STRATEGY FOR ENGINEERING VARIOUS 3D TISSUES, ORGANOIDS AND VASCULATURE

• US 20150284689A1
• Filed: 10/24/2013
• Published: 10/08/2015
• Est. Priority Date: 10/26/2012
• Status: Abandoned Application

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Nigam, Sanjay K.
• Application Number:
  US14/438,334
• Publication Number:
  US 20150284689A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3625 Vascular tissue, e.g. heart valves
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: C12N 2501/00 Active agents used in cell culture processes, e.g. differentation
• CPC Class Codes: C12N 2501/10 Growth factors
• CPC Class Codes: C12N 2501/113 Acidic fibroblast growth factor (aFGF, FGF-1)
• CPC Class Codes: C12N 2501/117 Keratinocyte growth factors (KGF-1, i.e. FGF-7; KGF-2, i.e. FGF-12)
• CPC Class Codes: C12N 2501/12 Hepatocyte growth factor [HGF]
• CPC Class Codes: C12N 2501/13 Nerve growth factor [NGF]; Brain-derived neurotrophic factor [BDNF]; Cilliary neurotrophic factor [CNTF]; Glial-derived neurotrophic factor [GDNF]; Neurotrophins [NT]; Neuregulins
• CPC Class Codes: C12N 2501/148 Transforming growth factor alpha [TGF-a]
• CPC Class Codes: C12N 2501/15 Transforming growth factor beta (TGF-β)
• CPC Class Codes: C12N 2501/16 Activin; Inhibin; Mullerian inhibiting substance
• CPC Class Codes: C12N 2501/415 Wnt; Frizzeled
• CPC Class Codes: C12N 2501/42 Notch; Delta; Jagged; Serrate
• CPC Class Codes: C12N 2502/09 epidermal cells, skin cells, oral mucosa cells
• CPC Class Codes: C12N 2502/13 connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
• CPC Class Codes: C12N 2502/256 Renal cells
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 2533/70 : Polysaccharides
• CPC Class Codes: C12N 2533/78 : Cellulose
• CPC Class Codes: C12N 5/0686 : Kidney cells
• CPC Class Codes: C12N 5/0697 : Artificial constructs associating cells of different lineages, e.g. tissue equivalents blood vessels C12N5/0691

Abstract

Provided are methods and compositions for constructing stable mammalian epithelial and/or endothelial tissues and organs. Disclosed are methods of using active epithelial and/or endothelial growth factors having the capability of effectuating induction of growth and morphogenesis of cells.

Claims

1. A method of generating an organ specific tubular tissue structure, comprising:

(a) contacting a stem cell, branching epithelial cell, or branching endothelial cell with one or more cell survival agents or biological active agents to stimulate growth and proliferation;

(b) contacting the cells with one or more branching agents that promotes formation of tubular tissue branches and/or globular morphology to generate budding tissue;

(c) combining the bud tissue with tissue specific mesenchyme in a biocompatible matrix; and

(d) culturing the combination to form an organ specific tubular tissue structure from which the tissue specific mesenchyme was obtain in vitro.

2. The method of claim 1, wherein the branching epithelial cell is a ureteric bud, bud or duct of a salivary gland, Wolffian duct bud, or ureteric and Wolffian duct bud tissue.

3. The method of claim 1, wherein the organ specific mesenchyme is from the group consisting of breast, pancreatic, lung, gall bladder, spleen, liver, and glandular mesenchyme.

4. The method of claim 3, wherein the glandular mesenchyme is selected from the group consisting of adrenal, salivary, prostate, thymus, parathyroid, pituitary, and pineal mesenchyme.

5. The method of claim 1, wherein the one or more cell survival agents are selected from the group consisting of FGF1, FGF7 and a combination thereof either alone or in combination with one or more of GDNF, PTN, HRG, or BSN-CM.

6. The method of claim 5, the one or more cell survival agents are selected from the group consisting of FGF1, FGF7, FGF1 and FGF7, PTN and GDNF, FGF1 and GDNF, FGF7 and GDNF, BSN-CM and FGF1, HRG and FGF1, PTN and FGF1, BSN and FGF7, HRG and FGF7, PTN and FGF7, BSN and FGF1 and GDNF, HRG and FGF1 and GDNF, PTN and FGF1 and GDNF, BSN and FGF7 and GDNF, HRG and FGF7 and GDNF, and PTN and FGF7 and GDNF.

7. The method of claim 1, wherein the one or more branching agents are selected from the group consisting of Fgf1, Fgf2, Fgf7, Fgf10, Hgf, Tgfα

, Activin, Bmp4, Tgfβ

, Gremlin1, ErbB/neuregulin/heregulin, Fgfr2, Egfr, Pax2, Eya1, Six1, Wnt4, Wnt5a, Wnt11, B-Catenin, Pea3/Etv4, Hs2st, MMP2, MT1-MMP, Fibronectin, Notch, Sonic Hedgehog, Sprouty1, Sprouty2, SFRP1, Semaphorin3a, Slit/Robo, and Eph/Ephrin.

8. The method of claim 1, wherein the biocompatible matrix comprises a material selected from the group consisting of a cotton, a collagen, a polyglycolic acid, a cat gut suture, a cellulose, a gelatin, a dextran, a polyamide, a polyester, a polystyrene, a polypropylene, a polyacrylate, a polyvinyl, a polycarbonate, a polytetrafluorethylene, a nitrocellulose compound, and a Matrigel.

9. The method of claim 8, wherein the biocompatible matrix is treated to contain proteoglycans, Type I collagen, Type IV collagen, laminin, proteoglycans, fibronectin, or combinations thereof.

10. The method of claim 1, further comprising culturing the budding tissue in vitro under conditions that induce branching morphogenesis to generate a population of tubular branches;

and subdividing the population of tubular branches; and

re-suspending each subpopulation in culture media and repeating.

11. A breast, pancreatic, lung, gall bladder, spleen, liver, reproductive, glandular or vascular tissue produced by the method of claim 1.

12. The method of claim 11, wherein the glandular tissue is selected from the group consisting of adrenal, salivary, prostate, thymus, parathyroid, pituitary, and pineal.

13. The tissue of claim 11, wherein the tissue is implanted into a subject so as to induce vascularization of the tissue.

14. A method to treat a disease, disorder or condition in a subject comprising implanting the tissue of claim 11 or a portion thereof in a subject.

15. The method of claim 14, wherein the disease, disorder or condition is selected from the group consisting of Sjogren syndrome, Addison'"'"'s disease, Celiac disease, chronic thyroiditis, multiple sclerosis, systemic lupus erythematosus, diabetes, pancreatitis, hypertension, chronic kidney disease, polycystic kidney disease, end stage renal disease, malignant hypertension, acute liver failure, chronic liver failure, chronic hepatitis infection, liver cirrhosis, hemochromatosis, Wilson'"'"'s disease, nonalcoholic steatohepatitis, hepatocellular carcinoma, hepatoblastoma, cholangiocarcinoma, biliary artesia, coronary artery disease, cardiomyopathy, heart failure, cystic fibrosis, emphysema, obstructive lung disease, short bowel syndrome, necrotizing enterocolitis, and Crohn'"'"'s disease.

16. A method to reconstruct tissue that has been removed from a subject comprising:

implanting the tissue of claim 11 or a portion thereof in a subject to replace damaged tissue that has been removed from the subject.

17. The method of claim 16, wherein the tissue that is replaced is breast tissue.

18. A test kit comprising a tissue of claim 11.

19. A method comprising:

differentiating stem cells to form tissue specific mesenchymal cells;

differentiating stem cells to form epithelial bud cells; and

combining the cells in a biocompatible matrix or gel; and

culturing the combination to form a specific tissue.