mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation

Levy, Oren; Zhao, Weian; Mortensen, Luke J.; LeBlanc, Sarah; Tsang, Kyle; Fu, Moyu; Phillips, Joseph A.; Sagar, Vinay; Anandakumaran, Priya N.; Ngai, Jessica; Cui, Cheryl H.; Eimon, Peter M.; Angel, Matthew; Lin, Charles P.; Yanik, Mehmet Fatih; Karp, Jeffrey M.

doi:10.1182/blood-2013-04-495119

Cited by 176 publications

(179 citation statements)

References 50 publications

(77 reference statements)

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“…We propose that detection of enhanced IL-10 (probably via FoxP3 signaling pathway) during relative conditions may represent the development of an immunity Bswitch^and, therefore, a predictor of this process [72]. Under resting conditions or at the initial time of response, the relatively low IL-10 production originates mainly from the cells of central immune system [159][160][161]. During the successive period, there is transient IL-10 induction, directly from the Bintact^immune system or under the manipulative effect of infective agents and tumor tissue [72,89,116,120,132,157,161].…”

Section: Il-10-an Indicator and Time-dependent Effector Of Immunity Smentioning

confidence: 99%

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Mingomataj

Bakiri

2015

Clinic Rev Allerg Immunol

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The interleukin-10 (IL-10) is generally considered as the most important cytokine with anti-inflammatory properties and one of the key cytokines preventing inflammation-mediated tissue damage. In this respect, IL-10 producing cells play a crucial role in the outcome of infections, allergy, autoimmune reactions, tumor development, and transplant tolerance. Based on recent findings with regard to the mentioned clinical conditions, this review attempts to shed some light on the IL-10 functions, considering this cytokine as inherent inducer of the switching immunity. While acute infections and vaccinations are associated by IL-10 enhanced during few weeks, chronic parasitoses, tumor diseases, allergen-specific immunotherapy, transplants, and use of immune-suppressor drugs show an increased IL-10 level along months or years. With regard to autoimmune pathologies, the IL-10 increase is prevalently observed during early stages, whereas the successive stages are characterized by reaching of immune equilibrium independently to disease's activity. Together, these findings indicate that IL-10 is mainly produced during transient immune conditions and the persistent IL-10-related effect is the indication/prediction (and maybe effectuation) of the switching immunity. Actual knowledge emphasizes that any manipulation of the IL-10 response for treatment purposes should be considered very cautiously due to its potential hazards to the immune system. Probably, the IL-10 as potential switcher of immunity response should be used in association with co-stimulatory immune effectors that are necessary to determine the appropriate deviation during treatment of respective pathologies. Hopefully, further findings would open new avenues to study the biology of this "master switch" cytokine and its therapeutic potential.

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Section: Il-10-an Indicator and Time-dependent Effector Of Immunity Smentioning

confidence: 99%

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Mingomataj

Bakiri

2015

Clinic Rev Allerg Immunol

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“…Cell-cell and cell-extracellular matrices interactions through these molecules play important roles in embryo development and tissue morphogenesis, and also in cell and tissue functions in adults. Previous investigations have modified the cell surface in an effort to control these interactions with biomolecules and to examine their potential in biomedical applications, such as nucleic acid or protein delivery to cells [1,2], cell delivery to a particular organ [3], and tissue engineering to promote the regeneration of tissues [4]. The methods to modify the cell surface can be grouped into three categories: covalent conjugation; electrostatic interaction; and hydrophobic interaction between amphiphilic molecules with the lipid bilayer of the cell membrane [5,6].…”

Section: Introductionmentioning

confidence: 99%

Interaction between cells and poly(ethylene glycol)-lipid conjugates

Itagaki

Arima

Kuwabara

et al. 2015

Colloids and Surfaces B: Biointerfaces

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Eight types of poly(ethylene glycol)-lipid(PEG-lipids) carrying different lipid tails were synthesized. These PEG-lipids were labeled with fluorescein isothiocyanate (FITC-PEG-lipids) to examine their interaction with cells and to quantitatively determine amounts of PEG-lipids bound on the cell surface. FITC-PEG-lipids spontaneously anchored to the cell membrane within 15 min without loss of cell viability. The type of lipid had very little effect on the anchoring rates, while an increase in the hydrophobicity of the lipid portion of the PEG-lipids slowed their dissociation rates. Densities of FITC-PEG-lipids on the cell surface ranged from 1 × 10(-3) to 1 × 10(-2)molecules/nm(2), depending on the kinds of lipids employed. The relationship between the stability of the lipids on the cell membrane and the hydrophobicity of the lipid moieties will give a basis for the selection of a hydrophobic moiety in PEG-lipid conjugates for use in specific applications.

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“…By using stem cells as drug delivery vehicles, different biological drugs have been delivered, including chemotherapeutic agents, prodrugs (10)(11)(12)(13), and genetic signals (14). One limitation of delivering chemotherapeutic agents is that they generally could not differentiate cancerous cells from normal cells.…”

mentioning

confidence: 99%

Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery

Jiang

Fitch

Wang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Glioblastoma multiforme (GBM) is one of the most intractable of human cancers, principally because of the highly infiltrative nature of these neoplasms. Tracking and eradicating infiltrating GBM cells and tumor microsatellites is of utmost importance for the treatment of this devastating disease, yet effective strategies remain elusive. Here we report polymeric nanoparticle-engineered human adipose-derived stem cells (hADSCs) overexpressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as drug-delivery vehicles for targeting and eradicating GBM cells in vivo. Our results showed that polymeric nanoparticle-mediated transfection led to robust up-regulation of TRAIL in hADSCs, and that TRAIL-expressing hADSCs induced tumor-specific apoptosis. When transplanted in a mouse intracranial xenograft model of patient-derived glioblastoma cells, hADSCs exhibited long-range directional migration and infiltration toward GBM tumor. Importantly, TRAIL-overexpressing hADSCs inhibited GBM growth, extended survival, and reduced the occurrence of microsatellites. Repetitive injection of TRAIL-overexpressing hADSCs significantly prolonged animal survival compared with single injection of these cells. Taken together, our data suggest that nanoparticle-engineered TRAIL-expressing hADSCs exhibit the therapeutically relevant behavior of "seek-and-destroy" tumortropic migration and could be a promising therapeutic approach to improve the treatment outcomes of patients with malignant brain tumors.nanoparticle | adipose-derived stem cells | TRAIL | glioblastoma | tumor microsatellites

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mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation

Abstract: Key Points mRNA transfection is an effective tool to simultaneously engineer MSCs for enhanced homing and improved secretome. MSCs can be systemically targeted to sites of inflammation to achieve therapeutically relevant concentrations of biological agents.

Cited by 176 publications

References 50 publications

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Interaction between cells and poly(ethylene glycol)-lipid conjugates

Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery

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