Induction medium and methods for stem cell culture and therapy

Inventors

BETANCOURT, Aline

Assignees

Sanbio Inc

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Publication Number

US-11046929-B2

Patent

Publication Date

2021-06-29

Expiration Date


Abstract

Novel MSC stem-cell culture and therapy methods and culture medium compositions for the purpose of inducing, activating, or priming discrete uniform cell phenotypes to selectively promote or suppress inflammation and immunity, yielding polarized, primed, activated, or induced cells used in cell-based therapy.

Core Innovation

The invention provides an induced mesenchymal stem cell population with an anti-inflammatory phenotype. The induced population is obtained by treating mesenchymal stem cells with an induction medium comprising a Toll-like receptor 3 (TLR3) ligand, erythropoietin, and a hypoxia mimetic. The core concept links Toll-like receptor 3 activation and erythropoietin with hypoxia signaling to generate an anti-inflammatory MSC phenotype.

A further aspect defines inducing the anti-inflammatory phenotype under hypoxic conditions of 0.5% to 2% oxygen using an induction medium comprising a Toll-like receptor 3 (TLR3) ligand and erythropoietin. The document states that TLR3-related polarization supports production of an anti-inflammatory phenotype, with hypoxia maintained as part of the induction conditions. In this framework, the TLR3 ligand and erythropoietin act together under hypoxia to shape the resulting induced MSC population.

The document also describes variants of the induction medium, including TLR3 ligand options such as poly(I:C) and poly(A:U), and the ability to add interleukin 4 (IL-4) and/or interleukin 13 (IL-13). Additional formulation constraints are described, including an induction medium that does not comprise serum of human or animal origin. The induced cells can be treated as isolated from the induction medium and characterized by anti-inflammatory or immunosuppressive mediators.

Claims Coverage

The partial content contains two independent claims. Across these claims, the main inventive coverage centers on inducing an anti-inflammatory mesenchymal stem cell population using TLR3 signaling with erythropoietin together with hypoxia, either via a hypoxia mimetic or via defined hypoxic oxygen conditions (0.5% to 2%).

Induction medium with TLR3 ligand, erythropoietin, and hypoxia mimetic

An induced mesenchymal stem cell population with an anti-inflammatory phenotype obtained by treating mesenchymal stem cells with an induction medium comprising: a Toll-like receptor 3 (TLR3) ligand; erythropoietin; and a hypoxia mimetic.

Hypoxic conditions with TLR3 ligand and erythropoietin

An induced mesenchymal stem cell population with an anti-inflammatory phenotype obtained by treating mesenchymal stem cells under hypoxic conditions of 0.5% to 2% oxygen with an induction medium comprising: a Toll-like receptor 3 (TLR3) ligand; and erythropoietin.

The claims are directed to creating an anti-inflammatory MSC population through a TLR3-erythropoietin/hypoxia induction scheme, with hypoxia implemented either through a hypoxia mimetic or through hypoxic oxygen conditions of 0.5% to 2% oxygen.

Stated Advantages

Documented Applications

No documented applications found

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