Japan - Feb 2018 - Scale Production Of Biofabrication Of Hair Follicle For Regenerative Medicine

Noisette

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Hi guys :) A friend of Doctor Tsuji ? ;)

Here, I would like to share with you an another interested discovery? Anyone was aware about them ?

It's a lab in Faculty of Engineering, Yokohama National University, and the professor is Junji Fukuda

Their Objective
 Hair loss is a common disorder that affects men, women, and children due to aging, diseases, and medical treatments. Recent researches revealed that hair follicles can be regenerated by merging two aggregates composed of embryonic skin-derived epithelial cells and mesenchymal cells, and transplanting them intracutaneously. In this study, microfabrication approaches were employed for one-step preparation of a large number of epithelial and mesenchymal cell aggregates with a uniform diameter and spacing.

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Their study called " Spontaneous hair follicle germ (HFG) formation in vitro, enabling the large-scale production of HFGs for regenerative medicine" will be published this february 2018 in Biomaterials.

I share the whole PDF, you don't need to pay it.
https://www.sciencedirect.com/science/article/pii/S0142961217307214
Abstract
" Hair follicle morphogenesis is triggered by reciprocal interactions between hair follicle germ (HFG) epithelial and mesenchymal layers. Here, we developed a method for large-scale preparation of HFGs in vitro via self-organization of cells. We mixed mouse epidermal and mouse/human mesenchymal cells in suspension and seeded them in microwells of a custom-designed array plate. Over a 3-day culture period, cells initially formed a randomly distributed single cell aggregate and then spatially separated from each other, exhibiting typical HFG morphological features. These self-sorted hair follicle germs (ssHFGs) were shown to be capable of efficient hair-follicle and shaft generation upon intracutaneous transplantation into the backs of nude mice.
This finding facilitated the large-scale preparation of approximately 5000 ssHFGs in a microwell-array chip made of oxygen-permeable silicone.
We demonstrated that the integrity of the oxygen supply through the bottom of the silicone chip was crucial to enabling both ssHFG formation and subsequent hair shaft generation. Finally, spatially aligned ssHFGs on the chip were encapsulated into a hydrogel and simultaneously transplanted into the back skin of nude mice to preserve their intervening spaces, resulting in spatially aligned hair follicle generation. This simple ssHFG preparation approach is a promising strategy for improving current hair-regenerative medicine techniques
" .

" Generation of spatially aligned hair follicles
To examine the feasibility of simultaneously transplanting ssHFGs in a spatially aligned manner (Fig. 1B), mouse epithelial and mesenchymal cells (2-mL solution, 2.5 105 cells/mL of each cell type) were seeded into a HFG chip and cultured for 3 days. After aspirating the culture medium, 1 mL of type I collagen solution (3.0 mg/mL; Nitta Gelatin, Japan) was poured onto the HFG chip. To aid handling, a mechanical support mesh (Pip, Japan) was placed onto the chip and allowed to integrate into the collagen during the subsequent incubation (40 min, 37 C). The resulting collagen-gel sheet containing the two-dimensionally aligned ssHFGs was then peeled free of the HFG chip using tweezers. The gel sheet was cut to allow separation of the rows of ssHFGs so that they were able to be separately intracutaneously transplanted into the back skin of nu/nu mice. The transplanted skin was histologically stained after 21 days. "

" Conclusion
In the present study, we demonstrated the fabrication of a culture array chip for the large-scale preparation of ssHFGs via a twostep molding process. Seeding a mixture of dissociated epithelial and mesenchymal cells on this chip resulted in their selforganization to form aggregates and subsequent ssHFGs. The supply of adequate oxygen through the gas-permeable substrate used to fabricate the chip was demonstrated to be essential for the spontaneous self-organization of HFGs capable of generating hair shafts after transplantation into the back or scalp skin of nude mice. Regularly aligned hair follicles were generated by transferring ssHFGs from the chip via a collagen gel that enabled direct intracutaneous transplantation. Notably, the experiments conducted in the present study utilized murine cells, and thus, further studies of human trichogenic cells are required to assess the feasibility of this novel method for use in human hair-regenerative medicine. In fact, preliminary results generated in the present study showed that spontaneous cell separation and ssHFG formation could be achieved by seeding human keratinocytes and DP cells on the HFG chip. We hope to extend these preliminary analyses in the future in order to assess the suitability of this method to the culture of other potential human cell sources of both epithelial and dermal cell populations, such as bulge epithelial stem and keratinocyte precursor (epithelial) cells, as well as trichogenic dermal cells derived from stem or progenitor cells
."

source: https://www.sciencedirect.com/science/article/pii/S0142961217307214
source: http://www.fukulab.ynu.ac.jp/Research/research_ha01-en.html

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cheers :)
 

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dermrafok

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Indeed, I was right when I said that they were more advanced than previous publications. This is going very well. Thank you @Noisette . Great work.
 

Joxy

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So, can someone fluent in english and science message this doctor and ask specific questions? That will be awesome if they start clinical trials soon.
 

Hate da Bt

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Guys, this has little to do with Riken and their Organ Germ technology.
In this, embryonic murine stem cells were involved, whereas Tsuji's OG technology entails non-embryonic human stem cells.
The technology is similar, but the stem cells used are different.
 

That Guy

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I get sexually excited every time Noisette makes a thread. Great information, as always.

Guys, this has little to do with Riken and their Organ Germ technology.
In this, embryonic murine stem cells were involved, whereas Tsuji's OG technology entails non-embryonic human stem cells.
The technology is similar, but the stem cells used are different.

It actually has a lot to do with it, IMO because it covers both sides of the coin and further demonstrates the "if human cells work in murine models, human cells will work in humans" mantra that, for some baffling reason, people still doubt.

Personally, I now have zero doubts that this technology is going to be "it"; the thing most people will call a "cure". It is absolutely a viable method.

I just wish I was as optimistic about the prospects of many people being able to actually get this kind of treatment when it comes out, but that is beside the point.
 

sadila

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From a scientific standpoint, why is the hair that they grew on mouse is always in small samples ? Wouldn't it be more exciting to show a full NW1 mouse (lol) ?
 

Hate da Bt

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It actually has a lot to do with it, IMO because it covers both sides of the coin and further demonstrates the "if human cells work in murine models, human cells will work in humans" mantra that, for some baffling reason, people still doubt.

Personally, I now have zero doubts that this technology is going to be "it"; the thing most people will call a "cure". It is absolutely a viable method.
Not really.
This experiment was conducted on mice. The stem cells used were murine, not human and they were embryonic, to boot.
Tsuji has conducted experiments using human adult stem cells on mice.
The stem cells are different, the technology similar, though.
 

dermrafok

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Not really.
This experiment was conducted on mice. The stem cells used were murine, not human and they were embryonic, to boot.
Tsuji has conducted experiments using human adult stem cells on mice.
The stem cells are different, the technology similar, though.
Read this: "In fact, preliminary results generated in the present study showed that spontaneous cell separation and ssHFG formation could be achieved by seeding human keratinocytes and DP cells on the HFG chip. We hope to extend these preliminary analyses in the future in order to assess the suitability of this method to the culture of other potential human cell sources of both epithelial and dermal cell populations, such as bulge epithelial stem and keratinocyte precursor (epithelial) cells, as well as trichogenic dermal cells derived from stem or progenitor cells." "
 

Hate da Bt

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Read this: "In fact, preliminary results generated in the present study showed that spontaneous cell separation and ssHFG formation could be achieved by seeding human keratinocytes and DP cells on the HFG chip. We hope to extend these preliminary analyses in the future in order to assess the suitability of this method to the culture of other potential human cell sources of both epithelial and dermal cell populations, such as bulge epithelial stem and keratinocyte precursor (epithelial) cells, as well as trichogenic dermal cells derived from stem or progenitor cells." "
This proves my point.
They haven't tested yet their technology on human cells. Tsuji has.
 

d3nt3dsh0v3l

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Rip Mickey, did not know that :(
Lol gotta cut 'em open to see what happened inside.

This is what people forget when bitching about how long human trials take and how mice always get the cure first and how they would gladly volunteer to take the mouse's place.

Doesn't make sense to test in humans before animals. Can't have gene knockout humans for control. And oh yeah the mice are euthanized for collecting tissue samples and the like. And also for mercy.

You don't wanna be a mouse, lol.
 
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