CATALYST FOR HAIR FOLLICLE BIOLOGY (CHFB) - Established in December 2002, this two-year collaboration totals $230,000 in funding, and brings together two leading hair follicle biologists. The Foundation announced the researchers and the consortium in January. The members are:
This consortium funding offers the potential to build upon the results that Dr. Christiano and Dr. Colin Jahoda have achieved through their informal collaboration thus far. As a result of publicity about Dr. Jahoda's work, there have been a number of lucrative offers to market human hair loss "cures" from commercial sources. Both Drs. Jahoda and Christiano, however, believe that developing the research for therapeutic purposes should be done on an independent scientific basis. Unfortunately, given that conventional avenues of research funding consider this to be a 'cosmetic' problem, few, if any funds are available. We hope that by encouraging and supporting an effective collaboration, we will add real value to the work being conducted in these laboratories and send a positive message that can be leveraged into funding from other sources.
- Angela M. Christiano, PhD (Columbia University, New York)
"We are very grateful to the Kirsch Foundation for its support of hair research. It is not often that scientists in our field have the privilege of being sponsored by such a prestigious organization. We are now in a unique position to make great strides in our work, as a direct result of this commitment."
- Colin A. B. Jahoda, PhD (Durham University, England)
"This is an outstanding opportunity to tackle a human condition that is of widespread concern for individuals and poses genuinely interesting scientific challenges. The Foundation has helped to fill a void in funding that will allow us to bring a direct and unfettered approach to the research. The collaborative element is crucial in bringing together distinctive but complementary skills and technologies, as well as beneficial individual interactions. This has to be a good way of doing science."
Left to right: Angela M. Christiano, PhD, and Colin A. B. Jahoda, PhD
The CHFB consortium will apply the emerging technologies of developmental biology, stem cell biology and tissue engineering to the induction of new hair follicles. The investigators have pioneered methods for the culture of hair follicle cells, and Dr. Jahoda was the first individual to demonstrate that new hair follicles can be induced to form in adult skin by implantation of cultured cells. Up to now, work has mainly been performed in animal models, and the induction of human hair follicles poses specific challenges relating to human hair follicle biology. The major focus of the CHFB is to establish that new human hair follicles can be created from cultured cells in adult human skin using transplantation techniques. The overall goal is the unequivocal demonstration that cultured human cells can induce new follicle formation and hair growth in human skin. Ultimately the hope is that the research can be used successfully to cure such conditions as premature balding and alopecia areata and offer solutions for hair loss due to chemotherapy.
The three primary strategies for the two-year research period include:
- Using a combination of in vitro and in vivo techniques, determine the conditions required for induction of new hair follicles.
Rationale: Adult hair follicles do not grow and produce hair continuously but periodically undergo phases of regression and quiescence before restarting a new growing phase. Collectively this process is termed the follicle growth cycle, and to maintain and control this complex series of events requires that the principal cell types in the follicle retain powerful interactive signaling properties. We have used microdissection techniques to isolate dermal cells from the base of rodent follicles and shown that small aggregates of these cells (freshly isolated or cultured) will induce new hair follicles when combined with epidermis. We can now use this “cell therapy” approach with the equivalent human cell populations. By removing the cells from follicles, multiplying them in culture, and transplanting them back into skin, we should be able to induce multiple new follicles from a few original donors.
- Determine the gene expression profile of microdissected populations of hair follicle cells.
Rationale: While it is generally believed that the control of hair follicle morphogenesis and cycling is genetically determined, the precise nature of the hair follicle-specific genes involved has remained elusive. There are many examples of genes involved in the ubiquitous developmental pathways being present in the hair follicle, including Wnts, BMPs, Shh, TGFß and others, and their role in the hair follicle has been largely derived from the functions in other tissues, such as the developing limb. While these genes are clearly important in hair follicle morphogenesis and cycling, their rather widespread usage in many developmental programs suggests that they cannot be the only genes involved in governance of hair follicle induction or in the hair cycle. In recent years, using a combination of molecular and comparative genomic approaches, we have identified several genes whose expression is largely restricted to the hair follicle, and thus have proven to have a highly specific function in hair growth. In this study, we will initiate a search for novel genes whose expression and function is restricted to discrete cell populations within the hair follicles.
- Establish a method to improve and standardize the in vivo propagation of new hair follicles.
Rationale: One of the challenges of in vivo hair follicle induction has revolved around the proper orientation and positioning of the inductive mesenchyme relative to the overlying epithelium. Previous work in our lab has demonstrated that the mesenchyme must be in close proximity to the epithelium for successful hair follicle induction. Furthermore, we have noticed in our previous work that one property of inductive DS or DP cells is their capacity for migration out of the site of implantation. Loss of DP or DS cells from the implantation site is a major obstacle in developing this technology and migration of dermal cells away from the epithelium will result in lack of induction.
Serving as an advisor to the consortium is Dr. Cheng-Ming Chuong, Professor of Pathology at the University of Southern California.
"Hair is the only place in the body that continues to shed and regenerate. It has a large pool of stem cells that maintains throughout our lives. It is like the fountain of youth. We need to learn how to use it. Drs. Jahoda and Christiano make up the dream team in hair biology research. Interesting new findings will emerge from this collaboration. I am thrilled that the Kirsch Foundation can support this endeavor. I am excited to see what will come out."
Year One Progress Report
Our previous work has demonstrated that the key dermal cells from the base of the hair follicle, the dermal papilla cells are key to the creation of hair follicles and to control of hair growth in mature follicles. Another related group of cells, the dermal sheath, are an important reservoir for replacing papilla cells that are lost.
In this period we have published the first description in which both of these cell types have been "cloned". This cloning, which is not to be confused with the much publicized reproductive cloning, involves isolating single cells and then growing up large populations from these lone progenitors. This is a key step in possible therapeutic developments since it potentially allows us to select specific cell populations that are able to stimulate hair follicles to form. To this end we have been analyzing the cellular and molecular properties of different clonal lines as a prelude to testing their functional capabilities. Intriguingly, we have also discovered that some papilla and sheath cells are adult stem cells in that they can be turned into other tissues such as bone and fat. Therefore the scope for practical use of such cells goes beyond skin and hair.
Year Two Progress Report
CHFB is a partnership aimed at applying the emerging technologies of developmental biology, stem cell biology and tissue engineering to the induction of new hair follicles. CHFB investigators have pioneered methods for the culture of hair follicle cells, and were the first to demonstrate that new hair follicles can be induced to form in adult skin by implantation of cultured cells. Up to now, work has mainly been performed in animal models, and the induction of human hair follicles poses specific challenges relating to human hair follicle biology. As a prelude to human clinical trials, the major focus of the CHFB is to establish that new human hair follicles can be created from cultured cells in adult human skin using transplantation techniques. Our overall goal is the unequivocal demonstration that cultured human cells can induce new follicle formation and hair growth in human skin. In this context we have also explored the relationship between hair follicles and other appendages and to this end we have demonstrated that tooth derived cells can induce new fiber growth in hair follicles.
We performed a microarray comparison between freshly dissected DP cells from rat vibrissa compared to freshly dissected DS cells from the same animals. This highly informative microarray study has yielded much information that will provide a foundation for the analysis of induction-promoting genes. We expanded this microarray approach and have performed microdissection on several other hair follicle compartments, including germinative epithelial cells, hair matrix cells, and bulge region cells. Additionally, we have performed a detailed time-course study of microdissected dermis and epidermis during mouse embryonic development on the back skin as well as the whisker pad. This approach has been enormously fruitful and has revealed several interesting novel candidate genes involved in hair follicle induction.
At the conclusion of this period of two years, the CHFB has allowed us to make significant advances toward the goal of propagation of hair follicle cells in culture and induction of new hair follicles using human cells. It is anticipated that this technology could represent a novel methodology for cell-based and tissue engineering approaches to the regeneration of new hair follicles.
Publications Resulting from the CHFB Project
CA Jahoda, CJ Whitehouse, AJ Reynolds, & N Hole. 2003. Hair follicle dermal cells differentiate into adipogenic and osteogenic lineages. Exp. Dermatol. 12:849-849.
AM Christiano. 2004. Epithelial stem cells: stepping out of their niche. Cell. 118:530-532.
AM Christiano and CA Jahoda. 2004. Special issue on epidermal and hair follicle differentiation, part 1. Differentiation. 72:363.
AM Christiano and CA Jahoda. 2004. Special issue on epidermal and hair follicle differentiation, part 2. Differentiation. 72:465.
I Fliniaux, JP Viallet, D Dhouailly, & CA Jahoda. 2004. Transformation of amnion epithelium into skin and hair follicles. Differentiation. 72:558-565.
CA Jahoda, A Kljuic, R O’Shaughnessy, N Crossley, CJ Whitehouse, M Robinson, AJ Reynolds, M Demarchez, RM Porter, L Shapiro, & AM Christiano. 2004. The lanceolate hair rat phenotype results from a missense mutation in a calcium-coordinating site of the desmoglein 4 gene. Genomics. 83:747-756.
H Kim, AA Panteleyev, CA Jahoda, Y Ishii, & AM Christiano. 2004. Genomic organization and analysis of the hairless gene in four hypotrichotic rat strains. Mamm Genome. 15:975-981.
RF O’Shaughnessy and AM Christiano. 2004. Inherited disorders of the skin in human and mouse: from development to differentiation. Int J Dev Biol. 48:171-179.
RF O’Shaughnessy, AM Christiano, & CA Jahoda. 2004. The role of BMP signaling in the control of ID3 expression in the hair follicle. Exp Dermatol. 13(10):621-9.
RF O’Shaughnessy, W Yeo, J Gautier, CA Jahoda, & AM Christiano. 2004. The WNT signaling modulator, Wise, is expressed in an interaction-dependent manner during hair follicle cycling. J Invest Dermatol. 123(4):613-21.
AJ Reynolds and CA Jahoda. 2004. Cultured human and rat tooth papilla cells induce hair follicle regeneration and fiber growth. Differentiation. 72:566-575.
H Uyttendaele, AA Panteleyev, D de Berker, DT Tobin, & AM Christiano. 2004. Activation of Notch 1 in the hair follicle leads to cell-fate switch and Mohawk alopecia. Differentiation. 72:396-409.
GD Richardson, EC Arnott, CJ Whitehouse, C Lawrence, AJ Reynolds, N Hole, & CAB Jahoda. In press. Plasticity of rodent and human hair follicle dermal cells- Implications for cell therapy and tissue engineering. Dermatol.
GD Richardson, EC Arnott, CJ Whitehouse, CM Lawrence, N Hole, & CAB Jahoda. In press. Cultured cells from adult human hair follicle dermis can be directed towards adipogenic and osteogenic differentiation. Dermatol.
E. Arnott, G Richardson, CJ Whitehouse, AM Christiano, & CAB Jahoda. Submitted. Human hair follicle dermal papilla cells differentiate into adipogenic and osteogenic lineages. J Invest Dermatol.