Thymic cell compositions and methods of making
AssigneeThymmune Therapeutics, Inc.
InventorsBing Lim, Stan Wang, Behzad Gerami-Naini, Qiumei Du, Henry Thomas Beaman, Jr., Benjamin A. Schwarz
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Abstract
The present disclosure provides thymic cells, thymic organoids, and animal models comprising such thymic cells and thymic organoids. It also provides methods for inducing differentiation of pluripotent stem cells into definitive endoderm (DE), anterior foregut endoderm (AFE), ventral pharyngeal endoderm (VPE), thymic epithelial progenitor (TEP) cells, thymic epithelial cells (TECs) and thymic organoids in vitro and in vivo.
Claims39
A method of differentiating pluripotent stem cells to thymic cells, comprising:
- a) differentiating the pluripotent stem cells into definitive endoderm (DE) cells;
- c) culturing the DE cells and differentiating the DE cells into anterior foregut endoderm (AFE) cells by contacting or incubating the DE cells with a BMP inhibitor, a TGFβ inhibitor, an FGF, an ascorbic acid or a combination thereof;
- d) culturing the AFE cells and differentiating the anterior foregut cells into ventral pharyngeal endoderm (VPE) cells comprising:
- i) contacting or incubating the AFE cells in a first VPE medium comprising ascorbic acid, a retinoic acid, an FGF, a TGFβ inhibitor or a combination thereof, and
- ii) contacting or incubating the AFE cells in a second VPE medium comprising a Noggin, a WNT activator, an FGF, a retinoic acid, an ascorbic acid, or a combination thereof, and
- e) culturing the VPE cells and differentiating the VPE cells into thymic cells, by contacting or incubating the VPE cells with an ascorbic acid, an FGF, a BMP, a WNT activator or a combination thereof;
- wherein the thymic cells are thymic epithelial progenitor cells (TEPs) and/or thymic epithelial cells (TECs).
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A composition comprising:
- a) a population of thymic cells, wherein the population of thymic cells comprises one or more of an iTEC, mTECs, Corneocyte-like mTEC, cTEC-high, cTEC-low, mTEC-low cell;
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- b) a thymic support system (TSS).
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The composition of claim 30, wherein the level of FOXN1 production in vitro by a sample of the thymic cell population having a concentration of about 200,000 thymic cells per milliliter is greater than 0.0001 when measured by qRT-PCR and normalized against GADPH.
A method of treating or preventing a condition in a subject comprising administering to the subject the composition of as in claim 30.
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A method of improving acceptance of an organ transplant and/or preventing rejection of an organ transplant in a subject receiving an organ transplant comprising administering to the subject the composition as in of claim 30.
Dependencies are inferred from the claim text.