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Oxygen-laden mesenchymal stem cells enhance the effect of gastric cancer chemotherapy in vitro.

ABSTRACT: Hypoxia is an important factor that results in failure of chemotherapy for the majority of solid tumor types, particularly for gastric cancer. In the present study, mesenchymal stem cells (MSCs), which have the ability to migrate to cancer tissues were used as a vehicle to supply oxygen to gastric cancer. The hemoglobin genes were transfected into MSCs as MSC-hemo groups. Subsequently, MSC-hemo groups were induced by isopropyl-b-D-thiogalactopyranoside and hemin to express hemoglobin. The hemoglobin was detected by western blotting method. Following this, the MSC-hemo groups were placed in an atmosphere containing 100% oxygen and were used to investigate the effect of the function of the oxygen-laden MSC-hemo group on gastric cancer chemotherapy with an MTT assay. As a first approach to investigate the possibility of MSCs as a vehicle to supply oxygen to anoxic cancer types, including gastric, liver, breast cancer, the results indicated that the oxygen-laden MSC-hemo group significantly enhanced the effect of chemotherapeutic treatments on gastric cancer cells. Utilizing MSCs as a svehicle to supply oxygen to the solid tumor may be a novel method to improve the hypoxia conditions of tumor tissues and improve the effect of chemotherapy on tumor cells.

SUBMITTER: Zhou YL

PROVIDER: S-EPMC6312988 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Oxygen-laden mesenchymal stem cells enhance the effect of gastric cancer chemotherapy <i>in vitro</i>.

Zhou Ya-Li YL Li Yu-Min YM He Wen-Ting WT

Oncology letters 20181107 1

Hypoxia is an important factor that results in failure of chemotherapy for the majority of solid tumor types, particularly for gastric cancer. In the present study, mesenchymal stem cells (MSCs), which have the ability to migrate to cancer tissues were used as a vehicle to supply oxygen to gastric cancer. The hemoglobin genes were transfected into MSCs as MSC-hemo groups. Subsequently, MSC-hemo groups were induced by isopropyl-b-D-thiogalactopyranoside and hemin to express hemoglobin. The hemogl ...[more]

PMID: 30655891

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Project description:BackgroundFollowing an ischemic injury to the brain, the induction of angiogenesis is critical to neurological recovery. The angiogenic benefits of mesenchymal stem cells (MSCs) have been attributed at least in part to the actions of extracellular vesicles (EVs) that they secrete. EVs are membrane-bound vesicles that contain various angiogenic biomolecules capable of eliciting therapeutic responses and are of relevance in cerebral applications due to their ability to cross the blood-brain barrier (BBB). Though MSCs are commonly cultured under oxygen levels present in injected air, when MSCs are cultured under physiologically relevant oxygen conditions (2-9% O2), they have been found to secrete higher amounts of survival and angiogenic factors. There is a need to determine the effects of MSC-EVs in models of cerebral angiogenesis and whether those from MSCs cultured under physiological oxygen provide greater functional effects.MethodsHuman adipose-derived MSCs were grown in clinically relevant serum-free medium and exposed to either headspace oxygen concentrations of 18.4% O2 (normoxic) or 3% O2 (physioxic). EVs were isolated from MSC cultures by differential ultracentrifugation and characterized by their size, concentration of EV specific markers, and their angiogenic protein content. Their functional angiogenic effects were evaluated in vitro by their induction of cerebral microvascular endothelial cell (CMEC) proliferation, tube formation, and angiogenic and tight junction gene expressions.ResultsCompared to normoxic conditions, culturing MSCs under physioxic conditions increased their expression of angiogenic genes SDF1 and VEGF, and subsequently elevated VEGF-A content in the EV fraction. MSC-EVs demonstrated an ability to induce CMEC angiogenesis by promoting tube formation, with the EV fraction from physioxic cultures having the greatest effect. The physioxic EV fraction further upregulated the expression of CMEC angiogenic genes FGF2, HIF1, VEGF and TGFB1, as well as genes (OCLN and TJP1) involved in BBB maintenance.ConclusionsEVs from physioxic MSC cultures hold promise in the generation of a cell-free therapy to induce angiogenesis. Their positive angiogenic effect on cerebral microvascular endothelial cells demonstrates that they may have utility in treating ischemic cerebral conditions, where the induction of angiogenesis is critical to improving recovery and neurological function.

Project description:Bone regeneration poses a significant challenge in the field of tissue engineering, prompting ongoing research to explore innovative strategies for effective bone healing. The integration of stem cells and nanomaterial scaffolds has emerged as a promising approach, offering the potential to enhance regenerative outcomes. This study focuses on the application of a stem cell-laden nanomaterial scaffold designed for bone regeneration in rabbits. The in vivo study was conducted on thirty-six healthy skeletally mature New Zealand white rabbits that were randomly allocated into six groups. Group A was considered the control, wherein a 15 mm critical-sized defect was created and left as such without any treatment. In group B, this defect was filled with a polycaprolactone-hydroxyapatite (PCL + HAP) scaffold, whereas in group C, a PCL + HAP-carboxylated multiwalled carbon nanotube (PCL + HAP + MWCNT-COOH) scaffold was used. In group D, a PCL + HAP + MWCNT-COOH scaffold was used with local injection of bone morphogenetic protein-2 (BMP-2) on postoperative days 30, 45, and 60. The rabbit bone marrow-derived mesenchymal stem cells (rBMSCs) were seeded onto the PCL + HAP + MWCNT-COOH scaffold by the centrifugal method. In group E, an rBMSC-seeded PCL + HAP + MWCNT-COOH scaffold was used along with the local injection of rBMSC on postoperative days 7, 14, and 21. For group F, in addition to the treatment given to group E, BMP-2 was administered locally on postoperative days 30, 45, and 60. Gross observations, radiological observation, scanning electron microscopic assessment, and histological evaluation study showed that group F displayed the best healing properties, followed by group E, group D, group C, and B. Group A showed no healing with ends blunting minimal fibrous tissue. Incorporating growth factor BMP-2 in tissue-engineered rBMSC-loaded nanocomposite PCL + HAP + MWCNT-COOH construct can augment the osteoinductive and osteoconductive properties, thereby enhancing the healing in a critical-sized bone defect. This novel stem cell composite could prove worthy in the treatment of non-union and delayed union fractures in the near future.

Dataset Information

Oxygen-laden mesenchymal stem cells enhance the effect of gastric cancer chemotherapy in vitro.

Publications

Oxygen-laden mesenchymal stem cells enhance the effect of gastric cancer chemotherapy <i>in vitro</i>.

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