been shown to be associated with an increase in inflammation that is also involved in the development of neointimal hyperplasia (or restenosis). The purpose of this study was to investigate whether total sleep deprivation (TSD) would worsen neointimal formation by balloon injury. Sixteen rats were randomly allocated into the following four groups: group 1, balloon angioplasty alone; group 2, TSD prior to angioplasty; group 3, angioplasty before TSD; and group 4, TSD before and after angioplasty. Total sleep deprivation was induced by the disc-over-water method, and balloon angioplasty was performed in the carotid artery. Histopathological analysis and assay of cytokines were applied to evaluate the effects of TSD in this study. Total sleep deprivation significantly increased the ratio of postinjury neointima-to-media area in groups 2, 3 and 4 (all P < 0.01) compared with group 1. Additionally, in all groups with TSD administration the serum level of interleukin 10 was also markedly decreased on day 3 after angioplasty injury (P < 0.05 or P < 0.01). Our findings suggest that perioperative TSD can significantly augment neointimal hyperplasia of the carotid artery in rats, which may be partly caused by a TSD-induced effect in suppressing the serum level of the anti-inflammatory cytokine, interleukin 10.