WO2018125851A1 - Systèmes et procédés pour isoler et développer des cellules souches à partir d'urine - Google Patents
Systèmes et procédés pour isoler et développer des cellules souches à partir d'urine Download PDFInfo
- Publication number
- WO2018125851A1 WO2018125851A1 PCT/US2017/068380 US2017068380W WO2018125851A1 WO 2018125851 A1 WO2018125851 A1 WO 2018125851A1 US 2017068380 W US2017068380 W US 2017068380W WO 2018125851 A1 WO2018125851 A1 WO 2018125851A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cells
- urine
- stem cells
- therapeutic
- urine sample
- Prior art date
Links
- 210000002700 urine Anatomy 0.000 title claims abstract description 43
- 238000000034 method Methods 0.000 title claims abstract description 40
- 210000000130 stem cell Anatomy 0.000 title claims description 24
- 210000004027 cell Anatomy 0.000 claims description 35
- 230000008569 process Effects 0.000 claims description 17
- 239000001963 growth medium Substances 0.000 claims description 15
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 15
- 230000001225 therapeutic effect Effects 0.000 claims description 13
- 210000003734 kidney Anatomy 0.000 claims description 7
- 210000002966 serum Anatomy 0.000 claims description 5
- 239000006228 supernatant Substances 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 claims description 4
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 claims description 4
- 102100022464 5'-nucleotidase Human genes 0.000 claims description 3
- 241000283690 Bos taurus Species 0.000 claims description 3
- 102100037241 Endoglin Human genes 0.000 claims description 3
- 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 claims description 3
- 101000881679 Homo sapiens Endoglin Proteins 0.000 claims description 3
- 102100037362 Fibronectin Human genes 0.000 claims description 2
- 108010067306 Fibronectins Proteins 0.000 claims description 2
- 238000007865 diluting Methods 0.000 claims description 2
- 235000015097 nutrients Nutrition 0.000 claims description 2
- 230000008439 repair process Effects 0.000 claims description 2
- 244000134716 Hodgsonia macrocarpa Species 0.000 claims 1
- 230000003907 kidney function Effects 0.000 claims 1
- 210000000885 nephron Anatomy 0.000 claims 1
- 239000012472 biological sample Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000004113 cell culture Methods 0.000 description 4
- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 description 3
- 210000000577 adipose tissue Anatomy 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 238000005138 cryopreservation Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 210000005059 placental tissue Anatomy 0.000 description 2
- 210000003954 umbilical cord Anatomy 0.000 description 2
- 241000282412 Homo Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 238000013394 immunophenotyping Methods 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000000738 kidney tubule Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004409 osteocyte Anatomy 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000003668 pericyte Anatomy 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000005227 renal system Anatomy 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0662—Stem cells
- C12N5/0668—Mesenchymal stem cells from other natural sources
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/50—Proteins
- C12N2533/52—Fibronectin; Laminin
Definitions
- the invention is directed systems and methods to isolate stem cells from urine. BACKGROUND OF THE INVENTION
- MSCs Mesenchymal stem cells
- the invention is directed to a process to isolate stem cells from urine.
- the invention is directed to a method for collection, processing and therapeutic use of stem cells.
- the invention is directed to a business method for the collection, transport and use of urine derived mesenchymal stem cells.
- Fig 1A is a diagram of the renal system
- Fig IB illustrates stem cell originating site in the kidney.
- the invention is directed to a process to isolate stem cells from urine.
- the process includes the steps as provided in steps 1-9.
- Urine is centrifuged at 500-550g for 10 minutes to pellet all cells
- Cell culture growth medium is replaced the following day with fresh culture growth medium supplemented with K ⁇ g/ml Gentamicin sulfate; thereafter, growth medium is replaced every 2-3 days
- the process requires that 1) the urine samples are obtained by non-invasive methods 2) is limited to animal-free cell culture growth medium and 3) does not include bovine based serum. As the process uses animal free serum most regulatory concerns are avoided in addition to a further reduction of cost.
- the ability to obtain urine naturally or collection via an implemented catheter avoids the necessity to the cells by intrusive methods such as surgical or extraction by suction. Further, having the ability to obtain the cells by non-invasive methods substantially reduces costs and trauma to the patient.
- the cells derived from this process would be characterized by flow-based immunophenotyping against multiple positive and negative antigenic markers as well as differentiation assays to demonstrate the classic multipotency seen in MSCs. These cells would then be expanded under optimal culture conditions in an animal-free medium to provide commercialized production and application of urine-derived MSCs for various therapies, most specifically, autologous therapies within days or a couple of weeks of obtaining a sample.
- the process would not require isolation of MSCs from an encapsulating tissue matrix, digestive enzymes, or any of the things that the FDA regards as exceeding "minimal manipulation".
- UDMSCs urine-derived mesenchymal stem cells
- the invention is directed to a method for collection, processing and therapeutic use of stem cells including the steps of: a. obtaining a urine sample from a patient;
- the urine sample is obtained by a non-invasive method and uses only animal free serum.
- the expanded cells are stored at ambient temperatures. It is appreciated within the scope of the present invention, that it would be possible to provide therapeutic uses of stem cells which are obtained from a patient for use in another patient. However, those skilled in the art will appreciate the benefits of autologuous use.
- the invention is directed to a business method for the collection, transport and use of urine derived mesenchymal stem cells.
- Appendix A provides illustration and explanation regarding the process and characterization of the isolated stem cells and, in addition, the related steps regarding commercialization aspects for use of the cells.
- the business method includes the steps of: a. establishing a physician network with patients interested in therapeutic stem cell uses;
- processing the urine sample to isolate stem cells contained in the sample h. expanding the cells in a growth medium; and providing a therapeutic amount of the expanded cells as required to the patient from which the urine sample was obtained.
- MSCs derived from bone marrow, umbilical cord, placenta, and adipose tissue generally illustrate expression of the cell surface markers CD73, CD90, and CD105
- cells derived from urine illustrate very low or absent expression of CD73 and no detectable expression of CD105. These cells may illustrate positive or negative expression of CD90, suggesting that two cellular populations may be present.
- MSCs derived from bone marrow, umbilical cord, placenta, and adipose tissue are capable of differentiating into adipocytes, chondrocytes, and osteocytes
- UDMSCs near the end of their lifespans appear to differentiate into an epithelial-like phenotype with broad, flattened cells.
- UDMSCs are likely derived by shedding from kidney tubules suggesting that they have potential therapeutic application in kidney repair.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Developmental Biology & Embryology (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Microbiology (AREA)
- Public Health (AREA)
- Virology (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
L'invention concerne des procédés et des systèmes de collecte et de distribution de matériau d'échantillon biologique obtenu à partir d'urine humaine.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662439106P | 2016-12-26 | 2016-12-26 | |
US62/439,106 | 2016-12-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2018125851A1 true WO2018125851A1 (fr) | 2018-07-05 |
Family
ID=62710062
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2017/068380 WO2018125851A1 (fr) | 2016-12-26 | 2017-12-24 | Systèmes et procédés pour isoler et développer des cellules souches à partir d'urine |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2018125851A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021031884A1 (fr) * | 2019-08-20 | 2021-02-25 | 苏州吉美瑞生医学科技有限公司 | Procédé de culture de cellules souches rénales dérivées de l'urine et son utilisation |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070036767A1 (en) * | 2003-06-27 | 2007-02-15 | Ethicon, Incorporated | Postpartum cells derived from umbilical cord tissue, and methods of making and using the same |
WO2010065239A1 (fr) * | 2008-12-05 | 2010-06-10 | Wake Forest University Health Sciences | Cellules souches provenant d’urine et leurs procédés d’utilisation |
US20140248621A1 (en) * | 2012-01-10 | 2014-09-04 | John Collins | Microfluidic devices and methods for cell sorting, cell culture and cells based diagnostics and therapeutics |
-
2017
- 2017-12-24 WO PCT/US2017/068380 patent/WO2018125851A1/fr active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070036767A1 (en) * | 2003-06-27 | 2007-02-15 | Ethicon, Incorporated | Postpartum cells derived from umbilical cord tissue, and methods of making and using the same |
WO2010065239A1 (fr) * | 2008-12-05 | 2010-06-10 | Wake Forest University Health Sciences | Cellules souches provenant d’urine et leurs procédés d’utilisation |
US20140248621A1 (en) * | 2012-01-10 | 2014-09-04 | John Collins | Microfluidic devices and methods for cell sorting, cell culture and cells based diagnostics and therapeutics |
Non-Patent Citations (2)
Title |
---|
LITTLE, M.: "SBMB Showcase on Research: Generating Kidney Tissue from Pluripotent Stem Cells", AUSTRALIAN BIOCHEMIST, vol. 2, no. 1, 18 July 2016 (2016-07-18), pages 13, XP055607244 * |
MORAES, DA ET AL.: "A Reduction in CD 90 (THY-1) Expression Results in Increased Differentiation of Mesenchymal Stromal Cells", STEM CELL RESEARCH & THERAPY, vol. 7, no. 97, 28 July 2016 (2016-07-28), XP055404902 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021031884A1 (fr) * | 2019-08-20 | 2021-02-25 | 苏州吉美瑞生医学科技有限公司 | Procédé de culture de cellules souches rénales dérivées de l'urine et son utilisation |
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