Improved methods of preparing different mesoderm cell types
AssigneesChildren's Hospital Medical Center, Riken
InventorsAaron M. ZORN, Lu HAN, Keishi KISHIMOTO, Mitsuru MORIMOTO
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Abstract
Disclosed herein are improved in vitro methods of making splanchnic mesoderm cell types and subtypes thereof from pluripotent cells. These methods can be used to produced improved foregut- and hindgut-derived organoids containing enriched mesenchyme, which enhances organoid viability, growth, and maturation, both in in vitro culture and in vivo transplantation.
Claims27
A method of producing retinoic acid-responsive lateral plate mesoderm cells (RA-LPM), comprising:
- inhibiting a TGF-beta signaling pathway, inhibiting a Wnt signaling pathway, activating a BMP signaling pathway, and activating a retinoic acid (RA) signaling pathway in middle primitive streak cells, thereby differentiating the middle primitive streak cells to RA-LPM.
A method of producing retinoic acid-responsive splanchnic mesoderm cells (RA-SpM), comprising:
- inhibiting a TGF-beta signaling pathway, inhibiting a Wnt signaling pathway, activating a BMP signaling pathway, activating an FGF signaling pathway, and activating a RA signaling pathway in RA-LPM, thereby differentiating the RA-LPM to RA-SpM.
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A population of cells comprising retinoic acid-responsive lateral plate mesoderm cells (RA-LPM), retinoic acid-responsive splanchnic mesoderm cells (RA-SpM), septum transversum (STM) and mesothelium cells, liver fibroblasts (LF), gastric mesenchyme cells (GM), hedgehog-responsive lateral plate mesoderm cells (HH-LPM), hedgehog-responsive splanchnic mesoderm cells (HH-SpM), esophageal mesenchyme cells (EM), respiratory mesenchyme cells (RM), or any combination thereof.
Dependencies are inferred from the claim text.