Category Archives: 3D Spheroids

Biomimetic Hair Follicles, 3D Bioprinting, 3D Spheroids, Angela Christiano, Colin Jahoda

Tissue Engineering of Hair Follicles using a Biomimetic Approach

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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.”

Interleukin-1 (IL-1), 3D Spheroids, Krzysztof Kobielak, Malcolm XIng, Wounding

Wounding, Interleukin-1 and Other Hair News

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There were way too many developments in the past month, at least half of which probably deserved their own post.

Wounding, Interleukin-1 (IL-1) and γδ T-cells

Wounding induced hair growth has been in the news a lot over the past several years.

At the end of 2013, I first discussed Dr. Krzysztof Kobielak and Dr. Eve Kandyba from USC in relation to their work on how the Wnt7 gene activates hair growth. Fast forward to this month, and both scientists are back in the news and (via a collaboration with researchers from UC San Diego and from India) published an important paper titled: “Stimulation of hair follicle stem cell proliferation through an IL-1 dependent activation of γδT-cells“.

Interestingly, one of the three most important words used throughout the paper and of primary importance to us (“wounding” or “wound“) is missing from the above title, although not from the complementing photo (see red area in the image further below).

These scientists found that wounding triggers interleukin-1 (IL-1), which in turn activates certain immune cells (called γδT-cells or gamma delta cells). These immune cells then awaken resting stem cells in the hair follicle so that they can then “multiply and travel to the wound site to repair the injury”. For our purposes, the hair follicle stem cell activation is more important than any kind of wound repair (i.e., hair > scar improvement).

Commentator “Omg” who has posted some great material in recent weeks (including the above — thanks) wrote that this finding is the biggest discovery of the past decade. I am not so sure. Note that the authors of this latest work are not affiliated with Follica (the widely discussed company that is developing a “wounding + favorable compound injection” related procedure to regrow hair); nor are they affiliated with Dr. Rachita Dhurat, who has published several groundbreaking papers related to wounding and hair growth. Makes this discovery from an entirely different group all the more exciting, and further validates the potential of wounding spurred hair regrowth.

Wounding, Interleukin-1 and Hair Growth

Nanogel Encapsulated Dermal Papilla 3D Spheroids and Hair Follicle Regeneration

In 2015 I interviewed Dr. Malcolm Xing from Canada. In 2016, I discussed the same doctor’s new findings related to a novel improved “hanging drop” 3D cell culturing technique for the purpose of hair growth. Dr. Xing has constantly been trying to improve upon the renowned Dr. Colin Jahoda’s work.

This month, Dr. Xing and a team from China have published a new paper titled “Bottom-up Nanoencapsulation from Single Cells to Tunable and Scalable Cellular Spheroids for Hair Follicle Regeneration“.

I am not motivated enough to try to make the sci-hub site work to gain free access to this whole paper. I am, however, in no doubt that any new development related to 3D spheroids and hair culturing is of utmost importance and warrants coverage on this blog.

More Good News from Aclaris

In November, I discovered an interview in which Aclaris Therapeutics’ chief scientific officer mentioned that in the  first half of 2018, Aclaris planned to commence phase 2 trials to treat androgenetic alopecia (male pattern hair loss) with topical JAK inhibitors. This was a huge development, since we are used to virtually all companies in the hair loss world postponing or delaying clinical trials. In contrast, Aclaris is doing the opposite and moving to phase 2 trials without even having done phase 1 trials! They probably got to skip phase 1 trials because they have tested the same JAK inhibitors (including oral and topical versions) for other conditions.

Several weeks after I posted the above pleasing development, Aclaris announced at an investor conference that they would start the above trials at the end of the first quarter of next year (i.e, end of March 2018). Yet again they surprise us with their speed, and do not want to wait will June 2018. The announcement can be accessed by going to their website and finding their latest investor conference presentations (often available in both audio and slide formats).

Thanks to “Royaume” who listened to the whole audio for us (albeit misinterpreted its favorable implication). Commentator “Malcolm” even felt like I should have devoted a whole post to this news, but I did not want to do so less than a month after my prior post on Aclaris. Moreover, past experiences make me think that Aclaris will delay its trial commencement target dates (like all other companies seem to do), although I hope I am wrong.

Replicel CEO Update

Replicel’s CEO was interviewed by “Investing News” towards the end of last month. Key quote:

“There’s a possibility… that [our] hair products could have an early launch in Japan. Our partner Shiseido is funding a clinical trial in Japan that’s expected to release clinical data next year. It’s entirely up to Shiseido what they do in regards to this product. There’s certainly a possibility that they could decide if the data is positive, to launch the product in Japan and that would trigger… milestone payments and sales royalty revenue”.

Other Items of Interest

— I saw a number of comments and received several e-mails regarding the Brotzu lotion. It seems like they updated their EU patent page and several Italian hair loss forum members are claiming that the product is coming out in early 2018. For the time being I will refrain from writing a post on this, as it seems like there is a lot of speculation going on.

— A great thread with before and after photos on Reddit about the power of  the “Big 3” treatment of Finasteride plus Minoxidil plus Nizoral when effective.

— PolarityTE starts using its SkinTE product on humans. No info yet on potential hair growth effects on the scalp, but still great to see usage in humans rather than mice so early in the process. Key quote:

“We are confident and believe that SkinTE will replicate its preclinical success and help patients regenerate their own full-thickness, hair-bearing skin”.