US 11,752,238 B2
Recapitulating the hematopoietic niche to reconstitute immunity
Nisarg J. Shah, Somerville, MA (US); Ting-Yu Shih, Brookline, MA (US); Angelo Mao, Somerville, MA (US); David J. Mooney, Sudbury, MA (US); and David T. Scadden, Weston, MA (US)
Assigned to President and Fellows of Harvard College, Cambridge, MA (US); and The General Hospital Corporation, Boston, MA (US)
Appl. No. 16/75,937
Filed by President and Fellows of Harvard College, Cambridge, MA (US); and The General Hospital Corporation, Boston, MA (US)
PCT Filed Feb. 6, 2017, PCT No. PCT/US2017/016729
§ 371(c)(1), (2) Date Aug. 6, 2018,
PCT Pub. No. WO2017/136837, PCT Pub. Date Aug. 10, 2017.
Claims priority of provisional application 62/292,288, filed on Feb. 6, 2016.
Prior Publication US 2019/0060525 A1, Feb. 28, 2019
Int. Cl. A61L 27/54 (2006.01); C12N 5/0789 (2010.01); A61L 27/20 (2006.01); A61L 27/52 (2006.01); A61L 27/56 (2006.01)
CPC A61L 27/54 (2013.01) [A61L 27/20 (2013.01); A61L 27/52 (2013.01); A61L 27/56 (2013.01); C12N 5/0647 (2013.01); A61L 2300/414 (2013.01); A61L 2300/426 (2013.01); A61L 2300/45 (2013.01); A61L 2400/18 (2013.01); A61L 2430/02 (2013.01); C12N 2501/155 (2013.01); C12N 2533/74 (2013.01)] 22 Claims
 
1. A composition comprising:
a porous implantable scaffold material;
one or more growth factors selected from the group consisting of BMP-2, BMP-4, BMP-6, BMP-12 and BMP-14; and
one or more differentiation factors selected from the group consisting of Delta-likel, Delta-1ike3, Delta-like4, Jagged1, and Jagged2, wherein the one or more differentiation factors are attached to the scaffold material and promote the differentiation of hematopoietic stem cells to lymphoid lineage cells; and
wherein the one or more growth factors are encapsulated in the scaffold material and are in an amount effective to promote the ectopic formation of bone tissue on or around the administered scaffold to form an ectopic bone marrow nodule for the infiltration and/or engraftment of hematopoietic stem cells.