Dr Lauster's Team (Berlin University of Technology)

[sdsurfin]

Hi Desmond. Thank you so much for doing this, especially so professionally.
I have a question for you or every other member that would be kind enough to answer it, if you donīt mind.
While looking at your post and watching the video, I asked myself if there is some sort of clear edge between vellus- and terminal hair. Is there some sort of trigger, or is it more like a longer process? It seems that the germans and Dr Gardner somehow disagree about this, at least in the eyes of a layman.
And if the germans would implant the vellus hair and it turns out to function perfectly. Wouldnīt that procedure only has to go through a safety trial, since it is some sort of HT? Thank you very much again.

I think that this is probably what most of the research teams are asking themselves. Nobody really has an answer for you, but it seems like the day is not too far off where they try to implant these neopapillae in a human scalp. The taiwanese are probably doing something very similar already. In my mind, there are still so many questions left, even if they do make a terminal hair in the lab. The sebaceous gland issue is one of them, but all in all the balding scalp just seems to be such an inhospitable environment. If the breakdown of the fat layer is so important, then what is going to stop the existing dying follicles from sending those signals and ruining the environment for the new follicles? Hopefully this technique will bring positive surprises, and not everything will be biologically set up against the new follicles. maybe they will improve the surrounding tissue. we can only hope. right now it's all still very speculative, but regenerating organs of all types in the lab seems to be a future certainty.

My guess is that when a follicle develops in the embryo, there is a constant stream over time of the right combinations of gorwth factors, nutrients, etc, that guide the HF cells to become a terminal hair. Even babies' hair is thin and wispy, it takes time for follicles to become mature. In that light, I don't know why it would be expected for hair follicles to create terminal hairs in the span of 14 days. Might it make sense to determine which growth factors are expressed just at that crucial moment when a baby's hair turns from wispy to full and terminal? I feel like the keys to the puzzle lie in that transition. i assume it would be hard to get baby scalp samples though

[sascha]

mmmmm I see, thanks for the reply. yes the thing with the baby scalp sounds very macabre hahahah but I think you are on to something, that jump from vellus to terminal seems critical.
Desmond did Dr Lindner or Dr Atac tell you about how much they improved exactly from 2011(clearly vellus) to 2013(????)..... I canīt really tell from the presentation ?!?!

[joachim]

they should definitely try to implant those micro follicles and see what happens after some weeks or months in human scalp. sd surfin brought up a good point with the fact that a terminal hair within 14 days maybe isn't even possible to develop.

all in all, i don't know what to think of TU Berlin's approach anymore. it all looks very promising with their biochip circulation and coating techniques etc. but in the end there is also a big chance that it could never produce good cosmetic results or overcome the problems with seb. gland. let's see what happens in the next 2 years and if they can achieve some progress.
maybe desmond saw some more details on their laptop which pointed into a more promising future. however, i'm still a bit dissapointed that there is not more progress since their first lab grown follicle in 2010. i think, we'll see similar findings and presentations during the next 3 years about DP culturing advancements but without any real indication for a cure. damn it

[sdsurfin]

they should definitely try to implant those micro follicles and see what happens after some weeks or months in human scalp. sd surfin brought up a good point with the fact that a terminal hair within 14 days maybe isn't even possible to develop.

all in all, i don't know what to think of TU Berlin's approach anymore. it all looks very promising with their biochip circulation and coating techniques etc. but in the end there is also a big chance that it could never produce good cosmetic results or overcome the problems with seb. gland. let's see what happens in the next 2 years and if they can achieve some progress.
maybe desmond saw some more details on their laptop which pointed into a more promising future. however, i'm still a bit dissapointed that there is not more progress since their first lab grown follicle in 2010. i think, we'll see similar findings and presentations during the next 3 years about DP culturing advancements but without any real indication for a cure. damn it

Yeah agreed. Seems like very slow progress. I think there's a lack of imagination, as the real hurdle seems to lie in how follicles develop at the neonatal stage. I'm kind of baffled at the fact that they can make a human lung, but not a hair follicle. There's something about the interaction of these cells that is missing, and I don't think any of these teams are onto the real key yet. That's just my hunch. Growth factors and spatial grouping seem to be important, but my guess is that there's a very specific (and possibly undecipherable) chain of chemical events that needs to happen, but also that the follicle needs a steady (and much more complete) avenue of nourishment and encouragement for much longer than 14 days to reach its full potential. Implantation of these seed germs is so crucial to understanding what they need, I really hope they get on it quickly. Desmond's news is encouraging, but could just as easily fall into the "in five years" promise. Just because we can imagine a solution doesn't mean it won't take another century to get there. If the progress over the past three years (basically almost nothing) is seen as an indication of the speed of things, theres no way we're anywhere close in terms of a cosmetic solution. hoping someone pulls out a miracle discovery.

[Armandein]

I'm kind of baffled at the fact that they can make a human lung, but not a hair follicle. .

Yes, but hair follicle is more complex that lung,..., than heart, and possibly even than brain ...... hair follicle or better pilosebaceous unit is very very complex, there is most of biological system of our, hormonal, circulatory, inmune, nervous, etce etc, more than a static miniorgan, it have stem cells to regrow after it lost, and even more complicated because it has Asynchronized hair cycle.....

..... It is more easy to grow in a lab a heart, a lung, a spleen, eye, or brain before we can make a simple? hair. But surely we can make great advances.

[Haircure]

Yes, but hair follicle is more complex that lung,..., than heart, and possibly even than brain ...... hair follicle or better pilosebaceous unit is very very complex, there is most of biological system of our, hormonal, circulatory, inmune, nervous, etce etc, more than a static miniorgan, it have stem cells to regrow after it lost, and even more complicated because it has Asynchronized hair cycle.....

..... It is more easy to grow in a lab a heart, a lung, a spleen, eye, or brain before we can make a simple? hair. But surely we can make great advances.

Not sure where you get your information from, but a hair follicle is no where near as complex as a heart, lungs or brain. The main reason why we can do all those things with other organs but not with hair follicles is very simple. Hair loss research is not something that is practiced and researched compared to other areas of medicine. Hair loss is a disease that is not seen as something urgent or of great importance as is something like cancer, heart disease, or neurological illnesses. It's very obvious that hair loss research is in it's infant stages compared to often prominent topics, as there are very few teams working on solutions to hair loss at the moment and regenerative medicine is not as widely practiced yet. Think about it, hair loss mostly occurs in men at a later age, where most are not likely to seek treatment or simply do not care. Hair loss doesn't yield any form of a morbidity or mortality statistic, so it's simply not as important.

[baldybald]

Not sure where you get your information from, but a hair follicle is no where near as complex as a heart, lungs or brain. The main reason why we can do all those things with other organs but not with hair follicles is very simple. Hair loss research is not something that is practiced and researched compared to other areas of medicine. Hair loss is a disease that is not seen as something urgent or of great importance as is something like cancer, heart disease, or neurological illnesses. It's very obvious that hair loss research is in it's infant stages compared to often prominent topics, as there are very few teams working on solutions to hair loss at the moment and regenerative medicine is not as widely practiced yet. Think about it, hair loss mostly occurs in men at a later age, where most are not likely to seek treatment or simply do not care. Hair loss doesn't yield any form of a morbidity or mortality statistic, so it's simply not as important.

well said

[Arashi]

I'm kind of baffled at the fact that they can make a human lung, but not a hair follicle.

That's just false. They can't grow a human lung yet. They can grow a 'mini lung' that somewhat functions like a lung. Exactly like they can grow mini hair follicles that somewhat function like hair follicles. Or a mini heart that somewhat functions like a heart. But they can't grow usuable organs yet, the only organ they've grown so far that was usuable was a trachea.

[Armandein]

Not sure where you get your information from, but a hair follicle is no where near as complex as a heart, lungs or brain. The main reason why we can do all those things with other organs but not with hair follicles is very simple. Hair loss research is not something that is practiced and researched compared to other areas of medicine. Hair loss is a disease that is not seen as something urgent or of great importance as is something like cancer, heart disease, or neurological illnesses. It's very obvious that hair loss research is in it's infant stages compared to often prominent topics, as there are very few teams working on solutions to hair loss at the moment and regenerative medicine is not as widely practiced yet. Think about it, hair loss mostly occurs in men at a later age, where most are not likely to seek treatment or simply do not care. Hair loss doesn't yield any form of a morbidity or mortality statistic, so it's simply not as important.

I know you say, " Hair loss doesn't yield any form of a morbidity or mortality statistic, so it's simply not as important"
but hair is complex in extrem, there is a interesting and free review

http://physrev.physiology.org/content/81/1/449.long

Molecular mediators of hair follicle growth

Some of its biological mediators involucrated are:
better to see in the link http://physrev.physiology.org/highwi...Chighwire_math


Factor Family Location in Follicle Function Reference No.
Growth, patterning, and transcription factors
Fibroblast growth factor (FGF)
 FGFR1 Papilla 385,482
 FGFR2 Matrix 482
 FGFR3 Precuticle cells of bulb
 FGFR4 IRS, ORS bulb periphery 482
 FGF1 Follicular epithelial cell 35, 100
 FGF2 Follicular epithelial cell Blocks follicle morphogenesis 35, 99
 FGF5 (short form) ORS Terminates anagen 179, 434,548, 549
 FGF5 (long form) Macrophage-like round cells in dermis Blocks short form
 FGF7 (KGF) Papilla Induces anagen; cytoprotective to chemotherapy 93, 152, 445
Sonic hedgehog (SHH)
 SHH Anagen bulb, IRS Initiates anagen 14, 28, 128, 233, 336, 383, 538a, 492
 PATCH Bulb and surrounding mesenchyme Mutation leads to basal cell carcinoma
Transforming growth factor-β  (TGF-β)
 TGF-β-RI ORS: late anagen/catagen Signal transducing receptor for TGF-β isoforms; plays a role in catagen development 123, 124, 411, 506,588
 TGF-βRII ORS: late anagen/catagen
 TGF-β1 TGF-β2 TGF-β3 All expressed in developing follicle; in mature follicle in IRS, ORS, and CTS TGF-β1 plays a role in catagen induction and blocks anagen induction in vivo and anagen growth in vitro; TGF-β1 and TGF-β2 stimulates ORS cell proliferation and opposes TGF-2 stimulus 123, 352, 436, 501, 584, 603
 BMP2 Anagen bulb prekeratogenous zone Suppresses proliferative activity and supports differentiation 30
 BMP4 Lower follicle mesenchyne Suppresses hair growth 28, 234, 538a
 BMP6 Epithelium Supports hair follicle development and growth 31
 Noggin Follicular mesenchyne Suppresses activity of BMP4 allowing for hair growth 38
WNT
 WNT-3 Prekeratogenous zone Hair shaft structure 336, 338, 571
 β-Catenin Keratogenous zone ORS Follicular morphogenesis 132, 618
 Lef-1 Peripapillary matrix 266
Epithelium and papilla cells
 Dishevelled-2 ORS; precursor cells and hair shift cortex and cuticle 336
Insulin-like growth factor (IGF)
 IGF-I Upper bulb Essential for follicle growth in vitro 210, 242, 300, 439, 486, 539
ORS
Anagen FP (but not catagen or telogen)
CTS
 IGF-I receptors Basal cell of the ORS, sebaceous gland, upper hair matrix keratinocytes 187
 IGFBP-3 IGFBP-5 FPFP, CTS Thought to play regulatory role on IGF expression 21, 180
 IGFBP-4 Papilla epithelial matrix margin, CTS 180
Epidermal growth factors  (EGF)
 EGF TGF-α Follicle morphogenesis stimulates cell growth in the ORS but inhibits it in the matrix 162, 302, 314, 335, 349, 350, 363, 437
 EGF-R In anagen ORS and matrix; in catagen on all undifferentiated cells of epithelial strand and secondary hair germ 98, 150
Hepatocyte growth factor  (HGF)
 HGF Papilla Mediates E-M interactions, stimulates follicle growth in vitro 227,228, 297, 509
 HGF receptor, c-met Follicular bulb epithelium Upregulation shows accelerated hair follicle morphogenesis and retarded entry to catagen 228,297
BRCA-1 Whisker placode and peg 274
Homeobox cluster genes
 HOX c8 HOX d9 HOX d11 HOX d12 Expression in matrix and papilla depending on gene Apparently imparting patterning character to the follicle and shaft 24, 243
 HOX d13 Hair matrix In KO mouse defective shaft 142
Agouti gene FP 337
Stem cell factor FP 183
MSX1MSX2 Epithelial placode; matrix of mature follicle 371, 465
A1x4 papilla 201
p53 Hair germ epithelium 501
Amphiregulin Bulbous hair peg, canal, bulge, FP, IRS 443
Platelet-derived growth factor  (PDGF)
 PDGF-A Matrix, hair germ epithelium 247, 386
 PDGF-B Matrix 5
 PDGF receptor FP 247
Winged helix nude
 Whn (nude) Follicular epithelium in differentiating cells of the hair follicle precortex, innermost cell layer of the ORS and a subclass of cells in the matrix Whn is a transcription factor that suppresses expression of differentiation genes; upregulating Whn prolongs anagen 53, 126, 280, 327,369, 459
Cytokines
Interferon Overexpression of IFN-α leads to hair loss 59
TNF-α ORS of developing follicle, CTS of late bulbous K14 driven overexpression leads to short, distorted hair follicles 69
Interleukins (IL)
IL-1α, IL-1β Epidermis, IRS, ORS, CTS, sebaceous glands, dermal vasculature, and arrrector pili muscle Upregulation leads to diminished and atrophic hair follicles; IL-1α and IL-1β inhibit hair growth in vitro 2, 33, 151,170, 189, 190, 311, 440
Other factors
Alkaline phosphatase In the papilla over the whole cycle, proximal ORS late anagen and early catagen Expressed in the mesenchyme of other regenerating systems 63, 161
PKA Inhibitors block hair follicle growth 171
PKC PKC is a negative regulator of hair growth; PKC inhibitors induce hair growth 111, 171-173, 550, 551
PKC-α Follicle fibroblasts and papilla cells but low in follicle epithelium; high in full anagen and low in telogen 191, 290
PKC-ζ High in follicle keratinocytes and low in papilla cells 191
PKC-δ Low in anagen and high in telogen 191, 290
Cyclin-dependent kinase inhibitors p21cip1/waf1 Differentiating cells of the epithelial follicles: shaft and IRS precursor cell but not in the ORS or bulb matrix 131, 453
Metallothionein Matrix cells, ORS but not papilla 246
Vitamin D receptor Expressed in ORS and papilla in late anagen (catagen) Mutated receptor results in alopecia in mice despite normal calcium levels; topical calcitriol in mice has a catagen-promoting effect 467, 623
Calcyclin Medulla and IRS of anagen hair follicles 605
Calcineurin
 Cyclosporin A FK506 Inhibits calcineurin and induces anagen, blocks onset of catagen, and gives some protection to chemotherapy-induced hair follicle damage 322, 409, 413, 426, 555,610
Hormones
PTHrp Viable epithelial portion of hair follicle Follicle morphogenesis antagonist PTH-(7—34)-amide increases hair growth, induces anagen, and provides some protection from chemotherapy-induced follicle damage 15, 195, 500, 608
PTHrp receptor Dermal fibroblasts 159
17β-Estradiol Blocks hair growth 374, 376
Estrogen receptor FP cell nuclei of telogen follicle Estrogen receptor antagonist induces anagen 376
Prolactin Receptor found in FP, matrix, ORS Stimulates anagen and catagen onset 72,430
Neurotrophin 3, neurotrophin  4, BDNF Complex hair cycle-dependent expression profile Promotes follicular morphogenesis, induces catagen in mature follicles 36, 37, 40,43, 46
Substance P binding sites FP 446
Retinoic acid receptors (RAR)
 RARα RARβ RARγ Papilla and epithelium of developing follicle 576
Androgen receptor FP cells 70, 210
Aromatase cytochrome ORS 494
5α-Reductase type 1 Sebaceous gland, ORS, FP, and CTS 22, 109, 495
5α-Reductase type 2 Follicular epithelium, interfollicular dermal cells, IRS, cuticles 22, 109, 495
KGF, keratinocyte growth factor; IGFBP, insulin-like growth factor binding protein; TGF, transforming growth factor; PKA, protein kinase A; PKC, protein kinase C; PTHrp, parathyroid hormone-related peptide; BDNF, brain-derived neurotrophic factor; ORS, outer root sheath; IRS, inner root sheath; FP, follicular papilla; BMP, bone morphogenic protein; CTS, connective tissue sheath of the follicle; BRCA, breast carcinoma gene.

[Armandein]

This is a muscle from lab

http://www.iflscience.com/technology/researchers-develop-muscle-powered-biorobots

hair in lab is more difficult .....

[sdsurfin]

lauster

Hey Desmond, What is Lauster's team doing about the DP cell challenge? Are they able to expand DPs and retain expression? Are they currently capable of expanding enough DP cells to effect a cure? Also, did it seem like they were interested in doing human trials with the neopapillae anytime soon? Did they talk about challenges related to the germs thriving in balding scalp? We got a lot of answers fron Dr. Gardner, but it feels as if implanting viable new hair germs is only half the problem, and you also need a cocurrent therapy to allow them to grow. Could you as lauster's team about that? To me it still seems like there are another ten years of testing and then probably another 8 or so of trials at least. You seem optimistic that the teams had other timelines in mind, but seriously, you can't just throw that out there and not explain....

[joachim]

man, i really have the feeling that there is a chance those vellus-like microfollicles would turn terminal after implantation. at least thicker than vellus if not full terminal.
as those are brand new follicles, they are not clogged by dht like the existing vellus hair in the scalp.
so, to produce a thick dark hair shaft the follicle needs the right nutrients, blood flow and oxygen. do the lauster team members exactly know what nutrients and how much of it they should feed the follicles, with the microchip environment?
all those nutrients would be delivered by the body after implanting those follicles.
so, in theory there is a good chance that one or the other of those implanted follicles could grow to a fully functional hair. maybe not every implanted hair, but 1 out of 10 would be good already.
i'm so afraid they will never try that out because they want to get the hair terminal in vitro alone. because one of their main goals is to develop the in-vitro hairs for testing purposes for cosmetics etc. so i think their first priority goal is not curing baldness.
i'm even not sure if they would be allowed to implant the microfollicles in patients without applying for official trials.

who knows if those micro follicles are not already the potential cure but many years might be wasted for further improvements in-vitro, where not necessary.

[joachim]

further i'm wondering about what details desmond saw on their notebook. as he saw the presentation of dr. atac already, what more impressive details could he have seen?
and does the presentation of dr. atac represent the latest progress or is it the status from last year?

[nameless]

man, i really have the feeling that there is a chance those vellus-like microfollicles would turn terminal after implantation. at least thicker than vellus if not full terminal.
as those are brand new follicles, they are not clogged by dht like the existing vellus hair in the scalp.
so, to produce a thick dark hair shaft the follicle needs the right nutrients, blood flow and oxygen. do the lauster team members exactly know what nutrients and how much of it they should feed the follicles, with the microchip environment?
all those nutrients would be delivered by the body after implanting those follicles.
so, in theory there is a good chance that one or the other of those implanted follicles could grow to a fully functional hair. maybe not every implanted hair, but 1 out of 10 would be good already.
i'm so afraid they will never try that out because they want to get the hair terminal in vitro alone. because one of their main goals is to develop the in-vitro hairs for testing purposes for cosmetics etc. so i think their first priority goal is not curing baldness.
i'm even not sure if they would be allowed to implant the microfollicles in patients without applying for official trials.

who knows if those micro follicles are not already the potential cure but many years might be wasted for further improvements in-vitro, where not necessary.

I think they should try injecting the follicles along with the correct adipose cells into the scalp and see what happens. I think it could actually a cure already the same as you think.

[Duke]

Hello my balding friends,

I have some news for you:

A couple days ago I asked Dr. Linders new company "Tissuse" how their work on hair follicels is going on and what they are planning to do next.

(Dr. Lindner is one of the Dr. Lauster / TU Berlin guys and Tissuse is the company that will commercialize TU Berlins work)


I was told that they are currently planning first "in-man-trials" - they also gave me Dr. Lindners email adress if I had more questions - so maybe we can collect some?!