IP Library › Granted Patent US 12,648,968
Granted Patent B2
US 12,648,968 · App. 17/753,491 · Granted Jun 9, 2026

Fibroblast and fibroblast-immunocyte combinations for treatment of subconcussive- and concussive-associated neurological damage

Inventor: Thomas Ichim (San Diego, CA)
Assignee: SPINALCYTE LLC
A61K35/33A61K35/15A61K35/28A61K38/177A61P25/00
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Quick Facts
Patent No.
US 12,648,968
App. No.
17/753,491
Granted
Jun 9, 2026
Kind
B2
Abstract

Embodiments of the disclosure include treatments of subconcussive and/or concussive brain damage by administering fibroblasts and/or fibroblasts cultured with one or more types of immunocytes. In one specific embodiment fibroblasts are cultured with monocytes in the presence of patient-specific T cells, and subsequently the T cells are re-administered into the patient. In one particular embodiment, products derived from fibroblast-immunocyte mixtures are comprised of cellular lysate, apoptotic bodies, exosomes, and/or other microvesicles. In one embodiment, the fibroblast cells and/or products derived from the fibroblast cells are administered subsequent to one or multiple head injuries. In other embodiments, products are administered in combination with neurorestorative and/or neuroprotective interventions.

Claims (64)

1 . A method of treating a sub-concussive or concussive brain injury in an individual, comprising the steps of: a) optionally identifying an individual with one or more elevated inflammatory markers subsequent to a head and/or neck injury; b) administering a therapeutically sufficient amount of regenerative cells and/or one or more products derived from said regenerative cells;

wherein said regenerative cells comprise fibroblasts, fibroblasts and hematopoietic stem cells (HSCs), fibroblasts and mesenchymal stem cells (MSCs), and/or fibroblasts and monocytes,

wherein the inflammatory markers are selected from the group consisting of: a) C-reactive protein; b) interleukin-1; c) interleukin-6; d) interleukin-8; e) interleukin- 33; f) erythrocyte sedimentation ratio; g) TNF-alpha; h) interferon-gamma; and i) a combination thereof,

wherein the inflammatory markers are elevated compared to an individual without a sub-concussive or concussive brain injury or a value in the general population,

wherein the one or more products derived from said regenerative cells comprise conditioned media, cellular lysate, apoptotic bodies, exosomes, microvesicles, or a combination thereof.

2 . The method of claim 1 , wherein the inflammatory markers are elevated at least 20% higher as compared to an individual without a sub-concussive or concussive brain injury or the value in the general population.

3 . The method of claim 1 , wherein said regenerative cells are fibroblasts.

4 . The method of claim 3 , wherein said fibroblast cells express a marker selected from the group consisting of Oct-4, Nanog, Sox-2, KLF4, c-Myc, Rex-1, GDF-3, LIF receptor, CD105, CD117, CD344 Stella, and a combination thereof.

5 . The method of claim 3 , wherein the fibroblast cells express a marker selected from the group consisting of CD10, CD13, CD44, CD73, CD90, CD141, PDGFr-alpha, HLA-A, HLA-B, HLA-C, and a combination thereof.

6 . The method of claim 3 , wherein the fibroblast cells do not express a marker selected from the group consisting of MHC class I, MHC class II, CD45, CD13, CD49c, CD66b, CD73, CD105, CD90, and a combination thereof.

7 . The method of claim 3 , wherein the fibroblast cells do not express a marker selected from the group consisting of CD31, CD34, CD45, CD117, CD141, HLA-DR, HLA-DP, HLA-DQ, and a combination thereof.

8 . The method of claim 1 , wherein said regenerative cells are a combination of fibroblasts with hematopoietic stem cells.

9 . The method of claim 8 , wherein said hematopoietic stem cells are capable of multi-lineage reconstitution in an immunodeficient host.

10 . The method of claim 8 , wherein said hematopoietic stem cells express the c-kit protein.

11 . The method of claim 8 , wherein said hematopoietic stem cells express the Sca-1 protein, express CD34, express CD133, lack expression of lineage markers, and/or lack expression of CD38.

12 . The method of claim 8 , wherein said hematopoietic stem cells are positive for expression of c-kit and Sca-1 and substantially lack expression of lineage markers.

13 . The method of claim 8 , wherein said hematopoietic stem cells are derived from a) peripheral blood; b) mobilized peripheral blood; c) bone marrow; d) cord blood; e) adipose stromal vascular fraction; f) derived from progenitor cells; or g) a combination thereof.

14 . The method of claim 1 , wherein said regenerative cells comprise mesenchymal stem cells and fibroblasts.

15 . The method of claim 14 , wherein said mesenchymal stem cells

(a) express a marker selected from the group consisting of: a) CD73; b) CD90; c) CD105; and d) a combination thereof;

(b) lack expression of a marker selected from the group consisting of: a) CD14; b) CD45; c) CD34; and d) a combination thereof; and/or

(c) are plastic adherent.

16 . The method of claim 14 , wherein said mesenchymal stem cells are derived from tissues selected from the group consisting of: a) bone marrow; b) peripheral blood; c) adipose tissue; d) mobilized peripheral blood; e) umbilical cord blood; f) Wharton's jelly; g) umbilical cord tissue; h) skeletal muscle tissue; i) subepithelial umbilical cord tissue; j) endometrial tissue; k) menstrual blood; 1 ) fallopian tube tissue; and m) a combination thereof.

17 . The method of claim 16 , wherein said mesenchymal stem cells

(a) are from umbilical cord tissue and express markers selected from the group consisting of; a) oxidized low density lipoprotein receptor 1, b) chemokine receptor ligand 3; c) granulocyte chemotactic protein; and d) a combination thereof; and/or

(b) are from umbilical cord tissue and do not express markers selected from the group consisting of: a) CD117; b) CD31; c) CD34; d) CD45; and e) a combination thereof; and/or

(c) are from umbilical cord tissue and express, relative to a human fibroblast, increased levels of interleukin 8 and/or reticulon 1; and/or

(d) are from umbilical cord tissue and have the potential to differentiate into cells of at least a skeletal muscle, vascular smooth muscle, pericyte or vascular endothelium phenotype; and/or

(e) are from umbilical cord tissue and express markers selected from the group consisting of: a) CD10; b) CD13; c) CD44; d) CD73; e) CD90; and f) a combination thereof.

18 . The method of claim 16 , wherein said umbilical cord tissue mesenchymal stem cell is an isolated umbilical cord tissue cell isolated from umbilical cord tissue substantially free of blood that is capable of self-renewal and expansion in culture.

19 . The method of claim 16 , wherein said umbilical cord tissue mesenchymal stem cells have the potential to differentiate into cells of other phenotypes.

20 . The method of claim 19 , wherein said other phenotypes comprise: a) osteocytic; b) adipogenic; c) chondrogenic differentiation or d) a combination thereof.

21 . The method of claim 16 , wherein

(a) said cord tissue-derived mesenchymal stem cells can undergo or has undergone at least 20 doublings in culture;

(b) said cord tissue-derived mesenchymal stem cell maintains a normal karyotype upon passaging;

(c) expresses a marker selected from the group consisting of: a) CD10 b) CD13; c) CD44; d) CD73; e) CD90; f) PDGFr-alpha; g) PD-L2; h) HLA-A,B,C; and i) a combination thereof;

(d) do not express one or more markers selected from the group consisting of a) CD31; b) CD34; c) CD45; d) CD80; e) CD86; f) CD117; g) CD141; h) CD178;

i) B7-H2; j) HLA-G; k) HLA-DR,DP,DQ; and 1) a combination thereof;

(e) secretes factors selected from the group consisting of: a) MCP-1; b) MIP1beta;

c) IL-6; d) IL-8; e) GCP-2; f) HGF; g) KGF; h) FGF; i) HB-EGF; j) BDNF; k) TPO; 1) RANTES; m) TIMP1; and n) a combination thereof;

(f) express markers selected from the group consisting of: a) TRA1-60; b) TRA1-81; c) SSEA3; d) SSEA4; e) NANOG; and f) a combination thereof;

(g) are positive for alkaline phosphatase staining; and/or

(h) are capable of differentiating into one or more lineages selected from the group consisting of a) ectoderm; b) mesoderm; c) endoderm; and d) a combination thereof.

22 . The method of claim 16 , wherein

(a) said bone marrow-derived mesenchymal stem cells possess markers selected from the group consisting of: a) CD73; b) CD90; c) CD105; and d) a combination thereof;

(b) said bone marrow-derived mesenchymal stem cells possess markers selected from the group consisting of: a) LFA-3; b) ICAM-1; c) PECAM-1; d) P-selectin; e) L-selectin; f) CD49b/CD29; g) CD49c/CD29; h) CD49d/CD29; i) CD29; j) CD18; k) CD61; 1) 6-19; m) thrombomodulin; n) telomerase; o) CD10; p) CD13; q) integrin beta; and r) a combination thereof; and/or (c) is a mesenchymal stem cell progenitor cell.

23 . The method of claim 22 , wherein said mesenchymal progenitor cells are a population of bone marrow mesenchymal stem cells expressing STRO-1.

24 . The method of claim 23 , wherein said mesenchymal progenitor cells express both STRO-1 and VCAM-1.

25 . The method of claim 23 , wherein said STRO- 1 expressing cells are negative for at least one marker selected from the group consisting of: a) CBFA-1; b) collagen type II; c) PPAR.gamma2; d) osteopontin; e) osteocalcin; f) parathyroid hormone receptor; g) leptin; h) H-ALBP; i) aggrecan; j) Ki67; k) glycophorin A; and 1) a combination thereof; and/or are positive for a marker selected from the group consisting of: a) VCAM-1; b) TKY-1; c) CD146; d) STRO-2; and e) a combination thereof.

26 . The method of claim 16 , wherein said bone marrow mesenchymal stem cells lack expression of CD14, CD34, and/or CD45.

27 . The method of claim 16 , wherein

(a) said bone marrow mesenchymal stem cell express markers selected from the group consisting of: a) CD13; b) CD34; c) CD56; d) CD117; and e) a combination thereof;

(b) do not express CD10;

(c) do not express one or more of CD2, CD5, CD14, CD19, CD33, CD45, and DRII; and/or

(d) express one or more of CD13,CD34, CD56, CD90, CD117 and nestin, and do not express one or more of CD2, CD3, CD10, CD14, CD16, CD31, CD33, CD45 and CD64.

28 . The method of claim 16 , wherein said skeletal mesenchymal stem cells express markers selected from the group consisting of a) CD13; b) CD34; c) CD56; d) CD117; and e) a combination thereof and/or wherein said skeletal muscle mesenchymal stem cells do not express CD10, CD2, CD5, CD14, CD19, CD33, CD45, and DRII.

29 . The method of claim 16 , wherein

(a) said subepithelial umbilical cord-derived mesenchymal stem cells express markers selected from the group consisting of a) CD29; b) CD73; c) CD90; d) CD166; e) SSEA4; f) CD9; g) CD44; h) CD146; i) CD105; and j) a combination thereof;

(b) said subepithelial umbilical cord-derived mesenchymal stem cells do not express markers selected from the group consisting of a) CD45; b) CD34; c) CD14; d) CD79; e) CD106; f) CD86; g) CD80; h) CD19; i) CD117; j) Stro-1;

k) HLA-DR; and 1) a combination thereof;

(c) express one or more of CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, and CD105;

(d) do not express one or more of CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, and HLA-DR; and/or

(e) are positive for OCT4 and/or SOX2.

30 . The method of claim 1 , further comprising a repeated administration of said regenerative cells and/or products derived from said regenerative cells.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 7, 2026
From: FIGENE, LLC
To: SPINALCYTE LLC
Reel/Frame 074595/0081 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2022
From: ICHIM, THOMAS
To: FIGENE, LLC
Reel/Frame 059169/0972 →
Continuity (2)
Provisional Application 62897428 · Sep 9, 2019
Related Publication 20220339201A1 · Oct 27, 2022
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