Category Archives: Angela Christiano

Tissue Engineering of Hair Follicles using a Biomimetic Approach

In 2004, Aderans Research Institute filed a patent (granted in 2009) titled “Tissue engineered biomimetic hair follicle graft“. The invention entailed an improved scaffold that would mimic the architecture of the native hair follicle. The ultimate aim for this invention after further improvements would be hair multiplication. However, for a number of reasons, the much hyped Aderans liquidated its research institute in 2013.

In the above patent filing, the most cited author when it comes to reference material was Durham University (UK)’s Dr. Colin Jahoda. To be specific, 10 of his past papers are cited: ranging from this one from 1981 to a 2001 paper on trans-species hair growth induction. The industrious Dr. Jahoda has published numerous other major research papers since 2001, some of which I have covered on this blog in the past.

Biomimetic Engineering of Human Hair

Biomimetic Tissue Engineering of Hair
Biomimetic engineered human hair growing on a mouse.

Several days ago, a groundbreaking new research paper was published in Nature Communications. The title of this paper was: “Tissue engineering of human hair follicles using a biomimetic developmental approach”. Very similar to the title of the earlier mentioned patent.

Moreover, one of the main co-authors of this latest 2018 work is Durham University’s Dr. Colin Jahoda. The other authors are all researchers from US-based Columbia University’s Department of Dermatology, led by the renowned Dr. Angela Christiano.

The conclusion of this research is one that should make everyone enthused:

“The ability to regenerate an entire hair follicle from cultured human cells will have a transformative impact on the medical management of different types of alopecia, as well as chronic wounds, which represent major unmet medical needs.”

Note that this latest paper was submitted in May 2018, accepted in October 2018, and finally published in December 2018. So the Jahoda, Christiano et al. team’s current research is at least seven months ahead of what is described in the paper.

3D-Spheroid Cultures to 3D-Printed Molds

I have covered 3D-spheroids, 3D-culturing and related structures and scaffolds (to help brand new hair follicles grow from scratch) numerous times. This area of research has seemed to be the holy grail for scientists trying to succeed at hair multiplication. Just like DHT elimination and restarting Wnt/β-catenin signaling have been the holy grails when it comes to preventing further hair loss and regrowing existing miniaturized hair.

Numerous scientists such as Dr. Colin Jahoda and Dr. Takashi Tsuji have focused on research 3D-spheroids and 3D-culturing of dermal papilla cells to grow new hair follicles for many years. However, in this latest study, it seems like the scientists have turned there focus to 3D-printing (or 3D-bioprinting). They even give the name of the specific 3D printer that they used during this experimentation.

The Jahoda, Christiano et. al team created 3D-printed hair follicle molds as the key component of the experiment. The scientists used a biomimetic approach to generate human hair follicles within human skin constructs (HSCs). They emulated human biology via the 3D organization of cells in the hair follicle micro-environment using 3D-printed molds. The actual paper is very technical.

The authors suggest that in the future, 3D bioprinting technology operating at a single cell resolution may permit the inclusion of many other cell types. This would include stem cells and melanocytes, which would generate hair cycling and pigmented hair follicles.

Some interesting quotes from the paper:

“We recently addressed this issue by 3D-spheroid culture of cells and thereby restored 22% of the hair inductive DPC gene signature. Subsequently, other groups also reported the use of this method to induce HFs in mice, albeit inefficiently. To enhance the efficiency of hair induction properties, in this study, we combined genetic and microenvironmental reprogramming strategies by overexpressing the MR gene Lef-1 in combination with spontaneous DPC spheroid formation in the HSCs, which resulted in 70% success rate of HF formation ex vivo, compared to only 19% with the empty vector-transfected DPCs.”

“Using 3D-printing approaches, our goal is to engineer HFs as follicular units and/or in desired patterns that can be integrated with surgical robots and facilitate effective hair transplantation surgery.”

JAK-STAT Signaling Jump Starts the Hair Cycle

JAK-STAT Signaling
JAK-STAT signaling hair growth mechanism of action.

Over the past few years, I have discussed the janus kinase signal transducer and activator of transcription (JAK-STAT) signaling pathway a number of times. It has become of increasing importance in the hair loss world ever since JAK inhibitors were first shown to cure alopecia areata (AA) in 2014. Even prior to that development, there had always been some interest in the JAK-STAT signaling pathway and its relationship to the hair follicle cycle.

JAK-STAT Signaling Jump Starts the Hair Cycle

However, since 2014, research in this area seems to have multiplied significantly. In 2015, I discussed Dr. Angela Christiano, Dr. Claire Higgins et al’s groundbreaking paper titled “Pharmacologic inhibition of JAK-STAT signaling promotes hair growth”.

Now, in the latest (November 2016) issue of Journal of Investigative Dermatology, Columbia University’s Dr. Angela Christiano, Dr. Etienne Wang and Dr. Sivan Harel have published a new paper titled “JAK-STAT signaling jump starts the hair cycle“.

However, it should be noted that this paper does not pertain to any new study or research by Dr. Christiano. Instead, it is largely an analysis by the Columbia University team of a study/paper that was published earlier this year by Dr. Julien Legrand and his team at The University of Queensland.

This study from Australia was titled “STAT5 activation in the dermal papilla Is important for hair follicle growth phase Induction“. The conclusion of that paper was that “STAT5 activation acts as a mesenchymal switch to trigger natural anagen entry in postdevelopmental hair follicle cycling“. STAT5 is an acronym for signal transducer and activator of transcription 5.

Dr. Christiano’s team raises some interesting points in their analysis. Especially the fact that while Dr. Legrand’s research has shown that JAK/STAT5 signaling in the dermal papilla is required for anagen onset in the murine (mice) hair cycle, other researchers have shown that JAK inhibition is able to induce the transition of telogen to anagen in wild-type mice. This contradiction highlights the complexity and still yet to be fully understood nature of JAK-STAT signaling in the various stem cell niches of the hair follicle.

Dr. Christiano continues to believe that topical JAK inhibitors could work to treat regular male pattern hair loss. She thinks that targeting the JAK-STAT pathway could be a potential treatment for non-immune alopecias.

“Further work in this exciting area may uncover novel pathways that control hair follicle stem cell quiescence and activation. Targeting these pathways pharmacologically may facilitate the discovery of new therapies to treat various forms of alopecia”.

“In our recent study we found that in wild-type mice, topical application (rather than systemic treatment) with JAK inhibitors was required to trigger the telogen-to-anagen transition.”

This could possibky be due to a requirement for a high threshold level of local concentration of the drug in the hair follicle. The Columbia team also found that the timing of topical treatment was crucial. The treatment induced hair growth only if administered after 8.5 weeks (during late telogen phase).

Nothing groundbreaking in this development, but it seems like the University of Queensland based Australian team of researchers is important enough to warrant inclusion in my global map of hair loss research centers. One of the co-authors (Dr. Kiarash Khosrotehrani) of their paper specifically mentions research interest in “hair follicle biology, cycling and regeneration” in his biography page.