IP Library Granted Patent US 12,465,669
Granted Patent B2
US 12,465,669 · App. 18/164,308 · Granted Nov 11, 2025

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

Inventor: Denver M. Lough (Salt Lake City, UT)
Assignee: GRANDER ACQUISITION LLC
A61L27/3813A01N1/122A01N1/125A61L27/54C12N5/0625A61L2300/412A61L2430/00C12N2513/00
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Quick Facts
Patent No.
US 12,465,669
App. No.
18/164,308
Granted
Nov 11, 2025
Kind
B2
Abstract

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.

Claims (29)

1 . A composition, comprising:

a first tissue section comprising a dermal segment, an epidermal segment, and a segment of a follicular unit of a mammalian cutaneous tissue specimen, wherein the dermal segment and the epidermal segment are outside the follicular unit; the segments are interconnected; and the segment of the follicular unit comprises living LGR-expressing stem cells that are exposed; and

a second tissue section separated from the first tissue section, the second tissue section consisting of a second dermal segment and a second epidermal segment, wherein the second dermal segment and second epidermal segment are interconnected;

wherein the composition is capable of regenerating functional tissue comprising epidermis, dermis, and appendages when transplanted to a damaged tissue site in a subject in need thereof.

2 . The composition of claim 1 , wherein the mammalian cutaneous tissue specimen is a human cutaneous tissue specimen.

3 . The composition of claim 1 , further comprising a cell sustaining media.

4 . The composition of claim 3 , wherein the cell sustaining media comprises pulse rescue media.

5 . The composition of claim 1 , further comprising one or more supplements selected from growth factors, LGR specific binding elements, or combinations thereof.

6 . The composition of claim 5 , wherein the LGR specific binding elements are selected from the group consisting of R spondin, an epidermal-derived growth factor (EDGF), a platelet-derived growth factor (PDGF), a Wnt protein, a vascular endothelial growth factor (VEGF), an antimicrobial peptide, and combinations thereof.

7 . The composition according to claim 1 , wherein the living LGR-expressing stem cells are LGR4-expressing cells, LGR5-expressing cells, LGR6-expressing cells, or any combination thereof.

8 . The composition of claim 1 , further comprising processed fat and hypodermal elements.

9 . A pharmaceutical composition comprising the composition of claim 1 and a deliverable vehicle.

10 . A pharmaceutical composition comprising the composition of claim 1 and a multidimensional support.

11 . The composition of claim 1 , wherein the segment of the follicular unit comprises a segment of a bulge.

12 . The composition of claim 1 , wherein the segment of the follicular unit comprises a segment of a bulb.

13 . A composition, comprising:

a tissue section comprising a dermal segment, an epidermal segment, and a segment of a follicular compartment of a mammalian cutaneous tissue specimen, wherein the segments are interconnected and the segment of the follicular compartment comprises living LGR-expressing stem cells that are exposed;

wherein the composition is prepared by a process comprising separating fat and hypodermal elements from the mammalian cutaneous tissue specimen ex vivo to provide remaining cutaneous elements containing an epidermal compartment, a dermal compartment, and the follicular compartment; and segmenting the epidermal compartment, the dermal compartment, and the follicular compartment to open the follicular compartment and prepare the tissue section, and the composition is capable of regenerating functional tissue comprising epidermis, dermis, and appendages when transplanted to a damaged tissue site in a subject in need thereof.

14 . The composition of claim 13 , further comprising a second tissue section comprising a second dermal segment and a second epidermal segment, wherein the second dermal segment and the second epidermal segment are interconnected.

15 . The composition of claim 13 , wherein the mammalian cutaneous tissue specimen is a human cutaneous tissue specimen.

16 . The composition of claim 13 , further comprising a cell sustaining media.

17 . The composition of claim 16 , wherein the cell sustaining media comprises pulse rescue media.

18 . The composition of claim 13 , further comprising one or more supplements selected from growth factors, LGR specific binding elements, or combinations thereof.

19 . The composition of claim 18 , wherein the LGR specific binding elements are selected from the group consisting of R spondin, an epidermal-derived growth factor (EDGF), a platelet-derived growth factor (PDGF), a Wnt protein, a vascular endothelial growth factor (VEGF), an antimicrobial peptide, and combinations thereof.

20 . The composition according to claim 13 , wherein the living LGR-expressing stem cells are LGR4-expressing cells, LGR5-expressing cells, LGR6-expressing cells, or any combination thereof.

21 . A pharmaceutical composition comprising the composition of claim 13 and a deliverable vehicle.

22 . A pharmaceutical composition comprising the composition of claim 13 and a multidimensional support.

23 . The composition of claim 13 , wherein the segment of the follicular compartment comprises a segment of a bulge.

24 . The composition of claim 13 , wherein the segment of the follicular compartment comprises a segment of a bulb.

Assignments (3)
SECURITY INTEREST Recorded May 17, 2024
From: GRANDER ACQUSITION LLC
To: AVENUE VENTURE OPPORTUNITIES FUND, L.P., AS AGENT
Reel/Frame 067452/0616 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 15, 2023
From: POLARITYTE, INC. (PTE); POLARITYTE MD, INC. (PTE MD); POLARITYTE, INC. (PTE NV)
To: GRANDER ACQUISITION LLC
Reel/Frame 064597/0228 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 6, 2023
From: LOUGH, DENVER M., DR.
To: POLARITYTE, INC.
Reel/Frame 062890/0615 →
Continuity (6)
Continuation 17723748 · Apr 19, 2022
Continuation 17326734 · May 21, 2021
Continuation 15650656 · Jul 14, 2017
Division 14954335 · Nov 30, 2015
Provisional Application 62086526 · Dec 2, 2014
Related Publication 20230181797A1 · Jun 15, 2023
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