Production of a bioengineered lung
AssigneeBoard of Regents, The University of Texas System
InventorsJoaquin CORTIELLA, Joan E. NICHOLS, Jean NILES, Saverio LAFRANCESCA, Jason SAKAMOTO
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Abstract
The present invention provides processes for producing a bioengineered lung (BEL) from an acellular lung matrix that has been treated with growth hormones, seeded with primary lung cells, and cultured in a bioreactor. Also provided are BELs and methods of transplanting the BEL into a subject in need of a lung transplant, and methods for using BELs for the study of the lung microbiome and its role in lung development and remodeling.
Claims43
A method for producing a bioengineered lung (BEL) comprising:
- (a) obtaining an acellular (AC) lung scaffold;
- (b) treating the AC lung scaffold with one or more growth factors;
- (c) seeding the treated AC lung scaffold with primary lung cells;
- and
- (d) culturing the seeded AC lung scaffold in a bioreactor to produce the BEL.
The method of any one of the foregoing claims, wherein said primary lung cells are obtained from a biopsy or pneumonectomy of lung which biopsy or pneumonectomy optionally is pretreated with dextrose prior to decellularization wherein decellularization optionally is effected using sodium dodecyl sulfate (SDS).
The method of any one of the foregoing claims, wherein the BEL is suitable for transplantation into an autologous, allogeneic or xenogeneic recipient.
The method of any one of the foregoing claims, wherein step (b) comprises treating the AC lung scaffold with one or more growth factors and platelet rich plasma which promote angiogenesis and the functionality of the BEL after transplantation.
The method of any one of the foregoing claims, wherein step (b) comprises treating the AC lung scaffold with one or more growth factors at least some of which are loaded onto microparticles or nanoparticles and/or are delivered using a hydrogel.
The method of any one of the foregoing claims, wherein step (b) comprises treating the AC lung scaffold with VEGF, FGF2, KGR, or any combination thereof.
The method of any one of the foregoing claims, wherein step (b) comprises treating the AC lung scaffold with VEGF and FGF2.
The method of any one of the foregoing claims, wherein step (b) comprises treating the AC lung scaffold with microparticles or nanoparticles comprising VEGF and a hydrogel comprising FGF2.
The method of any one of the foregoing claims, wherein step (b) comprises treating the AC lung scaffold with microparticles or nanoparticles comprising VEGF and a hydrogel comprising FGF2, a hydrogel comprising KGR, and a hydrogel comprising platelet rich plasma.
The method of any one of the foregoing claims, wherein the primary lung cells comprise primary vascular cells.
The method of any one of the foregoing claims, wherein the BEL is cultured on the AC lung scaffold for about 30 days or more prior to transplantation into a recipient.
The method of any one of the foregoing claims, wherein the immune system of the BEL is reconstituted by the addition of mononuclear leukocytes (MNLs), optionally autologous, to the bioreactor culture optionally at about day 11 of culture.
The method of any one of the foregoing claims, wherein the immune system of the BEL is reconstituted by the addition of serum, alveoloar macrophages (AMs) and mononuclear leukocytes (MNLs), optionally autologous, to the bioreactor culture optionally around day 30 prior to transplant.
The method of any one of the foregoing claims, wherein step (b) comprises treating the AC lung scaffold with microparticles or nanoparticles comprising one or more growth factors, wherein said microparticles or nanoparticles comprise a mixture of microparticles or nanoparticles having a pore size of 60 nm and microparticles or nanoparticles having a pore size of 30 nm.
A method for producing a bioengineered lung (BEL) having a reconstituted immune system, comprising:
- (a) obtaining an acellular (AC) lung scaffold;
- (b) seeding the treated AC lung scaffold with primary lung cells;
- and
- (c) culturing the seeded AC lung scaffold in a bioreactor to produce the BEL, wherein step (c) comprises adding immune cells to the BEL during culturing in order to reconstitute the immune system.
A BEL produced by the method of any one of the foregoing claims.
Dependencies are inferred from the claim text.