Fifth International Congress of Hair Research

Stem cell; cell based hair therapy
1

I noticed this posted on another site
http://www.nahrsmembers.org/home/Portals/0/meetings_support/abstracts_5th_congress/Final_Program_from_Bristol.pdf

Lots of great speakers. For example

Page 25
Hair Follicle Stem Cells – Epithelial
Speaker: George Cotsarelis, MD
University of Pennsylvania, Philadelphia, PA, USA
Over 15 years ago, we proposed that quiescent keratinocytes in the hair follicle bulge were epithelial stem cells important for hair follicle cycling, epidermal renewal, wound healing and carcinogenesis. Since that time, we identifi ed cytokeratin 15 (K15) expression as a marker for these cells and developed several transgenic mouse models using the K15 promoter to further study the bulge cells. Using K15-EGFP mice, we isolated bulge cells and demonstrated that they possessed an epithelial stem cell phenotype of quiescence, high proliferative potential and multipotency. We also characterized the cells at the molecular level using microarrays and identifi ed approximately 150 differentially expressed genes in these cells. Through genetic lineage analysis using an inducible K15-CrePR;R26R bigenic mouse, we showed that bulge cells generate all of the epithelial lineages within the lower anagen hair follicle. However, ablation of bulge cells using K15-thymidine kinase mice resulted in permanent hair loss but survival of the epidermis. Over a prolonged period, bulge cells did not contribute to epidermal homeostasis, but in response to wounding bulge cell progeny rapidly moved into the wound area to assist in reepithelialization. Bulge derived cells did not persist in the epidermis indicating that epidermal stem cells and hair follicle stem cells are distinct populations each with self renewing capabilities.

Page 41
Wnt-Dependent De Novo Hair Follicle
Regeneration in Adult Mouse Skin
Following Wounding
Ito, Mayumi; Yang, Zaixin; Andl, Thomas; Cui, Chunhua;
Kim, Noori; Millar, Sarah; Cotsarelis, George; Department of
Dermatology, University of Pennsylvania School of Medicine,
Philadelphia, PA, USA

The mammalian hair follicle is a complex “miniorgan” thought to form only during development; loss of an adult follicle is considered permanent. Here we show that, after wounding, hair follicles form de novo in genetically normal adult animals. The regenerated hair follicles establish a stem cell population, express known molecular markers of follicle differentiation, produce a hair shaft, and progress through all stages of the hair follicle cycle. Lineage analysis demonstrated that the nascent follicles arise from epithelial cells outside of the hair follicle stem cell niche, suggesting that epidermal cells surrounding the wound assume a hair follicle stem cell phenotype. Inhibition of Wnt signaling after reepithelialization completely abrogates this wounding induced folliculogenesis, while overexpression of Wnt ligand in the epidermis increases the number of regenerated hair follicles. These remarkable regenerative capabilitie of the adult support the notion that wounding induces an embryonic phenotype in skin, and that this provide a window for manipulation of hair follicle neogenesis by Wnts. These findings suggest novel treatments for wounds, hair loss and other degenerative skin disorders.

2

» I noticed this posted on another site
» http://www.nahrsmembers.org/home/Portals/0/meetings_support/abstracts_5th_congress/Final_Program_from_Bristol.pdf
»
»
» Lots of great speakers. For example
»
» Page 25
» Hair Follicle Stem Cells – Epithelial
» Speaker: George Cotsarelis, MD
» University of Pennsylvania, Philadelphia, PA, USA
» Over 15 years ago, we proposed that quiescent keratinocytes in the hair
» follicle bulge were epithelial stem cells important for hair follicle
» cycling, epidermal renewal, wound healing and carcinogenesis. Since that
» time, we identifi ed cytokeratin 15 (K15) expression as a marker for these
» cells and developed several transgenic mouse models using the K15 promoter
» to further study the bulge cells. Using K15-EGFP mice, we isolated bulge
» cells and demonstrated that they possessed an epithelial stem cell
» phenotype of quiescence, high proliferative potential and multipotency. We
» also characterized the cells at the molecular level using microarrays and
» identifi ed approximately 150 differentially expressed genes in these
» cells. Through genetic lineage analysis using an inducible K15-CrePR;R26R
» bigenic mouse, we showed that bulge cells generate all of the epithelial
» lineages within the lower anagen hair follicle. However, ablation of bulge
» cells using K15-thymidine kinase mice resulted in permanent hair loss but
» survival of the epidermis. Over a prolonged period, bulge cells did not
» contribute to epidermal homeostasis, but in response to wounding bulge cell
» progeny rapidly moved into the wound area to assist in reepithelialization.
» Bulge derived cells did not persist in the epidermis indicating that
» epidermal stem cells and hair follicle stem cells are distinct populations
» each with self renewing capabilities.
»
»
» Page 41
» Wnt-Dependent De Novo Hair Follicle
» Regeneration in Adult Mouse Skin
» Following Wounding
» Ito, Mayumi; Yang, Zaixin; Andl, Thomas; Cui, Chunhua;
» Kim, Noori; Millar, Sarah; Cotsarelis, George; Department of
» Dermatology, University of Pennsylvania School of Medicine,
» Philadelphia, PA, USA
»
» The mammalian hair follicle is a complex “miniorgan” thought to form only
» during development; loss of an adult follicle is considered permanent. Here
» we show that, after wounding, hair follicles form de novo in genetically
» normal adult animals. The regenerated hair follicles establish a stem cell
» population, express known molecular markers of follicle differentiation,
» produce a hair shaft, and progress through all stages of the hair follicle
» cycle. Lineage analysis demonstrated that the nascent follicles arise from
» epithelial cells outside of the hair follicle stem cell niche, suggesting
» that epidermal cells surrounding the wound assume a hair follicle stem cell
» phenotype. Inhibition of Wnt signaling after reepithelialization completely
» abrogates this wounding induced folliculogenesis, while overexpression of
» Wnt ligand in the epidermis increases the number of regenerated hair
» follicles. These remarkable regenerative capabilitie of the adult support
» the notion that wounding induces an embryonic phenotype in skin, and that
» this provide a window for manipulation of hair follicle neogenesis by Wnts.
» These findings suggest novel treatments for wounds, hair loss and other
» degenerative skin disorders.

so if its really just as simple as a wound producing new hair follicles, couldnt everyone here just take a needle and prick the top of their head a bunch of times?

3

so if its really just as simple as a wound producing new hair follicles, couldnt everyone here just take a needle and prick the top of their head a bunch of times?
I know people have tried… I also heard of results using a dermaroller, but it’s hard to believe anything in this industry without some decent before/after pics.

.

4

just quickly skimming through the document, I found some stuff from Dr Kemp

Page 113
Robotic Expansion of Cells for Use in Tissue
Engineering of Hair
Kemp, Paul D.; Intercytex, Manchester, UK
In order for hair multiplication by follicular cell implantation to be a practical proposition, the number of cells returned to the patient must be significantly greater than the number harvested. Moreover, for this process to be commercially successful and cover the high costs of cell culture, amanufacturing facility must have the capacity to expand the cells of many patients simultaneously. For safety reasons, each culture must be maintained in total isolation from the others to ensure that no cross-contamination can occur between the various patients’ cells. This has been a long standing issue with organisations involved in tissue engineering, especially those involved in autologous therapies. Three basic approaches have been employed to deal with the issues, and all three will be presented and their advantages and disadvantages discussed. Intercytex is following a strategy based on a robotic cell culture system that was previously developed and proven in the area of high throughput screening. This system uses standard tissue culture vessels and dispensers to feed and passage mammalian cells although they are net yet approved by regulators for use in tissue engineering. The adoption of a robotic system will impact research decisions made early in the development of a cell culture process so that the process will be made “robot friendly”. The system will be presented and the route to regulatory approval discussed.

Large Scale Manufacturing of Cell Therapy
For Hair Regeneration
Kemp, Paul D.; Intercytex, Manchester, UK
The implantation of follicular cells, expanded in culture, to induce potentially unlimited amounts of hair has been suggested ever since the work of Oliver and Jahoda. Companies are currently in Phase I and II studies to test preparations of cells for hair induction. It seems from the long history of research in this area that processes will soon be developed to successfully achieve this long sought after treatment. But how will these processes be translated into an industry whereby thousands or hundreds of thousands of people could be treated annually? Tissue Engineering is an industry now in its third decade and over a quarter of a million people have been treated by a variety of cultured cell constructs. The early pioneers developed processes often by trial and error, and only now is “best practise” beginning to emerge. The lessons learned in the past are crucial to the current development of tissue engineered hair and are the subject of this presentation. All tissue engineering processes can be broken down into six stages: “Tissue Procurement; “Cell Isolation”; “Cell Expansion”; “Assembly”; “Shipping”; and “Application”. Regulations, industry standards, and developments in other fields are rapidly evolving and influencing each of these stages. The talk will cover these six stages and describe how an industrial process could be developed to meet the commercial needs of large scale follicular cell implantation.

5

» so if its really just as simple as a wound producing new hair
» follicles, couldnt everyone here just take a needle and prick the top of
» their head a bunch of times?
» I know people have tried… I also heard of results using a dermaroller,
» but it’s hard to believe anything in this industry without some decent
» before/after pics.
»
»
»
»
» .

yes u are right how about some pics of your progress? :lol2:

6

» just quickly skimming through the document, I found some stuff from Dr
» Kemp
»
» Page 113
» Robotic Expansion of Cells for Use in Tissue
» Engineering of Hair
» Kemp, Paul D.; Intercytex, Manchester, UK
» In order for hair multiplication by follicular cell implantation to be a
» practical proposition, the number of cells returned to the patient must be
» significantly greater than the number harvested. Moreover, for this process
» to be commercially successful and cover the high costs of cell culture,
» amanufacturing facility must have the capacity to expand the cells of many
» patients simultaneously. For safety reasons, each culture must be
» maintained in total isolation from the others to ensure that no
» cross-contamination can occur between the various patients’ cells. This has
» been a long standing issue with organisations involved in tissue
» engineering, especially those involved in autologous therapies. Three basic
» approaches have been employed to deal with the issues, and all three will
» be presented and their advantages and disadvantages discussed. Intercytex
» is following a strategy based on a robotic cell culture system that was
» previously developed and proven in the area of high throughput screening.
» This system uses standard tissue culture vessels and dispensers to feed and
» passage mammalian cells although they are net yet approved by regulators
» for use in tissue engineering. The adoption of a robotic system will impact
» research decisions made early in the development of a cell culture process
» so that the process will be made “robot friendly”. The system will be
» presented and the route to regulatory approval discussed.
»
»
» Large Scale Manufacturing of Cell Therapy
» For Hair Regeneration
» Kemp, Paul D.; Intercytex, Manchester, UK
» The implantation of follicular cells, expanded in culture, to induce
» potentially unlimited amounts of hair has been suggested ever since the
» work of Oliver and Jahoda. Companies are currently in Phase I and II
» studies to test preparations of cells for hair induction. It seems from the
» long history of research in this area that processes will soon be developed
» to successfully achieve this long sought after treatment. But how will
» these processes be translated into an industry whereby thousands or
» hundreds of thousands of people could be treated annually? Tissue
» Engineering is an industry now in its third decade and over a quarter of a
» million people have been treated by a variety of cultured cell constructs.
» The early pioneers developed processes often by trial and error, and only
» now is “best practise” beginning to emerge. The lessons learned in the past
» are crucial to the current development of tissue engineered hair and are
» the subject of this presentation. All tissue engineering processes can be
» broken down into six stages: “Tissue Procurement; “Cell Isolation”; “Cell
» Expansion”; “Assembly”; “Shipping”; and “Application”. Regulations,
» industry standards, and developments in other fields are rapidly evolving
» and influencing each of these stages. The talk will cover these six stages
» and describe how an industrial process could be developed to meet the
» commercial needs of large scale follicular cell implantation.

excellent cut and paste

7

odd comment about growth/ direction issues (In bold)

Page 114
Proto-Hair Development In Vitro
Qiao, Jizeng; Turetsky, Anya; Teumer, Jeff; Intercytex, Woburn, MA, USA
Objectives: To develop an in vitro system in which to grow partially formed hair follicles that, when implanted, will continue to develop into fully formed hairs.

Approach: Hair follicle cells were prepared by enzymatic digestion followed by two sequential sievings. Cell aggregates were made and cultured to allow proto-hair development in vitro. Both freshly made and cultured aggregates were implanted onto an immune deficient mouse ear skin to test for mature hair development. Results: Aggregates made with freshly isolated cells consistently developed hairs after implantation. Aggregates cultured in vitro consistently developed proto-hairs, which are partially formed hair follicles with distinctive morphology. Such in vitro-produced proto-hairs further developed into mature hairs after implantation. Most implants developed hairs that grew out of the skin, while some developed underneath the skin surface but failed to emerge. Histological studies confirmed immature hair structures formed from cell aggregates during cultivation in vitro.

Conclusion:
• We demonstrated that proto-hairs can be produced in vitro from cultured cells.
• We proposed a concept of the immature ‘proto-hair’ as an option for clinical transplantation.

8

Looks like he’ll be talking about the “Surgical Management of Pattern Hair Loss” opposed to HM at the conference (Page 16/ WS-1-F)

9

» » I noticed this posted on another site
» »
»
» so if its really just as simple as a wound producing new hair follicles,
» couldnt everyone here just take a needle and prick the top of their head a
» bunch of times?

The wounding just creates that “window of opportunity” for epithelial cells to form into HF stem cells. As somebody stated before “this is not rocket science”, however the wounding, ie. depth and surface area covered may be a crucial component as well as the EGF that will be applied during this “window” to stimulate the wnt pathways. The EGF compound that will be used is the key don’t you think?

10

Conclusion:
• We demonstrated that proto-hairs can be produced in vitro from cultured cells.
• We proposed a concept of the immature ‘proto-hair’ as an option for clinical transplantation.

someone know if this proto hair are near the market of transplants? this colud be very great… imagine a work of hasson or alvi with 50.000 hairs

11

» so if its really just as simple as a wound producing new hair follicles,
» couldnt everyone here just take a needle and prick the top of their head a
» bunch of times?

The wounds have to be 2mm in diameter for the skin to heal in such a way as to produce a new hair follicle. In experiments, when wnt7a was introduced in the healing…about 13 times as many new follicles formed (the first patent has this graph on one of the last pages). Inhibiting epidermal growth factor during the healing time after skin re-epilithialization (about day 3 post wound to day five post wound in human skin depending on the severity of the wound) also increases the amount of hair that will be made.

There have been a few people who inject minoxidil with syringes, but the needle pricks would probably have to be pretty big to induce this kind of response. Whatever you do at home wont be nearly as good as what the professional researchers will be able to come up with and include in their “kits” to apply post dermabrasion. Its worked on human skin grafted onto a mouse…but in humans period is another matter. All we can really do is wait.

12

» Conclusion:
» • We demonstrated that proto-hairs can be produced in vitro from cultured
» cells.
» • We proposed a concept of the immature ‘proto-hair’ as an option for
» clinical transplantation.
»
»
» someone know if this proto hair are near the market of transplants? this
» colud be very great… imagine a work of hasson or alvi with 50.000 hairs

hell, this is what Ive been saying for years…grow the cells into hair OUTSIDE the scalp and re-implant as fully differentiated hair follicles. My idea years ago was to have hair removal done on the thighs…and implant cells for head hair in the thighs…any hair that grew could be FUE’d to the scalp as fully differentiated hairs. What didn’t grow didn’t grow. So what-no loss there. If we had a skin model that could subsist for a year or so we could plant hair seeds (cells) in it and try to induce at least proto-hairs for scalp implantion later. THis is good news that this is at least being tried. I really do think yield would be much much much better this way. MPB scalp has thinner skin, excessive collagen, water layer loss, less fatty acids, and probably is less vascularization than healthy donor-area scalp. There is a cytokine presence to existing vellus hairs in the throes of MPB also abundant there. Its not the best environment for new hairs to develop----so develop them somewhere else. We know fully diffentiated hairs do well whem moved there.

13

» » Conclusion:
» » • We demonstrated that proto-hairs can be produced in vitro from
» cultured
» » cells.
» » • We proposed a concept of the immature ‘proto-hair’ as an option for
» » clinical transplantation.
» »
» »
» » someone know if this proto hair are near the market of transplants?
» this
» » colud be very great… imagine a work of hasson or alvi with 50.000
» hairs
»
»
»
»
» hell, this is what Ive been saying for
» years…grow the cells into hair OUTSIDE the scalp and
» re-implant as fully differentiated hair follicles. My idea years ago was to
» have hair removal done on the thighs…and implant cells for head hair
» in the thighs…any hair that grew could be FUE’d to the
» scalp as fully differentiated hairs. What didn’t grow didn’t grow. So
» what-no loss there. If we had a skin model that could subsist for a year or
» so we could plant hair seeds (cells) in it and try to induce at least
» proto-hairs for scalp implantion later. THis is good news that this is at
» least being tried. I really do think yield would be much much much better
» this way. MPB scalp has thinner skin, excessive collagen, water layer loss,
» less fatty acids, and probably is less vascularization than healthy
» donor-area scalp. There is a cytokine presence to existing vellus hairs in
» the throes of MPB also abundant there. Its not the best environment for new
» hairs to develop----so develop them somewhere else. We know fully
» diffentiated hairs do well whem moved there.

if this is possible i take the first airplane tomorrow and i run to pay the society and after the surgeon for the transplant… only ICX is working on hair created in vitro? benji, you know others society? and especially… sureley the doctors know this technique? why don’t commercialize??

14

I have also thought of this for a very long time (although I don’t think I’d really want it grown in my thigh). But if they can grow proto-hairs outside the scalp and then transplant with FUE, and the yield is such that you could have virtually unlimited proto-hairs, then this would certainly be an acceptable solution for me.

The reason a HT is not acceptable to me now is that I can’t get a full head of hair back. Only an illusion. And also this would allow repair work much more easily, since you would always have more hair to transplant. That would be a nice fallback if I had a bad session. I guess we need to find out more on how reproducible this is and what the yield is. And then of course, when!