Reactivation of Hair Follicle Stem Cells Restarts Hair Growth


Sarah Millar and her team at the Perelman School of Medicine at the University of Pennsylvania have exploited a known property of hair follicle stem cells to restart hair growth in laboratory animals.

The Wnt signaling pathway is an important regulator of hair follicle proliferation, but does not seem to be required for hair follicle survival. Wnt signaling in cells culminated in the activation of a protein called beta-catenin, which goes to the nucleus of the cell and causes changes in gene expression.

wnt signaling

Millar and her colleagues disrupted Wnt signaling in laboratory animals by expressed an inhibitor called Dkk1 in hair follicles. Dkk1 expression prevented hair growth, and when the hair follicles were examined, they still had their stem cell populations, but these stem cells were dormant. Removal of Dkk1 resumed Wnt/beta-catenin signaling, and restored hair growth.

Dkk1 activity

Interestingly, Millar’s group found Wnt activity in non-hairy regions of the skin, such as palms, soles of feet, and so on. Therefore, in order for Wnt signaling to induce hair growth, it must occur within specific cell types.

This work also has additional applications: skin tumors often show over-active beta-catenin. Removing beta-catenin could prevent the growth of skin tumors, just as removing beta-catenin in the skin of these mice prevented proliferation of any hair follicles. However, agents that can activate beta-cateinin in hair follicles could reactivate dormant hair follicles and induce new hair growth.

Finding ways to safely reactivating the Wnt pathway in particular cells in the skin is a major focus of Millar’s research group.  Such work may lead to treatments for male pattern baldness.

Using Bone Marrow Stem Cells to Reprogram Neurons and Regenerate the Retina


Spanish researchers from the Center for Genomic Regulation (CGR) have regenerated the retina in mice by reprogramming neurons with bone marrow stem cells.

Cell reprogramming normally uses genetic engineering techniques that introduces genes into cells that push them into another cell fate without taking them through an embryonic-like state. One strategy for reprogramming cells fuses those cells with other cells that express genes that drive the fused cell into a different cell fate.

Pia Cosma and her team have used cell fusion to reprogram retinal neurons in mice. The mechanism consisted of introducing bone marrow stem cells into the damaged retina. The transplanted stem cells fused with existing retinal neurons, which conveyed to these retinal neurons the ability to regenerate the retina.

“For the first time we have managed to regenerate the retina and reprogram its neurons through in vivo cell fusion. We have identified a signaling pathway that, once activated, allows the neurons to be reprogrammed through their fusion with bone marrow cells,” said Pia Cosma, who is the head of the Reprogramming and Regeneration group at the CGR and ICREA (Institució Catalana de Recerca i Estudis Avançats) research professor.

Daniela Sanges, first author or the work and postdoctoral researcher in Pia Cosma’s laboratory, said, “This discovery is important not only because of the possible medical applications for retinal regeneration but also for the possible regeneration of other nervous tissues.”

The study demonstrates that the regeneration of nervous tissue by means of cell fusion is possible in mammals and describes this new technique as a potential mechanism for the regeneration of more complex nervous tissue.

This research is in the very early stages but already there are laboratories interested in being able to continue the work and take it to a more applied level.

Daniela Sanges, Neus Romo, Giacoma Simonte, Umberto Di Vicino, Ariadna Diaz Tahoces, Eduardo Fernández, Maria Pia Cosma. Wnt/β-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina . Cell Reports – 25 July 2013 (Vol. 4, Issue 2, pp. 271-286)

Alligator Stem Cells and Tooth Replacement


Mammals usually have one set of baby teeth (also known as milk teeth) and after those are lost, we have one set of adult teeth and these are not replaced if they are lost. This condition is called “monophyodont.” Reptiles and sharks, however constantly replace their teeth. This condition is called “polyphyodont.” Alligators and crocodiles are among one group of reptiles that replace their teeth throughout their lives, and because the development of these creatures has been studied to some extent, it is known that the ability of these creatures to replace their teeth on a regular basis results from a resident stem cell population. Studying that stem cell population more closely might provide clues for tooth replacement in humans.

American Alligator
American Alligator

A research team led by scientists at the Keck School of Medicine professor of pathology Cheng-Ming Chuong at the University of Southern California. Dr. Chuong and his collaborators from around the world have identified unique cellular and molecular mechanisms behind tooth renewals in American alligators.

Chuong explained, “Humans naturally have only two sets of teeth – baby teeth and adult teeth. Ultimately, we want to identify stem cells that can be used as a resource to stimulate tooth renewal in adult humans who have lost teeth. But, to do that, we must first understand how they renew in other animals and why they stop in people.”

Even though humans cannot replace their adult teeth, a tissue called the dental lamina remains, which is known to be crucial for tooth development.

Why are alligators potentially a good model system for tooth replacement in mammals? First author of this study, Ping Wu, explained it this way, “Alligator teeth are implanted in sockets of the dental bone, like human teeth. They have 80 teeth, each of which can be replaced up to 50 times over their lifetime, making them the ideal model for comparison to human teeth.”

Through the use of microscopic imaging techniques, Chuong and others found that each alligator tooth is a complex unit of three components: a functional tooth, a replacement tooth, and the dental lamina, all other which are at different developmental stages.

The tooth units are built to enable a smooth transition from dislodgement of the functional, mature tooth to replacement with a new tooth. Further imaging studies strongly suggested that the dental lamina contains a stem cell population from which new replacement teeth develop.

“Stem cells divide more slowly than other cells, said co-author Randall B. Widelitz, who serves as an associate professor of pathology at USC. Widelitz continued, “The cells in the alligator’s dental lamina behaved like we would expect stem cells to behave. In the future, we hope to isolate those cells from the dental lamina to see whether we can use them to regenerate teeth in the lab.”

The researchers also intend to learn what molecular networks are involved in repetitive renewal and hope to apply the principles to regenerative medicine in the future.

The authors also noted that novel cellular mechanisms are used during the development of the tooth unit. Also, unique molecular signaling speeds growth of replacement teeth when functional teeth are lost.

See P. Wu PNAS 2013; DOI: 10.1073/pnas.12132110.