Intratumoral hypoxia, which is in favour of cancer cell proliferation, invasion and metastasis, also inhibits photodynamic therapy (PDT) badly. Herein, second near-infrared (NIR-II) photocatalytic O₂ production is established to realize hypoxia relief. MoS₂/Co₃S₄@PEG (MSCs@PEG) nanoflowers (100-150 nm) are prepared via a two-step hydrothermal method. These samples possess high NIR-II harvest and photothermal conversion (39.8 %, 1064 nm) ability. That not only reveals photothermal therapy (PTT) but also lifts the thermal energy of nanomaterials to replenish extra energy, making sure the co-excitation of MoS₂ (1.14 eV) and Co₃S₄ (1.40 eV) by low-energy NIR-II (1064 nm, 1.16 eV) laser. The investigation of band structure further displays the Z-Scheme characterization of MSCs heterostructure. These photo-excited holes/electrons hold great redox ability to form O₂ (water splitting) and reactive oxygen species (ROS), simultaneously. In addition, MSC-2@PEG can be served to mimic catalase, peroxidase, and glutathione (GSH) oxidase to further boost oxidative stress. It is noted that heterostructure discovers the greater nanozyme activity, attributing to the lower resistance for charge transfer. Moreover, MSC-2@PEG displays a novel biodegradation ability to induce the elimination via urine and faeces within 14 days. Given the superparamagnetic and photothermal effect, the nanocomposite can be used as magnetic resonance and photothermal imaging (MRI and PTI) contrast. Associated with dual-imaging, intracellular O₂ supplementation, and synergistic chemotherapy (CDT)/PTT/PDT, MSC-2@PEG possess great tumor inhibition that also efficiently motivates immune response for anticancer.

01 Dec 2021·Regenerative TherapyQ3 · ENGINEERING & TECHNOLOGY

Immunosuppressive mesenchymal stem cells aggregates incorporating hydrogel microspheres promote an in vitro invasion of cancer cells

Q3 · ENGINEERING & TECHNOLOGY

ArticleOA

Author: Nii, Teruki ; Tabata, Yasuhiko

INTRODUCTIONThe objective of this study is to design a co-culture system of cancer cells and three-dimensional (3D) mesenchymal stem cells (MSC) aggregates for the in vitro evaluation of cancer invasion.METHODSFirst, the MSC of an immunosuppressive phenotype (MSC2) were prepared by the MSC stimulation of polyriboinosinic polyribocytidylic acid. By simple mixing MSC2 and gelatin hydrogel microspheres (GM) in a U-bottomed well of 96 well plates which had been pre-coated with poly (vinyl alcohol), 3D MSC2 aggregates incorporating GM were obtained. The amount of chemokine (C-C motif) ligand 5 (CCL5) secreted from the MSC2 aggregates incorporating GM. Finally, an invasion assay was performed to evaluate the cancer invasion rate by co-cultured cancer cells and the 3D MSC2 incorporating GM.RESULTSThe amount of CCL5 secreted for the 3D MSC2 aggregates incorporating GM was significantly higher than that of two-dimensional (2D) MSC, 2D MSC2, and 3D MSC aggregates incorporating GM. When MDA-MB-231 human breast cancer cells were co-cultured with the 3D MSC2 aggregates incorporating GM, the invasion rate of cancer cells was significantly high compared with that of 2D MSC or 2D MSC2 and 3D MSC aggregates incorporating GM. In addition, high secretion of matrix metalloproteinase-2 was observed for the 3D MSC2 aggregates/cancer cells system.CONCLUSIONSIt is concluded that the co-culture system of 3D MSC2 aggregates incorporating GM and cancer cells is promising to evaluate the invasion of cancer cells in vitro.

01 Mar 2019·Stem Cells Translational Medicine

Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial

Article

Author: Alcayaga-Miranda, Francisca ; Tapia-Limonchi, Rafael ; Cadiz, Maria Ignacia ; Matas, Jose ; Amenabar, Diego ; Muse, Emilio ; Figueroa, Fernando E. ; González, Paz L. ; Orrego, Mario ; Khoury, Maroun ; Espinoza, Francisco ; Infante, Catalina

AbstractKnee osteoarthritis (OA) is a leading cause of pain and disability. Although conventional treatments show modest benefits, pilot and phase I/II trials with bone marrow (BM) and adipose-derived (AD) mesenchymal stromal cells (MSCs) point to the feasibility, safety, and occurrence of clinical and structural improvement in focal or diffuse disease. This study aimed to assess the safety and efficacy of the intra-articular injection of single or repeated umbilical cord-derived (UC) MSCs in knee OA. UC-MSCs were cultured in an International Organization for Standardization 9001:2015 certified Good Manufacturing Practice-type Laboratory. Patients with symptomatic knee OA were randomized to receive hyaluronic acid at baseline and 6 months (HA, n = 8), single-dose (20 × 106) UC-MSC at baseline (MSC-1, n = 9), or repeated UC-MSC doses at baseline and 6 months (20 × 106 × 2; MSC-2, n = 9). Clinical scores and magnetic resonance images (MRIs) were assessed throughout the 12 months follow-up. No severe adverse events were reported. Only MSC-treated patients experienced significant pain and function improvements from baseline (p = .001). At 12 months, Western Ontario and Mc Master Universities Arthritis Index (WOMAC-A; pain subscale) reached significantly lower levels of pain in the MSC-2-treated group (1.1 ± 1.3) as compared with the HA group (4.3 ± 3.5; p = .04). Pain Visual Analog scale was significantly lower in the MSC-2 group versus the HA group (2.4 ± 2.1 vs. 22.1 ± 9.8, p = .03) at 12 months. For total WOMAC, MSC-2 had lower scores than HA at 12 months (4.2 ± 3.9 vs. 15.2 ± 11, p = .05). No differences in MRI scores were detected. In a phase I/II trial (NCT02580695), repeated UC-MSC treatment is safe and superior to active comparator in knee OA at 1-year follow-up. Stem Cells Translational Medicine 2019;8:215&224

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