IP Library Granted Patent US 12,441,986
Granted Patent B2
US 12,441,986 · App. 17/559,583 · Granted Oct 14, 2025

Methods and compositions for the clinical derivation of a stem cell and therapeutic uses

Inventor: Amit Patel (Miami, FL)
Assignee: Jadi Cell LLC
C12N5/0682A61K35/51C12N5/0605C12N5/0653C12N5/0654C12N5/0655C12N5/0657
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,441,986
App. No.
17/559,583
Granted
Oct 14, 2025
Kind
B2
Abstract

Various cells, stem cells, and stem cell components, including associated methods of generating and using such cells are provided. In one aspect, for example, an isolated cell that is capable of self-renewal and culture expansion and is obtained from a subepithelial layer of a mammalian umbilical cord tissue. Such an isolated cell expresses at least three cell markers selected from CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, or CD105, and does not express at least three cell markers selected from CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, or HLA-DR.

Claims (14)

1. A method of making a plurality of isolated cells capable of self-renewal and culture expansion, comprising:

extracting isolated cells from a subepithelial layer of a mammalian umbilical cord being capable of self-renewal and culture expansion, further comprising;

removing Wharton's Jelly to expose the subepithelial layer of the mammalian umbilical cord; and

placing the subepithelial layer in contact with a growth substrate; and

and culturing the isolated cells in a culture medium to create the culture of isolated cells,

wherein the isolated cells express at least three cell markers selected from the group consisting of CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, or CD105, and

wherein the isolated cells do not express NANOG and do not express CD106, Stro-1, and CD117.

2. The method of claim 1 , further comprising opening the mammalian umbilical cord and wherein placing the subepithelial layer in contact with the growth substrate further comprises placing the mammalian cord interior side down in contact with the growth substrate.

3. The method of claim 1 , wherein placing the subepithelial layer in contact with the growth substrate further comprises placing the subepithelial layer in direct contact with the growth substrate.

4. The method of claim 1 , wherein extracting the isolated cells from the subepithelial layer and culturing the isolated cells in the culture medium are performed without the use of an enzyme.

5. The method of claim 1 , wherein extracting the isolated cells from the subepithelial layer and culturing the isolated cells in the culture medium are performed without the use of animal components.

6. The method of claim 1 , wherein the culture medium is derived from human-free and animal-free components.

7. The method of claim 1 , wherein the culture medium includes a platelet lysate.

8. The method of claim 1 , wherein the culture medium includes a lyophilized platelet rich plasma (PRP) lysate.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 21, 2023
From: PATEL, AMIT
To: JADI CELL LLC
Reel/Frame 063045/0145 →
Continuity (6)
Continuation 17322672 · May 17, 2021
Continuation 15799743 · Oct 31, 2017
Continuation 13732204 · Dec 31, 2012
Provisional Application 61591211 · Jan 26, 2012
Provisional Application 61582070 · Dec 30, 2011
Related Publication 20220251515A1 · Aug 11, 2022
References Cited (71)
US 8778679B2 · Silva et al. · 2014 [cited by applicant]
US 20100143312A1 · Hariri · 2010 [cited by applicant]
US 20210355437A1 · Gonzalez et al. · 2021 [cited by applicant]
JP 2008509699 · 2008 [cited by applicant]
WO WO2006019357A1 · 2006 [cited by applicant]
WO WO2010111522A2 · 2010 [cited by applicant]
Gonzalez et al., (2010) An efficient approach to isolation and characterization of pre-and postnatal umbilical cord lining stem cells for clinical applications. Cell Transplantation, 19(11), pp. 1359-1509 (Year: 2010). [cited by examiner]
Kita et al., (2010) Isolation and characterization of mesenchymal stem cells from the sub-amniotic human umbilical cord lining membrane. Stem Cells and Development, 19(4), pp. 491-501 (Year: 2010). [cited by examiner]
Kadivar et al.; “In Vitro Cardiomyogenic Potential of Human Umbilical Vein-Derived Mesenchymal Stem Cells;” Biochemical and Biophysical Research Communications; (Feb. 10, 2006); pp. 639-647; vol. 340, Issue 2. [cited by applicant]
Majore, et al., “Growth and Differentiation Properties of Mesenchymal Stromal Cell Populations Derived from Whole Human Umbilical Cord,” Stem Cell Rev. and Rep. (2011); 7:17-31. [cited by applicant]
Pierantozzi, et al., “Pluripotency Regulators in Human Mesenchymal Stem Cells: Expression of NANOG But Not of OCT-4 and SOX-2,” Stem Cells and Development (2011) vol. 20, No. 5, 915-923. [cited by applicant]
Riekstina, et al., “Embryonic Stem Cell Marker Expression Pattern in Human Mesenchymal Stem Cells Derived from Bone Marrow, Adipose Tissue, Heart and Dermis,” Stem Cell Reviews and Reports (2009) vol. 5, No. 4, 378-386. [cited by applicant]
Kogler, et al., “A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential,” J Exp Med 200:123-135 (2004). [cited by applicant]
Sensebe, “Clinical grade production of mesenchymal stem cells,” Biomed Mater Eng 18:S3-S10 (2008). [cited by applicant]
Wexler et al., “Adult bone marrow is a rich source of human mesenchymal ‘stem’ cells but umbilical cord and mobilized adult blood are not,” Br J Haematol 121:368-374 (2003). [cited by applicant]
Di Naro et al., “Umbilical cord morphology and pregnancy outcome,” Eur J Obstet Gynecol Reprod Biol 96:150-157 (2001). [cited by applicant]
Gang et al., “In vitro endothelial potential of human UC blood derived mesenchymal stem cells,” Cytotherapy 8:215-227 (2006). [cited by applicant]
Hou et al., “Induction of umbilical cord blood mesenchymal stem cells into neuron-like cells in vitro,” Int J Hematol 78:256-261 (2003). [cited by applicant]
Lee et al., “Isolation of multipotent mesenchymal stem cells from umbilical cord blood,” Blood 103:1669-1675 (2004). [cited by applicant]
Romanov et al., “Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord,” Stem Cells 21:105-110 (2003). [cited by applicant]
Bailey et al., “A comparison of human umbilical cord matrix stem cells and temporomandibular joint condylar chondrocytes for tissue engineering temporomandibular joint condylar cartilage,” Tissue Eng 13:2003-2010 (2007). [cited by applicant]
Conconi et al., “CD105(+) cells from Wharton's jelly show in vitro and in vivo myogenic differentiative potential,” Int J Mol Med 18:1089-1096 (2006). [cited by applicant]
Fu et al., “Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism,” Stem Cells 24:115-124 (2006). [cited by applicant]
Fu et al., “Transformation of human umbilical mesenchymal cells into neurons in vitro,” J Biomed Sci 11:652-660 (2004). [cited by applicant]
Karahuseyinoglu S et al., “Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys,” Stem Cells 25:319-331 (2007). [cited by applicant]
Lund et al., “Cells isolated from umbilical cord tissue rescue photoreceptors and visual functions in a rodent model of retinal disease,” Stem Cells 25:602-611 (2007). [cited by applicant]
Mitchell et al., “Matrix cells from Wharton's jelly form neurons and glia,” Stem Cells; 21:50-60 (2003). [cited by applicant]
Wang et al., “Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord,” Stem Cells 22:1330-1337 (2004). [cited by applicant]
Weiss et al., “Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease,” Stem Cells 24:781-792 (2006). [cited by applicant]
Baksh et al., “Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow,” Stem Cells 25:1384-1392 (2007). [cited by applicant]
Sarugaser et al., “Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors,” Stem Cells 23:220-229 (2005). [cited by applicant]
Kadner et al., “Human umbilical cord cells: a new cell source for cardiovascular tissue engineering,” Ann Thorac Surg 74:S1422-S1428 (2002). [cited by applicant]
Kadner et al., “Human umbilical cord cells for cardiovascular tissue engineering: a comparative study,” Eur J Cardiothorac Surg 25:635-641 (2004). [cited by applicant]
La Rocca et al., “Isolation and characterization of Oct-4+/HLAG+ mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers,” Histochem Cell Biol 131:267-282 (2009). [cited by applicant]
Freshney, Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6th ed Hoboken, NJ: Wiley-Blackwell; 2010; Chapter 11. [cited by applicant]
Parker et al., “Stem cells: shibboleths of development, part II: toward a functional definition,” Stem Cells Dev 14:463-469 (2005). [cited by applicant]
Horwitz et al. “Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement,” Cytotherapy 7:393-395 (2005). [cited by applicant]
Dominici et al., “Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement,” Cytotherapy 8:315-317 (2006). [cited by applicant]
Goodwin et al. “Multilineage differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat, and neural markers,” Biol Blood Marrow Transplant 7:581-588 (2001). [cited by applicant]
Chen et al., “Endothelial differentiation of Wharton's jelly derived mesenchymal stem cells in comparison with bone marrowderived mesenchymal stem cells,” Exp Hematol 37:629-640 (2009). [cited by applicant]
Pereira et al., “Reproducible methodology for the isolation of mesenchymal stem cells from human umbilical cord and its potential for cardiomyocyte generation,” J Tissue Eng Regen Med 2:394-399 (2008). [cited by applicant]
Martin-Rendon et al. “5-Azacytidine-treated human mesenchymal stem/progenitor cells derived from umbilical cord, cord blood and bone marrow do not generate cardiomyocytes in vitro at high frequencies,” Vox Sang 95:137-1… [cited by applicant]
Russell et al., “In vitro high-capacity assay to quantify the clonal heterogeneity in trilineage potential of mesenchymal stem cells reveals a complex hierarchy of lineage commitment,” Stem Cells 2010; 28:788-798. [cited by applicant]
Kuroda Y et al., “Unique multipotent cells in adult human mesenchymal cell populations,” Proc. Natl. Acad. Sci. USA 2010; 107:8639-8643. [cited by applicant]
Simpson et al., “Proteomics profiling of exosomes: Current perspectives,” Proteomics, 2008, 8, 4083-4099. [cited by applicant]
Camussi et al., “Exosomes/microvesicles as a mechanism of cell-to-cell communication,” Kidney International, 2010, 78, 838-848. [cited by applicant]
Ishige et al. “Comparison of mesenchymal stem cells derived from arterial, venous, and Wharton's jelly explants of human umbilical cord,” Int J Hematol; 90; pp. 261-269 (2009). [cited by applicant]
Era, Takumi et al. “Guided Differentiation from ES Cells to Mesodermal Cells,” Advances in Medicine, Jan. 13, 2007, vol. 220, No. 2, pp. 165-169. [cited by applicant]
Takaku, Fumimaro; Regeneration medicine-present states and future perspectives, Advances in Medicine, Feb. 3, 2001, vol. 196, No. 5, pp. 287-290. [cited by applicant]
Taylor, Nick Paul; “Mesoblast hit by FDS rejection, request to run another trial,” Fierce Bitotech online article, Oct. 2, 2020; pp. 1-5. [cited by applicant]
Mesoblast Briefing Documents for FDA; “Remestemcel-L for Treatment of Steroid Refractory Acute Graft Versus Host Diesease in Pediatric Patients,” Ongolgoic Drugs Advisory Committee; Aug. 31, 2020; 127 pages. [cited by applicant]
Rimes, Boe; “Therapeutic Solutions International Inc OTCMKTS: TSOI) Major Breakout as Biotech Sleeper Files Emergency Use Authorization (EUA) earlier this week to the FDA for JadiCells™M,” Therapeutic Solutions Internat… [cited by applicant]
Shapiro, Lindsey; “TSOI Seeks FDA OK to Launch Phase 1 Trial of Jadicell,” COPD News Today online article; May 12, 2022. [cited by applicant]
Rojewski, et al., “Phenotypic Characterization of Mesenchymal Stem Cells from Various Tissues,” Transfusion Medicine and Hemotherapy (2008), 35:168-184. [cited by applicant]
Raio et al., “Sonographic measurement of the umbilical cord and fetal anthropometric parameters,” Eur J Obstet Gynecol Reprod Biol 83:131-135 (1999). [cited by applicant]
Nanaev et al., “Stromal Differentiation and Architecture of the Human Umbilical Cord,” Placenta, 18, 53-64 (1997). [cited by applicant]
Gang et al., “Skeletal myogenic differentiation of mesenchymal stem cells isolated from human umbilical cord blood,” Stem Cells 22:617-624 (2004). [cited by applicant]
Panepucci et al., “Comparison of gene expression of umbilical cord vein and bone marrow-derived mesenchymal stem cells,” Stem Cells 22:1263-1278 (2004). [cited by applicant]
Schmidt et al., “Engineering of biologically active living heart valve leaflets using human umbilical cord-derived progenitor cells,” Tissue Eng 12:3223-3232 (2006). [cited by applicant]
Lu et al., “Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials,” Haematologica 91:1017-1026 (2006). [cited by applicant]
Wang et al., “Mesenchymal stem/progenitor cells in human umbilical cord blood as support for ex vivo expansion of CD34(+) hematopoietic stem cells and for chondrogenic differentiation” Haematologica 89:837-844 (2004). [cited by applicant]
Kolf, Catherine M.; “Biology of adult mesenchymal stem cells: regulation of niceh, self- renewal and differentiation,” Arthritis Researh & Therapy; Feb. 19, 2007; 9:204. [cited by applicant]
Ding, Dah-Ching et al.; “Mesenchymal Stem Cells,” Cell Translantation; vol. 20; pp. 5-14; 2011. [cited by applicant]
Lanzoni, Giacomo et al.; “Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial,” Stem Cells Translational Medicine, vol. 10, Iss… [cited by applicant]
Kouroupis, Dimitrios et al.; “Umbilical Cord-derived Mesenchymal Stem Cells modulate TNF and sTNFR2 in COVID-19 Ards patients,” Stem Cells Translation Medicine; 10.1002/sctm.20; Apr. 23, 2021. [cited by applicant]
Business Wire Article; “Therapeutic Solutions International Successfully Treats No OptionPatients with its Jadicell™M Stem Cell Therapy While Advancing Preparations for Phase III COVID-19 Clinical Trial”; Dec. 30, 2021. [cited by applicant]
Mills, Se; “Umbilical Cord,” Histology for Pathologists, 3 [cited by applicant]
Ernst, L. et al.; “Chapter 31 Placenta,” Color Atlas of Fetal and Neonatial Histoly, 1 [cited by applicant]
Can, Alp et al.; “Concise Review: Human Umbilical Cord Stroma with Regard to the Source of Fetus-Derived Stem Cells,” Stem Cells 25:2886-2895 (2007). [cited by applicant]
Pitrone, Maria et al.; “Knockdown of NANOG Reduces Cell Prolferation and Induces G0/G1 Cell Cycle Arrest in Human Adipose Stem Cells,” Int. J. Mol. Sci. 2019, 20, 2580; doi:10.3390/ijms20102580. [cited by applicant]
Saleh, Razwa et al.; “Short review on human umbilical cord lining epithelial cells and their potential clinical applications,” Stem Cell Research & Therapy (2017) 8:222. [cited by applicant]