OMG GUYS
The Japanese cracked the DP culturing problem in 2012 (most of the culturing problems anyways)! Somehow we missed it!!!
We have to get Christiano/Jahoda to collaborate with Dr Ohyama of Keio Univerity! These guys figured out how to mimic the epidermis making DP cells believe they are still within the skin even though they were harvested!!!
Here's the study:
Restoration of the intrinsic properties of human dermal papilla in vitro
Manabu Ohyama*, Tetsuro Kobayashi, Takashi Sasaki, Atsushi Shimizu and Masayuki Amagai
Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Accepted 1 May 2012
Journal of Cell Science 125, 4114–4125
2012. Published by The Company of Biologists Ltd
doi: 10.1242/jcs.105700
Summary
The dermal papilla (DP) plays pivotal roles in hair follicle morphogenesis and cycling. However, characterization and/or propagation of human DPs have been unsatisfactory because of the lack of efficient isolation methods and the loss of innate characteristics in vitro.
We hypothesized that culture conditions sustaining the intrinsic molecular signature of the human DP could facilitate expansion of functional DP cells. To test this, we first characterized the global gene expression profile of microdissected, non-cultured human DPs.
We performed a ‘two-step’ microarray analysis to exclude the influence of unwanted contaminants in isolated DPs and successfully identified 118 human DP signature genes, including 38 genes listed in the mouse DP signature. The bioinformatics analysis of the DP gene list revealed that WNT, BMP and FGF signaling pathways were upregulated in intact DPs and addition of 6-bromoindirubin-39-oxime, recombinant BMP2 and basic FGF to stimulate these respective signaling pathways resulted in maintained expression of in situ DP signature genes in primarily cultured human DP cells. More importantly, the exposure to these stimulants restored normally reduced DP biomarker expression in conventionally cultured DP cells. Cell growth was moderate in the newly developed culture medium.
However, rapid DP cell expansion by conventional culture followed by the restoration by defined activators provided a sufficient number of DP cells that demonstrated characteristic DP activities in functional assays. The study reported here revealed previously unreported molecular mechanisms contributing to human DP properties and describes a useful technique for the investigation of human DP biology and hair follicle bioengineering.
In summary, we have elucidated the molecular signature of intact human anagen DP cells. This guided the development of DPAC for the efficient in vitro expansion of human DP cells that retain their intrinsic properties. The present study sheds new light on the biological properties of human DP cells and implies a novel strategy for supplying sufficient functional human DP cells for the development of molecules acting on in vivo DPs or for regenerative medicine-based approaches to treat intractable hair loss disorders.
__________________________________________________ _______________
We are so much closer than we anticipated! We just have to make sure both teams are aware of each others work! We have to test the cultured Japanese DP cells on a foreskin grafted on a mice...if we get fully functional hair follicles...the entire balding community can celebrate. Because ladies and gentlemen, this curse is over!
I am more than certain, Tsuji lab is aware of these recent developments and I can guarantee you they are testing these DP cells in their labs as we speak
The Japanese cracked the DP culturing problem in 2012 (most of the culturing problems anyways)! Somehow we missed it!!!
We have to get Christiano/Jahoda to collaborate with Dr Ohyama of Keio Univerity! These guys figured out how to mimic the epidermis making DP cells believe they are still within the skin even though they were harvested!!!
Here's the study:
Restoration of the intrinsic properties of human dermal papilla in vitro
Manabu Ohyama*, Tetsuro Kobayashi, Takashi Sasaki, Atsushi Shimizu and Masayuki Amagai
Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Accepted 1 May 2012
Journal of Cell Science 125, 4114–4125
2012. Published by The Company of Biologists Ltd
doi: 10.1242/jcs.105700
Summary
The dermal papilla (DP) plays pivotal roles in hair follicle morphogenesis and cycling. However, characterization and/or propagation of human DPs have been unsatisfactory because of the lack of efficient isolation methods and the loss of innate characteristics in vitro.
We hypothesized that culture conditions sustaining the intrinsic molecular signature of the human DP could facilitate expansion of functional DP cells. To test this, we first characterized the global gene expression profile of microdissected, non-cultured human DPs.
We performed a ‘two-step’ microarray analysis to exclude the influence of unwanted contaminants in isolated DPs and successfully identified 118 human DP signature genes, including 38 genes listed in the mouse DP signature. The bioinformatics analysis of the DP gene list revealed that WNT, BMP and FGF signaling pathways were upregulated in intact DPs and addition of 6-bromoindirubin-39-oxime, recombinant BMP2 and basic FGF to stimulate these respective signaling pathways resulted in maintained expression of in situ DP signature genes in primarily cultured human DP cells. More importantly, the exposure to these stimulants restored normally reduced DP biomarker expression in conventionally cultured DP cells. Cell growth was moderate in the newly developed culture medium.
However, rapid DP cell expansion by conventional culture followed by the restoration by defined activators provided a sufficient number of DP cells that demonstrated characteristic DP activities in functional assays. The study reported here revealed previously unreported molecular mechanisms contributing to human DP properties and describes a useful technique for the investigation of human DP biology and hair follicle bioengineering.
In summary, we have elucidated the molecular signature of intact human anagen DP cells. This guided the development of DPAC for the efficient in vitro expansion of human DP cells that retain their intrinsic properties. The present study sheds new light on the biological properties of human DP cells and implies a novel strategy for supplying sufficient functional human DP cells for the development of molecules acting on in vivo DPs or for regenerative medicine-based approaches to treat intractable hair loss disorders.
__________________________________________________ _______________
We are so much closer than we anticipated! We just have to make sure both teams are aware of each others work! We have to test the cultured Japanese DP cells on a foreskin grafted on a mice...if we get fully functional hair follicles...the entire balding community can celebrate. Because ladies and gentlemen, this curse is over!
I am more than certain, Tsuji lab is aware of these recent developments and I can guarantee you they are testing these DP cells in their labs as we speak
VERY nice find Desmond. Perhaps this method combined with Jahoda's 3D culture approach would do the trick. The only thing this paper did not do was test it in human tissue, right?
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