MilliporeSigma
  • Home
  • Search Results
  • IL-21-Expressing Mesenchymal Stem Cells Prevent Lethal B-Cell Lymphoma Through Efficient Delivery of IL-21, Which Redirects the Immune System to Target the Tumor.

IL-21-Expressing Mesenchymal Stem Cells Prevent Lethal B-Cell Lymphoma Through Efficient Delivery of IL-21, Which Redirects the Immune System to Target the Tumor.

Stem cells and development (2015-09-29)
Nayoun Kim, Young-Sun Nam, Keon-Il Im, Jung-Yeon Lim, Eun-Sol Lee, Young-Woo Jeon, Seok-Goo Cho
ABSTRACT

Interleukin (IL)-21, a proinflammatory cytokine, has been developed as an immunotherapeutic approach due to its effects on various lymphocytes, including natural killer (NK) cells and T cells; however, the clinical success in cancer patients has been limited. Recently, mesenchymal stem cells (MSCs) have emerged as vehicles for cancer gene therapy due to their inherent migratory abilities toward tumors. In the present study, we hypothesized that MSCs, genetically modified to express high levels of IL-21 (IL-21/MSCs), can enhance antitumor responses through localized delivery of IL-21. For tumor induction, BALB/c mice were injected intravenously with syngeneic A20 B-cell lymphoma cells to develop a disseminated B-cell lymphoma model. Then, 6 days following tumor induction, the tumor-bearing mice were treated with IL-21/MSCs weekly, four times. Systemic infusion of A20 cells led to hind-leg paralysis as well as severe liver metastasis in the control group. The IL-21/MSC-treated group showed delayed tumor incidence as well as improved survival, whereas the MSC- and recombinant adenovirus-expressing IL-21 (rAD/IL-21)-treated groups did not show significant differences from the untreated mice. These therapeutic effects were associated with high levels of IL-21 delivered to the liver, which prevented the formation of tumor nodules. Furthermore, the infusion of IL-21/MSCs led to induction of effector T and NK cells, while potently inhibiting immune suppressor cells. Our findings demonstrate that IL-21-expressing MSCs have the therapeutic potential to induce potent antitumor effects against disseminated B-cell lymphoma through localized IL-21 delivery and induction of systemic antitumor immunity.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
IL-21 human, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Sigma-Aldrich
IL-21 human, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
SAFC
L-Glutamine
Supelco
Hematoxylin
Sigma-Aldrich
Hematoxylin, certified by the Biological Stain Commission
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Propidium iodide solution, solution (1.0 mg/ml in water)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
SAFC
Formaldehyde solution, contains 10-15% methanol as stabilizer, 37 wt. % in H2O
Sigma-Aldrich
Sodium chloride solution, 0.9% in water, BioXtra, suitable for cell culture
Sigma-Aldrich
Diethanolamine, ACS reagent, ≥98.5%
Sigma-Aldrich
Sodium chloride, 99.999% trace metals basis
Sigma-Aldrich
Sodium chloride solution, 5 M in H2O, BioReagent, for molecular biology, suitable for cell culture
Sigma-Aldrich
Sodium chloride solution, 5 M
Sigma-Aldrich
Propidium iodide, ≥94.0% (HPLC)
Supelco
Formaldehyde solution, stabilized with methanol, ~37 wt. % in H2O, certified reference material
Sigma-Aldrich
Aphidicolin from Nigrospora sphaerica, ≥98% (HPLC), powder
Sigma-Aldrich
Sodium chloride, tablet
Sigma-Aldrich
Sodium chloride, for molecular biology, DNase, RNase, and protease, none detected, ≥99% (titration)
Sigma-Aldrich
Sodium chloride, BioXtra, ≥99.5% (AT)
Sigma-Aldrich
Sodium chloride, BioUltra, for molecular biology, ≥99.5% (AT)