WCHR 2013 Topic Follicle neogenesis by DP Cells @Dr. Nigam's

[drnigams]

Kindly find below the abstract which was discussed at WCHR 2013 Edinburgh which I visited recently and had a interaction with Collin Jahoda on the same. Scientific minded members can discuss it further for hair follicle neogenesis

P220

Human hair follicle neogenesis using microvironmentally reprogrammed dermal papilla cells


click the below link for enlarge image

http://www.drnigams.net/images/poster/Large/1.JPG

click the below link for enlarge image

http://www.drnigams.net/images/poster/Large/2.JPG

CA Higgins, CA Jahods2 and AM christiano 1.3 Department of Dermatology, Columbia University, new York, USA , 2 Biological and Biomedical sciences, Durham University, Durham UK and 3 Genetics and Development, Columbia University, New York,USA

Hair Follicle (HF) neogensis refers to the generation of an entirely new HF in recipient skin using HF dermal papilla (DP) cells. This has been extensively demonstrated in rodent skin , either using intact DP or using intact Dp or using caltured DP cells. In contrast , HF neogensis in human skin has not previously been achieved using human cells. We performed global transcriptional profiling of both intact and cultured Dp cells using Affymetrix U133 Plus 2.0 array , which revealed several pathways expressed in intact5 DP , which are capable of neogenesis , but absent in caltured cells, that lack the micro environmental and anatomical context of intact DP is to grow the cells in hanging drops, which results in the formation of DP spheroids. We then profiled DP spheroids for changes in gene expression and determined that the average correlation coefficient between the transcriptomes of intact DP and the cultured cells is 0.42 , whereas that between the intact DP 3D culture. To evaluate whether recapitulation of the DP signature equated to a restored inductive potential, we established a contextual human – to – human HF neogenesis assay that could be used to assess the inductive capacity of human DP cells in human skin. When we micro implanted DP spheroids into recombined foreskins placed onto the back of SCID mice, we observed marked HF neogensis by 6 weeks, showing for the first time that intact human DP can induce de novo human HFs. We conclude that the partial restoration of the transcriptional profile in human Dp cells, achieved simply by growing the cells in a 3d spherical microenvironment, is sufficient in some instances to restore the inductive capacity of Dp cell cultures and elicit human HF neogenesis.P220

[UK Boy]

Question for Dr.Nigam about his London clinic

Hey Dr. Nigam

Just wondering what the latest news is in regards to you opening a clinic in London. You stated previously that you wouldbe in London in between the conferences in Scotland in order to finalise arrangements for your UK clinic. How did the meeting go? Please can you clarify again exactly what treatments you will be able to offer in your London clinic when it opens.

Thanks.

[drnigams]

UK,
My surgeon who is GMC,uk licensed will visit LONDON next week for consulting potential patients.He or patient counsellor will come once a month for consultations.
Which means in the first phase we will offer consultations at LONDON.We have a new comapaign..FLY BALD...FLY MUMBAI..where we take care of the patients stay and airfare as the visit for treatment at mumbai clinic.
I can offer doubling at LONDON in future..but now as on today because there is still lot of MPB research to be done..which takes away most of the time..i do not want to shift my focus..
Similarly my surgeon and or counsellors will visit top cities in months to come...
It makes sense to focus on cure and research..FLY BALD...FLY MUMBAI..would be the first step..so that my time is saved..at this point of time...
Idid had meetings which top 2 LONDON HT surgeons at HARLEY STREET,Few at edinburgh in the congress ,also saw few places at harley street,
I will exchange some mails with them(btw prices are exorbitant even for 3 staff run simple fue,7.5pounds per fue graft)..and i myself is not decided yet..whether to start my own or in partnership or train the local docs on doubling....but frankly..i want to focus on research..a lot of work still to be done..i do not want to be away from the lab..at least 6 months more...

Hey Dr. Nigam

Just wondering what the latest news is in regards to you opening a clinic in London. You stated previously that you wouldbe in London in between the conferences in Scotland in order to finalise arrangements for your UK clinic. How did the meeting go? Please can you clarify again exactly what treatments you will be able to offer in your London clinic when it opens.

Thanks.

[Pate]

Kindly find below the abstract which was discussed at WCHR 2013 Edinburgh which I visited recently and had a interaction with Collin Jahoda on the same. Scientific minded members can discuss it further for hair follicle neogenesis

P220

Human hair follicle neogenesis using microvironmentally reprogrammed dermal papilla cells


click the below link for enlarge image

http://www.drnigams.net/images/poster/Large/1.JPG

click the below link for enlarge image

http://www.drnigams.net/images/poster/Large/2.JPG

CA Higgins, CA Jahods2 and AM christiano 1.3 Department of Dermatology, Columbia University, new York, USA , 2 Biological and Biomedical sciences, Durham University, Durham UK and 3 Genetics and Development, Columbia University, New York,USA

Hair Follicle (HF) neogensis refers to the generation of an entirely new HF in recipient skin using HF dermal papilla (DP) cells. This has been extensively demonstrated in rodent skin , either using intact DP or using intact Dp or using caltured DP cells. In contrast , HF neogensis in human skin has not previously been achieved using human cells. We performed global transcriptional profiling of both intact and cultured Dp cells using Affymetrix U133 Plus 2.0 array , which revealed several pathways expressed in intact5 DP , which are capable of neogenesis , but absent in caltured cells, that lack the micro environmental and anatomical context of intact DP is to grow the cells in hanging drops, which results in the formation of DP spheroids. We then profiled DP spheroids for changes in gene expression and determined that the average correlation coefficient between the transcriptomes of intact DP and the cultured cells is 0.42 , whereas that between the intact DP 3D culture. To evaluate whether recapitulation of the DP signature equated to a restored inductive potential, we established a contextual human – to – human HF neogenesis assay that could be used to assess the inductive capacity of human DP cells in human skin. When we micro implanted DP spheroids into recombined foreskins placed onto the back of SCID mice, we observed marked HF neogensis by 6 weeks, showing for the first time that intact human DP can induce de novo human HFs. We conclude that the partial restoration of the transcriptional profile in human Dp cells, achieved simply by growing the cells in a 3d spherical microenvironment, is sufficient in some instances to restore the inductive capacity of Dp cell cultures and elicit human HF neogenesis.P220

This is MASSIVE news!! It seems to have escaped the forum quite how massive it is.

The reason Aderans, Replicel etc have underperformed expectations has long been suspected to be because DP/DSC cells lose their inductive capabilities when multiplied.

These HM technologies were expected to be available by now and capable of regenerating a full head of hair. They didn't, because of this problem.

Now Jahoda and his fellows have identified the cause of the problem and partially identified a solution. If they can solve it fully, we might finally be back on track.

[clandestine]

Thanks Pate. I feel a lot of this goes over our heads, mine included. Some clarification with regards to a more laymens explanation is always appreciated.

[SoClose]

This is great Dr. Nigam and thank you for your efforts.

However, I've said it once, and I'll say it again, dermal papilla cells losing their inductive potential is not a good thing.

[Arashi]

This is great Dr. Nigam and thank you for your efforts.

However, I've said it once, and I'll say it again, dermal papilla cells losing their inductive potential is not a good thing.

Eh ? The whole key here is that growing them in 3d spheres results in the DP cells (partially) retaining their inductive potential. The researchers think that it's only partial because of the 'lack of a hair epithelial influence in the assay" (these epithelial cells are normally adjacent to the DP cells). If they solve that problem too, then we're getting REALLY close

Anyway, this is indeed massive news and we're one really important step closer to a REAL cure !

[Arashi]

@Dr Nigams: Thanks for this ! But can you maybe review your text and correct the errors, since it makes it a bit hard to read now. For example it seems this sentence is lacking something:
"We then profiled DP spheroids for changes in gene expression and determined that the average correlation coefficient between the transcriptomes of intact DP and the cultured cells is 0.42 , whereas that between the intact DP 3D culture". And there are some more errors, it would be highly appreciated if you can review and correct the text. Thanks !

[SoClose]

Eh ? The whole key here is that growing them in 3d spheres results in the DP cells (partially) retaining their inductive potential. The researchers think that it's only partial because of the 'lack of a hair epithelial influence in the assay" (these epithelial cells are normally adjacent to the DP cells). If they solve that problem too, then we're getting REALLY close

Anyway, this is indeed massive news and we're one really important step closer to a REAL cure !

Ok, I'll try and remain positive. I just indulged in the sort of behaviour I despise. All we can do is wait. Or rally the FDA.

[Arashi]

In contrast , HF neogensis in human skin has not previously been achieved using human cells.

This I don't understand though. Isn't this exactly what Team Tokyo did ? They, just like these researchers, grew human HF on SCID mice. From what I understand the only difference is that Team Tokyo used existing DP cells, where these researches succeeded at using cultured DP cells (via growing them in 3d spheres). Which is of course a HUGE thing, since we need to be able to multiply these cells.

[Arashi]

Actually I was just reading back on Team Tokyo's work, and they used cultured DP cells as well ( http://www.gizmag.com/adult-stem-cel...therapy/22228/ ). So I'm not sure what's new here !?!

[534623]

So I'm not sure what's new here !?!

That's a good question: What's new here?

http://www.ncbi.nlm.nih.gov/pubmed/19761392

They, for example, said also in 2009 that they solved "a major technical obstacle" with DP cells.

So where is the cure??

[UK_]

So now that we have established that you need to use a 3D spheroid to grow follicles... will we have to wait ANOTHER 5 years?

And then when 5 years are up... they will come out with another reason why it hasnt worked and another method... then we will wait ANOTHER 5 YEARS....

We have been saying for years you need to use a 3D spheroid (we used to use the term scaffold on this site) so the cells know exactly what they're supposed to be doing. There was also member called HairTalk that used to say it all the time!

It's the reason why the DP cell injections are only working well in areas of diffuse thinning, because the [natural] scaffolds are already present in the scalp however after a very very long time of being bald the body destroys the (not in use) minaturized scaffolds (hair follicles), hence why slick bald regions wont grow hair with DP injections!

None of this is new, it can and does work, my only question is: why are we still waiting?

[Arashi]

Reading back Team Tokyo's work, it seems they grew human hair but on mouse skin. Jahoda et al grew it on human skin, transplanted onto SCID mice. So that's probably the difference.

[drnigams]

Arashi,
You are missing a few key new developments here,which are far ahead of tsujis work.

I listened to TSUJI'S lead researcher's presentation at WCHR,UK..Koh Tyoshima
FULLY FUNCTIONAL HAIR FOLLICLE REGEN THROUGH REARRANGEMENT OF STEMCELLS AND THEIR NICHES... How exactly did they do this?THE TSUJI LAB..
To produce the cells, the scientists undertook the following steps:
• Harvested epithelial stem cells and mesenchymal cells from adult mouse hair follicles.
• Growing the two cell types together, the team engineered “seed” hair follicles.
• When transplanted, these seed follicles made whisker-type hair.
• Turning to human cells, they collecting cells from the scalps of men with male pattern baldness.
• They then created a “seed” hair follicle by combining adult epithelial stem cells and dermal papilla cells from a normal mouse. Both cells types are basic cells that are found in the skin; dermal papilla are nipple-like projections at the base of hairs.
• The scientists then transplanted the cells into the back of mice genetically engineered to be bald.
• 28 bioengineered follicle germs were transplanted to a 1 centimeter- (0.39 inch-) circular patch of skin. This was meant to recreate what’s considered a normal hair density — about 120 hair shafts per square centimeter (0.15 square inch) or 60-100 hair shafts per square centimeter.


...and jahoda is talking about pure dp3d spheroidal culture injections and not adding any epithelial stemcells to create human hair follicle on sicd mouse with adrogenitic human skin..
That means jahoda is taliking about only use of dp /ds trichogenic cultured cells..and that to growing hair on human AGA skin..as against TSUJIlab...growing hair on genetically balded mouse skin..HUGE DIFFERENCE...

FOCUS IN REGEN OF HAIR FOLLICLE HAS SHIFTED FROM BULGE STEMCELL ...TO THIS NICHE...DP/DSC CELLS AND HOW TO HAVE THEM IN TRICHOGENIC/AGGREGATED/ENCAPSULATED STATE..NOW HAIR FOLLICLE CAN BE FORMED FROM HAIR SEED THAT IS DP/DSC..WITH OR WITHOUT EPITHELIAL STEMCELL INJECTION..ALTHOUGH MORE THE MERRIER ,HENCE I USE BOTH EPITHELIAL AND DP/DSC CULTURE...I AM LUCKY TO BE ONLY CLINIC OR PERSON IN THE WORLD INJECTING DP CULTURE ON REAL PATIENTS ..OTHERS ARE INJECTING ON MICE..AND FEW ON CLINICAL TRIAL...I CAN SEE IMPROVEMENT IN MY HM WITH DP CELL INJECTION...AND HOPE FUL OF FURTHER IMPROVEMENT WITH 3D SPHEROIDAL DP/DS CULTURE/AGGREGATEDCULTURE..SHORTLY..HAVE ALOOK AT A CASE OF PURE STEMCELL INJ RESULT I POSTED AT..THE OTHER FORUM

OTE=Arashi;123746]This I don't understand though. Isn't this exactly what Team Tokyo did ? They, just like these researchers, grew human HF on SCID mice. From what I understand the only difference is that Team Tokyo used existing DP cells, where these researches succeeded at using cultured DP cells (via growing them in 3d spheres). Which is of course a HUGE thing, since we need to be able to multiply these cells.[/QUOTE]