WO1999001034A1 - Method for producing new hair growth - Google Patents
Method for producing new hair growth Download PDFInfo
- Publication number
- WO1999001034A1 WO1999001034A1 PCT/US1998/013754 US9813754W WO9901034A1 WO 1999001034 A1 WO1999001034 A1 WO 1999001034A1 US 9813754 W US9813754 W US 9813754W WO 9901034 A1 WO9901034 A1 WO 9901034A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- human
- dermal papilla
- papilla cells
- cells
- follicle
- Prior art date
Links
Classifications
-
- 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
- C12N5/0625—Epidermal cells, skin cells; Cells of the oral mucosa
- C12N5/0627—Hair cells
-
- 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
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/09—Coculture with; Conditioned medium produced by epidermal cells, skin cells, oral mucosa cells
- C12N2502/094—Coculture with; Conditioned medium produced by epidermal cells, skin cells, oral mucosa cells keratinocytes
Definitions
- the present invention is directed to a method for producing new hair growth in humans by implanting human dermal papilla cells into human scalp skin, wherein the human dermal papilla cells are cultured in a medium supplemented with a conditioned medium.
- the conditioned medium is formed from a culture of normal human keratinocytes.
- Hair loss is a very common human condition and many people desire treatment or correction for this problem.
- the leading cause for hair loss is the influence of androgens on genetically susceptible follicles (i.e. "androgenetic alopecia").
- Numerous treatments are available but all have significant drawbacks.
- Pharmacologic treatments attempt to revive and stimulate existing hair follicles. Because androgenetic alopecia may lead to the complete disappearance of hair follicles, pharmacologic treatments may always be of limited value.
- Hair restoration surgery involves the redistribution of permanent hair follicles to hairless areas but because the amount of hair follicles available for redistribution is limited, the ability of this teaching and to completely correct baldness is also limited.
- the purpose of the present invention is to overcome the limitations of the known treatments.
- a method of creating new follicles from existing follicles is needed, thus providing a virtually unlimited supply of hair for treating baldness.
- Previous research in rats has shown that hair follicles can actually be regenerated when the critical cellular component of the follicle, the papilla, is expanded using cell culture and transplanted into the skin (Jahoda CAB, Reynolds AJ, Oliver RF. Induction Of Hair Growth In Ear Wounds By Cultured Dermal Papilla Cells. J Invest Dermatol 101:584-590, 1993).
- One major limitation of this technique is that when the papilla cells are expanded in culture through serial passage, they lose their ability to regenerate hair.
- An object of the present invention is to provide a method of inducing hair growth in humans by implanting human dermal papilla cells into human skin.
- the method comprises the steps of removing a papilla from a human hair follicle, isolating the dermal papilla cells from the follicle to form a cell suspension, culturing such cells in a medium supplemented with a conditioned medium taken from human keratinocyte culture, and implanting the papilla cells so cultured into the epidermis layer of the skin in contact with an epidermal cell.
- Another object of the present invention is to provide a method for growing human dermal papilla cells in a medium supplemented with a conditioned medium that is formed by culturing human keratinocytes, taken from the epidermis of the follicle, for example, in the keratinocyte culture medium.
- the papilla cells so cultured can expand rapidly for many passages in vitro while maintaining their hair inducing properties.
- the implantation technique of the present invention is initiated by isolating and removing a papilla from the base of hair follicles from an area of a patient's scalp where hair loss is not expected to occur (e.g. the "donor area" used in hair transplantation comprising the mid temporo-parieto-occipital region of scalp).
- a papilla sample are obtained by a punch biopsy or an excisional technique similar to that used in hair transplantation in which tumescent anesthesia is used and the tissue is removed with strip or elliptical harvesting.
- the papilla is dissected free from the remaining part of the follicle, which is attached to and taken out together with the papilla, under microscopy.
- the dissected papilla is then initiated into a culture medium, either by simply floating the papilla in a medium containing a buffered salt solution with bovine serum to produce a cell suspension, or preferably, using a technique known to enhance the initiation of the papilla into culture (Warren R, Chestnut MH, Wong TK, et al. Improved Method For The Isolation And Cultivation Of Human Scalp Dermal Papilla Cells. J Invest
- the papilla cells are cultured in M199 or similar buffered salt solution with fetal calf serum in a concentration of 10 to 20% or in Chang's media, either of which may be supplemented with known papilla growth factors such as fibroblast, vascular endothelial, or platelet derived growth factors, and/or other known papilla stimulators.
- these media e.g. M199 with 10% fetal calf serum or Chang's media
- a conditioned medium formed from the culmres of normal human keratinocytes which are taken from the epidermis, or preferably from the outer root sheath of follicles, as described by Takashi M. et al.
- the keratinocytes are taken from the middle to lower portion of the follicles where the epithelial stem cells are thought to reside.
- the keratinocytes may be cultured in standard fashion but may also be treated with epithelial mitogens such as minoxidil or insulin-like growth factor.
- the source of these keratinocytes is from the same patient being treated (autologous source) but it may also be allogenic, such as from neonatal foreskin.
- the cells may be passed in a routine fashion.
- the use of keratinocyte conditioned media allows for the rapid expansion of papilla cells while maintaining their hair inducing properties. Therefore cells of low or high passage may be used, the latter being used to maximize cell number from a single papilla.
- the media containing animal sera is removed and the cells are incubated with or without the patient's autologous sera mixed in M199 or a similar salt solution.
- the papilla cells are harvested from the culture dish either by physically removing them or by enzymatic digestion such as with trypsin.
- the cells are either used directly or are subsequently aggregated such as with centrifugation.
- the cells may then be mixed with substances which can promote aggregation as well as easy introduction into the skin, such as fibronectin, glycosaminoglycans (e.g. dermatin sulphate, chondroitan sulfate, proteoglycans, heparan sulphate), collagen, and/or other substances known to fulfill this function.
- substances which can promote aggregation as well as easy introduction into the skin such as fibronectin, glycosaminoglycans (e.g. dermatin sulphate, chondroitan sulfate, proteoglycans, heparan sulphate), collagen, and/or other substances known to fulfill this function.
- the recipient site of the patient who is subject to the hair implantation may be pretreated with physical and/or pharmacologic methods to increase the receptiveness to the introduced cellular material.
- the physical methods include ultraviolet light, ultrasound, massage, or the like.
- Pharmacologic methods include topical minoxidil solution, or tretinoin solution or oral minoxidil, vitamins, or antioxidants, etc.
- the harvested papilla cells may then be introduced into the area of the skin subject to the implantation using various techniques. For example, the papilla cells may be introduced into a blister on the skin such as that formed by a suction device; or the cells may be introduced into slit incisions in the skin made with a scalpel blade or hypodermic needle.
- the cells may be introduced into the superficial layer of the skin by injection with a syringe and hypodermic needle.
- the amount of papilla cells for the implantation for each opening of the skin is preferably about 100,000, but may range from 1,000 to 1,000,000, depending on the size and depth of the opening and the overall viability and activity of the cells.
- the amount of the cells introduced may also be varied to vary the size of the subsequently produced hair.
- the papilla cells introduced into the skin opening by the above described implantation techniques are in physical contact with the native epidermal cells.
- the papilla cells may also be implanted by a co- introduction of a rigid shaft to promote the correct downward migration of the cells and proper orientation of the future follicle.
- an absorbable suture material such as poly gly colic, polyester, or polydioxanone, preferably coated with a substance known to promote cellular adhesion and migration, such as fibronectin, collagen, and/or glycosaminoglycans.
- the dermal papilla cells may be implanted together with epidermal cells, which are either interfollicular epidermal cells or those isolated from the outer root sheath of the follicle.
- epidermal cells are from the same patient being treated.
- the patient may be treated with either topical or systemic agents known to promote hair growth, including minoxidil, tretinoin, cyclosporine, finasteride, etc. Hair growth is expected over the subsequent weeks.
- dermal papilla cells at any stage are cryopreserved and therefore may be thawed and used at any time in the future.
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU82829/98A AU8282998A (en) | 1997-07-01 | 1998-07-01 | Method for producing new hair growth |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US5145997P | 1997-07-01 | 1997-07-01 | |
US60/051,459 | 1997-07-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1999001034A1 true WO1999001034A1 (en) | 1999-01-14 |
Family
ID=21971437
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1998/013754 WO1999001034A1 (en) | 1997-07-01 | 1998-07-01 | Method for producing new hair growth |
Country Status (2)
Country | Link |
---|---|
AU (1) | AU8282998A (en) |
WO (1) | WO1999001034A1 (en) |
Cited By (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001058413A1 (en) * | 2000-02-08 | 2001-08-16 | Klaus Rennebeck | Method for stimulating hair growth and kit for carrying out said method |
WO2002060396A2 (en) * | 2001-01-29 | 2002-08-08 | Aderans Research Institute, Inc. | Hair follicle neogenesis by injection of follicle progenitor cells |
WO2003051419A1 (en) * | 2001-12-19 | 2003-06-26 | Henkel Kommanditgesellschaft Auf Aktien | Skin/hair equivalent with reconstructed papillae |
WO2003088935A1 (en) * | 2002-04-17 | 2003-10-30 | Aderans Research Institute, Inc. | Compositions and methods for inducing new hair follicle formation and hair growth in a desired orientation |
US6817495B1 (en) | 1999-10-05 | 2004-11-16 | Mi-Ok Pty Ltd. | Portable tool box |
WO2005018731A1 (en) * | 2003-08-26 | 2005-03-03 | Alza Corporation | Device and method for intradermal cell implantation |
WO2005053763A1 (en) | 2003-12-05 | 2005-06-16 | Biointegrence Inc. | Hair growth method |
WO2007047707A1 (en) * | 2005-10-17 | 2007-04-26 | Aderans Research Institute, Inc. | Method of delivering hair follicle progenitor cells to the skin |
WO2005084223A3 (en) * | 2004-02-27 | 2007-05-31 | Gen Hospital Corp | Methods and compositions for hair growth |
EP1874265A2 (en) * | 2005-03-29 | 2008-01-09 | The Trustees of The University of Pennsylvania | Methods for generating new hair follicles, treating baldness, and hair removal |
US7354980B1 (en) | 2004-03-12 | 2008-04-08 | Key Medical Technologies, Inc. | High refractive index polymers for ophthalmic applications |
US7446157B2 (en) | 2004-12-07 | 2008-11-04 | Key Medical Technologies, Inc. | Nanohybrid polymers for ophthalmic applications |
US7780635B2 (en) | 2006-02-09 | 2010-08-24 | Aderans Research Institute, Inc. | Apparatus and methods for delivering fluid and material to a subject |
US7785876B2 (en) * | 2002-11-14 | 2010-08-31 | Aderans Research Institute, Inc. | Cultivation of hair inductive cells |
AU2012204059B2 (en) * | 2005-03-29 | 2015-01-15 | The Trustees Of The University Of Pennsylvania | Methods for generating new hair follicles, treating baldness and hair removal |
US8980628B2 (en) | 2006-03-17 | 2015-03-17 | Aderans Research Institute, Inc. | Hair follicle precursor production by co-culturing mammalian dermal papilla cells and keratinocytes |
US9023380B2 (en) | 2005-11-22 | 2015-05-05 | Aderans Research Institute, Inc. | Hair follicle graft from tissue engineered skin |
US11207511B2 (en) | 2010-12-06 | 2021-12-28 | Follica, Inc. | Methods for treating baldness and promoting hair growth |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4919664A (en) * | 1986-02-21 | 1990-04-24 | Oliver Roy F | Stimulation of hair growth |
US5130142A (en) * | 1990-10-31 | 1992-07-14 | The Practer & Gamble Company | Hair growth regulating composition comprising epithelium cell supernatant-derived growth factor |
EP0682107A2 (en) * | 1994-04-11 | 1995-11-15 | Research Development Corporation Of Japan | Method for the long term culturing of dermal papilla cells |
-
1998
- 1998-07-01 WO PCT/US1998/013754 patent/WO1999001034A1/en active Application Filing
- 1998-07-01 AU AU82829/98A patent/AU8282998A/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4919664A (en) * | 1986-02-21 | 1990-04-24 | Oliver Roy F | Stimulation of hair growth |
US5130142A (en) * | 1990-10-31 | 1992-07-14 | The Practer & Gamble Company | Hair growth regulating composition comprising epithelium cell supernatant-derived growth factor |
EP0682107A2 (en) * | 1994-04-11 | 1995-11-15 | Research Development Corporation Of Japan | Method for the long term culturing of dermal papilla cells |
Non-Patent Citations (3)
Title |
---|
JAHODA C. A. B., REYNOLDS A. J.: "DERMAL-EPIDERMAL INTERACTIONS. ADULT FOLLICLE-DERIVED CELL POPULATIONS AND HAIR GROWTH.", DERMATOLOGIC CLINICS., W.B. SAUNDERS CO., LONDON., GB, vol. 14., no. 04., 1 October 1996 (1996-10-01), GB, pages 573 - 583., XP002913549, ISSN: 0733-8635, DOI: 10.1016/S0733-8635(05)70385-5 * |
TAKASHI MATSUZAKI, MUTSUMI INAMATSU, KATSUTOSHI YOSHIZATO: "THE UPPER DERMAL SHEATH HAS A POTENTIAL TO REGENERATE THE HAIR IN THE RAT FOLLICULAR EPIDERMIS", DIFFERENTIATION., SPRINGER VERLAG., DE, vol. 60, no. 05, 1 September 1996 (1996-09-01), DE, pages 287 - 297, XP002913548, ISSN: 0301-4681, DOI: 10.1046/j.1432-0436.1996.6050287.x * |
WARREN R, WONG T K: "STIMULATION OF HUMAN SCALP PAPILLA CELLS BY EPITHELIAL CELLS", ARCHIVES OF DERMATOLOGICAL RESEARCH., SPRINGER, INTERNATIONAL, BERLIN., DE, vol. 286, no. 01, 1 January 1994 (1994-01-01), DE, pages 01 - 05, XP002913547, ISSN: 0340-3696, DOI: 10.1007/BF00375835 * |
Cited By (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6817495B1 (en) | 1999-10-05 | 2004-11-16 | Mi-Ok Pty Ltd. | Portable tool box |
WO2001058413A1 (en) * | 2000-02-08 | 2001-08-16 | Klaus Rennebeck | Method for stimulating hair growth and kit for carrying out said method |
WO2002060396A2 (en) * | 2001-01-29 | 2002-08-08 | Aderans Research Institute, Inc. | Hair follicle neogenesis by injection of follicle progenitor cells |
WO2002060396A3 (en) * | 2001-01-29 | 2003-03-13 | Bioamide Inc | Hair follicle neogenesis by injection of follicle progenitor cells |
WO2003051419A1 (en) * | 2001-12-19 | 2003-06-26 | Henkel Kommanditgesellschaft Auf Aktien | Skin/hair equivalent with reconstructed papillae |
WO2003088935A1 (en) * | 2002-04-17 | 2003-10-30 | Aderans Research Institute, Inc. | Compositions and methods for inducing new hair follicle formation and hair growth in a desired orientation |
US7785876B2 (en) * | 2002-11-14 | 2010-08-31 | Aderans Research Institute, Inc. | Cultivation of hair inductive cells |
JP2007503876A (en) * | 2003-08-26 | 2007-03-01 | アルザ・コーポレーシヨン | Devices and methods for intradermal cell transplantation |
WO2005018731A1 (en) * | 2003-08-26 | 2005-03-03 | Alza Corporation | Device and method for intradermal cell implantation |
EP1702632A4 (en) * | 2003-12-05 | 2009-11-11 | Biointegrence Inc | Hair growth method |
EP1702632A1 (en) * | 2003-12-05 | 2006-09-20 | Biointegrence Inc. | Hair growth method |
WO2005053763A1 (en) | 2003-12-05 | 2005-06-16 | Biointegrence Inc. | Hair growth method |
US7981629B2 (en) | 2004-02-27 | 2011-07-19 | The General Hospital Corporation | Methods of isolating dermal papilla cells |
US7476512B2 (en) | 2004-02-27 | 2009-01-13 | The General Hospital Corporation | Methods of identifying dermal papilla cells |
WO2005084223A3 (en) * | 2004-02-27 | 2007-05-31 | Gen Hospital Corp | Methods and compositions for hair growth |
US7354980B1 (en) | 2004-03-12 | 2008-04-08 | Key Medical Technologies, Inc. | High refractive index polymers for ophthalmic applications |
US7446157B2 (en) | 2004-12-07 | 2008-11-04 | Key Medical Technologies, Inc. | Nanohybrid polymers for ophthalmic applications |
US9056934B2 (en) | 2004-12-07 | 2015-06-16 | Key Medical Technologies, Inc. | Nanohybrid polymers for ophthalmic applications |
US7745555B2 (en) | 2004-12-07 | 2010-06-29 | Key Medical Technologies, Inc. | Nanohybrid polymers for ophthalmic applications |
US10421830B2 (en) | 2004-12-07 | 2019-09-24 | Key Medical Technologies, Inc. | Nanohybrid polymers for ophthalmic applications |
EP1874265A2 (en) * | 2005-03-29 | 2008-01-09 | The Trustees of The University of Pennsylvania | Methods for generating new hair follicles, treating baldness, and hair removal |
US9700502B2 (en) | 2005-03-29 | 2017-07-11 | The Trustees Of The University Of Pennsylvania | Methods for generating new hair follicles, treating baldness, and hair removal |
EP1874265A4 (en) * | 2005-03-29 | 2012-09-26 | Univ Pennsylvania | Methods for generating new hair follicles, treating baldness, and hair removal |
AU2012204059B2 (en) * | 2005-03-29 | 2015-01-15 | The Trustees Of The University Of Pennsylvania | Methods for generating new hair follicles, treating baldness and hair removal |
US9642789B2 (en) | 2005-03-29 | 2017-05-09 | The Trustees Of The University Of Pennsylvania | Methods for generating new hair follicles, treating baldness, and hair removal |
US9220926B2 (en) | 2005-03-29 | 2015-12-29 | The Trustees Of The University Of Pennsylvania | Methods for generating new hair follicles, treating baldness, and hair removal |
WO2007047707A1 (en) * | 2005-10-17 | 2007-04-26 | Aderans Research Institute, Inc. | Method of delivering hair follicle progenitor cells to the skin |
US9023380B2 (en) | 2005-11-22 | 2015-05-05 | Aderans Research Institute, Inc. | Hair follicle graft from tissue engineered skin |
US8206335B2 (en) | 2006-02-09 | 2012-06-26 | Aderans Research Institute, Inc. | Apparatus and methods for delivering fluid and material to a subject |
US7780635B2 (en) | 2006-02-09 | 2010-08-24 | Aderans Research Institute, Inc. | Apparatus and methods for delivering fluid and material to a subject |
US8980628B2 (en) | 2006-03-17 | 2015-03-17 | Aderans Research Institute, Inc. | Hair follicle precursor production by co-culturing mammalian dermal papilla cells and keratinocytes |
US11207511B2 (en) | 2010-12-06 | 2021-12-28 | Follica, Inc. | Methods for treating baldness and promoting hair growth |
Also Published As
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