Mesenchymal stem cells expressing anti-inflammatory cytokines and methods of use
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsTzuhua Lin, Jukka Pajarinen, Stuart B. Goodman
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AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsTzuhua Lin, Jukka Pajarinen, Stuart B. Goodman
Estimating the term…
Provided are compositions and methods for production of anti-inflammatory cytokines, growth factors, or chemokines. Provided are nucleic acids (e.g., expression vectors) that include an NFκB inflammation response element operably linked to a nucleotide sequence encoding an anti-inflammatory cytokine (e.g., IL-4). In some cases, the nucleic acid is an expression vector selected from: a linear expression vector, a circular expression vector, a plasmid, and a viral expression vector. Also provided are cells (e.g., mesenchymal stem cells—MSCs) comprising a nucleic acid that includes an NFκB inflammation response element operably linked to a nucleotide sequence encoding an anti-inflammatory cytokine. In some cases, the nucleic acid is integrated into the cell's genome. Also provided are methods for treating an individual having an inflammation-associated ailment, which can include administering an MSC to the individual, where the MSC includes an NFκB inflammation response element operably linked to a nucleotide sequence encoding an anti-inflammatory cytokine.
A population of isolated mammalian mesenchymal stem cells (MSCs) each of which comprises a heterologous nucleic acid sequence comprising a nucleotide sequence encoding an anti-inflammatory cytokine operably linked to a nuclear factor kappa B (NFκB) inflammation responsive element, wherein the population is capable expressing the anti-inflammatory cytokine in an amount sufficient to modulate inflammatory M1 macrophages into an anti-inflammatory M2 macrophage phenotype, and further wherein the anti-inflammatory cytokine is interleukin 4 (IL-4).
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