Hair follicle tissues and cells for skin and hair replacement and stem cell research and discovery
Submitting InstitutionUniversity of Durham
Unit of AssessmentBiological Sciences
Summary Impact TypeHealth
Research Subject Area(s)
Biological Sciences: Biochemistry and Cell Biology, Genetics
Medical and Health Sciences: Oncology and Carcinogenesis
Summary of the impact
Fundamental research on developmental biology of skin and skin appendages
carried out by Prof Colin Jahoda's group has led to progress in the
isolation of specific adult cell populations, understanding of their roles
in skin and hair regeneration, and advances towards clinical applications.
This has led to the development of new methods to replace human hair
follicles, and has been the basis for multi-million dollar research and
development projects by companies in the UK, the US and Japan. The Durham
research has enabled Intercytex Ltd. to attract £27M in VC funding and
£30M in an IPO in 2009, progressing to Phase IIa clinical trials. The US
company Aderans Research Institute has spent $100 million in developing
this "hair cloning" technology. A Durham University spinout company,
ClarinnisBio, was also established in 2009, and has to date attracted ca.
£1M in investment and has employed two scientists, in a region of the UK
that suffers from relatively high levels of unemployment.
The underlying ideas for the hair replacement work, derived from findings
from animal models made by Dr Jahoda and his predecessors over many years,
that the hair follicle dermal cells were not only capable of participating
in and directing new hair follicle regeneration, but also had the capacity
to induce completely new follicles. A major advance came in 1999 when the
Jahoda group published a paper in Nature (ref. 1) demonstrating that human
hair follicle cells were also capable of inducing new follicles in human
skin (HAIR TRANSPLANTATION, PCT/GB2000/004177). This led to an upsurge of
interest in "hair cloning" with several commercial companies in particular
(including Intercytex in the UK and Aderans in the USA), investigating the
concept of multiplying follicle cells in culture and then grafting to
create an increased numbers of new hair follicles — so called "hair
cloning". In further research we showed that by manipulating cultured hair
follicle dermal cells to become three-dimensional spheroids that resemble
the native structures in the follicle, many key molecular signatures were
restored (ref. 2). This led to greater understanding of the molecular
expression underpinning human hair follicle induction, and we have shown
that it gives the cells greater potential to make new follicles when
grafted. This work is the subject of a joint patent application between
Durham and Columbia University, USA (20100303767 — METHODS FOR COMPACT
AGGREGATION OF DERMAL CELLS). As a follow on to this idea, with support
from the BBSRC, Prof. Jahoda has developed more complex double spheroid
organotypic structures in culture. These structures can be created from
skin or hair follicle cells, and have the capacity to be used as
proto-organs in grafting, either in isolation or as components of larger
skin equivalents. This work is the subject of another patent application
(WO/2013/014435 — MICRO ORGAN COMPRISING MESENCHYMAL AND EPITHELIAL
CELLS). Proof of principle that using cultured hair follicle dermal cells
to create 3 dimensional spheres makes it possible to induce entirely new
human hair follicles in human skin has been published in PNAS (ref. 3)
In relation to the skin model/skin replacement concept, it has long been
recognized that hair follicle epithelial stem cells make an important
contribution to skin wounding. Based on direct observations from animal
studies and scrutiny of the literature Jahoda proposed that follicle
dermal cells might play a parallel in the skin dermis, and published a
hypothesis paper outlining this idea (ref. 4). A worldwide patent was
granted based on the use of hair follicle dermal sheath cells in wound
healing (DERMAL SHEATH TISSUE IN WOUND HEALING, PCT/GB1998/001080).
One focus of the work has been to incorporate hair follicle dermal cells
into existing skin equivalent models with the aim of creating more
realistic and effective replacement dermal grafts (ref. 5). The other has
been the development of new simpler in vitro human skin models (ref. 6)
for research purposes and for and drug and molecular testing. A grant has
also been obtained during the REF period (from the charity DEBRA) to
provide preclinical evidence that the hair follicle dermal cells could be
used therapeutically for treating the blistering disease recessive
dystrophic epidermolysis bullosa (RDEB).
References to the research
. Reynolds, A.J., Lawrence, C., Cserhalmi-Friedman, P.B., Christiano,
A.M. and Jahoda C.A.B. (1999) Trans-gender induction of hair
follicles. Nature 402, 33-34.
2. Higgins CA, Richardson GD, Ferdinando D, Westgate GE, Jahoda CA.
(2010) Modelling the hair follicle dermal papilla using spheroid cell
cultures. Exp Dermatol. 19(6):546-48.
3. Higgins C.A., Chen J.C., Cerise J.E., Jahoda C.A.B.* and
Christiano A.M.* Microenvironmental reprogramming by three dimensional
culture enables dermal papilla cells to induce de novo human hair-follicle
growth. PNAS, e pub. October 2013. (*joint corresponding authors)
4. Jahoda, C.A.B. and Reynolds, A.J. (2001) Hair follicle dermal
sheath cells — unsung participants in wound healing. Lancet. 358,
5. Gharzi, A., Reynolds A.J. and Jahoda, C.A.B. (2003) Plasticity
of hair follicle dermal cells in wound healing and induction. Exp.
Dermatol. 12, 126-136.
6. Guo A, Jahoda CA (2009) An improved method of human
keratinocyte culture from skin explants: cell expansion is linked to
markers of activated progenitor cells. Exp Dermatol. 18(8):720-26.
BBSRC — January 2009, £98,693 Innovative methodologies developing the
commercialisation potential of human hair follicle induction.
MRC — October 2011, £454,037, Hair follicle induction by cultured human
BRITISH SKIN FOUNDATION — March 2007, £59,969, Hair follicle-derived
dermal stem cells.
DEBRA — June 2011, £134,743, Transplantation of Hair Follicle Dermal Cells
DTI (then TSB) — May 2006, £199,708, Process development and scale up of a
novel wound healing product using dermal stem cells
RegeNer8 — December 2010, £14,877, Isolation, characterization and scale
up culture of new dermal cell subpopulation for wound healing and cell
International interest in this research is supported by multiple
invitations to present plenary and keynote lectures at international
conferences, the most recent being a plenary lecture at the International
Hair Research Society meeting in Edinburgh in 2013, and the Norwood
lecture at the International Society of Hair Restoration Surgery's (ISHRS)
21st Annual Scientific Meeting in San Francisco, California, USA (October
Presented with the John Ebling Award for outstanding contribution to hair
Invited Professor, Université Joseph Fourier, Grenoble, France.
Winner of the BioNEt Award sponsored by Sanofi-Aventis. Professor Colin
Jahoda was awarded this new discretionary award for 2008 for his research
work at Durham University. The BioNET Award recognises excellence in
translational research and the pioneering work being carried out in both
the private and public sectors throughout the region. BioNEt is the North
East of England's leading network for research scientists and is the major
platform for sharing ideas and developments in the health, healthcare and
life sciences sector.
Details of the impact
From the hair induction work, the impact has come indirectly from
commercial enterprises taking forward the ideas established by the primary
research at Durham. In the UK this was exemplified by Intercytex, a
company founded in Manchester and relaunched in 2010. This company, listed
on the AIM, was the recipient of venture capital funding and a large TSB
grant for a robot to culture human hair follicle dermal cells. The Durham
research has enabled Intercytex Ltd. to attract £27M in VC funding and
£30M in an IPO in 2009. In the USA the company Bosley (now acquired by
Aderans) has spent ca. $100 million in developing this "hair cloning"
technology (Letter from the Chief Scientific Officer of Aderans Research
Institute, Inc.). Both of these companies initiated clinical trials of the
process during the REF period. Interestingly the US company has been using
a UK company Angel Biotechnology to grow their cells to GMP levels.
Numerous other companies and hair transplant clinics worldwide have
adopted or tried to adopt variations on the "hair cloning" technique (see
supporting letter from the founder of Intercytex).
One of the potential difficulties in using hair follicle cells in a
translational context is their relatively low numbers. This was addressed
in TSB-sponsored collaboration between Durham University, the NorthEast
regional agency CELS, and two industrial companies Avecia and Smith &
Nephew. In this project Avecia demonstrated the feasibility of scale-up
culturing of human hair follicle dermal cells to numbers sufficient for
translational use. The cell processing project carried out in association
with Avecia was instrumental/helpful in helping Avecia (now Fujifilm
Diosynth Biotechnologies) introduce mammalian cell culture work at their
facility, having previously worked exclusively on non-mammalian systems.
This includes the building of a new cGMP facility for manufacturing
mammalian products, the total investment at the mammalian site being $25M.
The company gained know-how and intellectual property (including patents)
that now supports their business strategy in this area. This has therefore
changed the way in which the company works, and consequently they have
improved their working practices (standard operating procedures) and
developed new products during the REF period (see supporting letter from
the Director of Science and Technology, Fujifilm Diaosynth
Recent impact is the creation of ClarinnisBio, a Durham University
spinout company. The Company was founded in 2009 by Dr Jahoda, and has
raised funding from the TSB, The Three Pillars fund and Regener8 to the
value of ca. £2 M. These funds have used to support research and
development work, with 2 staff being employed indirectly at Durham
University, contracted by the company. This supports the regional agenda
of creating and retaining jobs, particularly in new high technology
industries, in a region of the UK with relatively high levels of
unemployment. This incorporated patents on the use of hair follicle dermal
cells from prior work, and has established a new patent portfolio (MICRO
ORGAN COMPRISING MESENCHYMAL AND EPITHELIAL CELLS, PCT/GB2012/051759).
Sources to corroborate the impact
Letter from the founder of Intercytex providing testimony to the
importance of the research to the founding of the company.
Letter from the MD/Vice President of Research and Chief Scientific
Officer of Aderans Research Institute, Inc., who has 30 years of expertise
in hair follicle biology. He had a 20 year distinguished academic career
as a Professor of Pathology and Dermatology at the Yale University School
of Medicine and Dr. Stenn spent 10 years as Director of Skin Biology at
Johnson & Johnson. He served as a Scientific Advisory Board Member at
Follica, Inc. This letter describes the impact that the Jahoda lab
research has had on the R and D of skin and hair regeneration by the
Aderans company, and on the field in general.
Letter from the Director Science and Technology, Fujifilm Diosynth
Biotechnologies. This letter outlines the collaboration between the Jahoda
lab and the company for their standard operating procedures for stems
cells/cell therapy products and supporting the expansion of mammalian cell
culture R and D and cGMP facility at their Billingham site.
Preparation and publication of intellectual property (copies of
WO/2013/014435 — MICRO ORGAN COMPRISING MESENCHYMAL AND EPITHELIAL CELLS.
WO/2011/015862 — CELL SUPPORT COMPRISING DERMAL FIBROBLASTS
20100303767 — METHODS FOR COMPACT AGGREGATION OF DERMAL CELLS
WO/2001/032840 — HAIR TRANSPLANTATION — PCT/GB2000/004177
WO/1998/048860 — DERMAL SHEATH TISSUE IN WOUND HEALING PCT/GB1998/001080
Creation of a spin out Company:
Breadth of Interest:
Worldwide interest in "hair cloning" amongst the general public who see it
as a future means of treating hair loss — around 3,800,000 results from a
Google search on the internet, high profile publicity on BBC and Sky news
(October 21-23 2013). Numerous blogs, websites, discussion groups and
information from company publicity.