Methods for Development and Use of Minimally Polarized Function Cell Micro-Aggregate Units in Tissue Applications Using LGR4, LGR5, and LGR6 Expressing Epithelial Stem Cells
Provided herein are constructs of micro-aggregate multicellular, minimally polarized grafts containing Leucine-rich repeat-containing G-protein coupled Receptor (LGR) expressing cells for wound therapy applications, tissue engineering, cell therapy applications, regenerative medicine applications, medical/therapeutic applications, tissue healing applications, immune therapy applications, and tissue transplant therapy applications which preferably are associated with a delivery vector/substrate/support/scaffold for direct application.
1 . A minimally polarized micro-aggregate multi-cellular composition, comprising: a multi-dimensional support selected from the group consisting of scaffolding, collagen, matrix, particle, and fiber, and isolated living LGR expressing cells.
2 . The composition of claim 1 further including growth factors and the LGR expressing cells being selected from the group consisting of LGR4, LGR5 and LGR6.
3 . The composition of claim 1 further including migratory/recruiting analytes and the LGR expressing cells being selected from the group consisting of LGR4, LGR5 and LGR6.
4 . The composition according to of claim 1 further including LGR specific binding elements selected from the group consisting of ligand families, R-spondin, EDGF, PDGF, Wnt, VEGF, and antimicrobial peptides and where the LGR expressing cells are selected from the group consisting of LGR4, LGR5 and LGR6.
5 . A composition according to claim 1 where the composition is used for a therapeutic construct for any one of a tissue region, wound, void, defect tissue, or blood.
6 . A composition according to claim 1 where the composition is used as a therapeutic construct for alteration of surrounding adjacent tissues.
7 . A composition according to claim 1 where the multi-dimensional support and isolated living LGR expressing cells providing a micro-aggregate multi-cellular construct for accelerated healing of wounds.
8 . A composition according to claim 1 where the multi-dimensional support and isolated living LGR expressing cells providing a micro-aggregate multi-cellular construct for tissue system repair or restoration throughout the body.
9 . A tissue graft comprising a composition according claim 1 for application to ectodermal, mesodermal or endodermal-derived tissues systems throughout a mammalian body.
10 - 24 . (canceled)
25 . The composition according to claim 3 further including LGR specific binding elements selected from the group consisting of ligand families, R-spondin, EDGF, PDGF, Wnt, VEGF, and antimicrobial peptides and where the LGR expressing cells are selected from the group consisting of LGR4, LGR5 and LGR6.
26 . A composition according to claim 3 where the composition is used for a therapeutic construct for any one of a tissue region, wound, void, defect tissue, or blood.
27 . A composition according to claim 3 where the composition is used as a therapeutic construct for alteration of surrounding adjacent tissues.
28 . A composition according to claim 3 where the multi-dimensional support and isolated living LGR expressing cells providing a micro-aggregate multi-cellular construct for accelerated healing of wounds.
29 . A composition according to claim 3 where the multi-dimensional support and isolated living LGR expressing cells providing a micro-aggregate multi-cellular construct for tissue system repair or restoration throughout the body.
30 . A tissue graft comprising a composition according to claim 3 for application to ectodermal, mesodermal or endodermal-derived tissues systems throughout a mammalian body.
31 . A composition according to claim 4 further characterized in that the composition is used for a therapeutic construct for any one of a tissue region, wound, void, defect tissue, or blood.
32 . A composition according to claim 4 further characterized in that the composition is used as a therapeutic construct for alteration of surrounding adjacent tissues.
33 . A composition according to claim 4 further characterized by the multi-dimensional support and isolated living LGR expressing cells providing a micro-aggregate multi-cellular construct for accelerated healing of wounds.
34 . A composition according to claim 4 further characterized by the multi-dimensional support and isolated living LGR expressing cells providing a micro-aggregate multi-cellular construct for tissue system repair or restoration throughout the body.
35 . A tissue graft comprising a composition according to claim 4 for application to ectodermal, mesodermal or endodermal-derived tissues systems throughout a mammalian body.
36 - 37 . (canceled)
38 . A composition comprising mammalian epithelial tissue, wherein the mammalian epithelial tissue is minimally polarized and comprises (i) epithelial stem cells expressing LGR and (ii) supportive cellular entities.
39 . The composition of claim 38 , wherein the LGR is selected from the group consisting of LGR4, LGR5, LGR6 or combinations thereof.
40 . The composition of claim 38 , wherein the supportive cellular entities are selected from the group consisting of cellular progenitor populations, stem cell populations, extracellular matrix elements, scaffolding elements, or combinations thereof.
41 . The composition of claim 38 , where in the epithelial stem cells are provided in the form of at least a portion of at least one follicular bulge.
42 . The composition of claim 38 , wherein the epithelial stems cells are provided in the form of a skin specimen comprising at least a portion of at least one follicular bulge and epidermal, dermal, and hypodermal tissue.
43 . The composition of claim 38 , further comprising one or more supplements selected from the group consisting of growth factors, analytes, LGR specific binding elements, or combinations thereof.
44 . The composition of claim 38 , further comprise an analyte selected from the group consisting of migratory analytes, recruiting analytes, or combinations thereof.
45 . The composition of claim 38 , further comprising a LGR specific binding element selected from the group consisting of ligand families, R-spondin, EDGF, PDGF, Wnt, VEGF, antimicrobial peptides, or combinations thereof.
46 . The composition of claim 38 , wherein the composition is capable of assembling a functional polarized tissue when transplanted to a target site.
47 . A pharmaceutical composition comprising the composition of claim 38 and a deliverable vehicle.
48 . A pharmaceutical composition comprising the composition of claim 38 and a multidimensional support.