Vigorous Hair Growth from stem cells could treat baldness

USC researchers have grown hair follicles from skin cells reproduced in vitro in the lab.

Researchers outline a step-by-step sequence of events in the production of hair follicles from skin. Specifically, they were able to generate hair by uncovering the major molecular events necessary for the growth of skin and fostering it in adult shaved mice.

“Many aging individuals do not grow hair well, because adult cells lose their regenerative ability. But with our new findings, we are able to make adult mouse cells produce hair again,” says Dr. Chuong.

Researchers at the USC lab could not confirm exactly when human trials could begin but were optimistic their findings could inspire a method for treating humans with alopecia and baldness in the near future by using some of the patient’s own stem cells to grow skin with hair follicles in a lab, then transplanting it onto balding areas of the scalp.

* they used progenitor cells, a cell type more differentiated from stem cells.
* They transplanted the cells into shaved mice
* the cells formed skinlike “organoids,” 3-D assemblies of cells that gathered themselves into an organlike structure, which in this case was the ability to grow hair. Further, they took hundreds of time-lapse movies to analyze the collective cell behavior.
* the cells combined themselves into polarized cysts, which then coalesced to form layered skin
* they created skin with hair follicles that were transplanted onto the back of a host mouse. Finally, they observed as the follicles vigorously produced hair.

There are between 100,000 to 150,000 hairs on human beings’ heads. Of these, 40 to 100 hairs are lost each day, which are replaced by new ones grown from the hair follicles.

PNAS – self-organization process in newborn skin organoid formation inspires strategy to restore hair regeneration of adult cells

Significance

This study opens avenues to improve the ability of adult skin cells to form a fully functional skin, with clinical applications. Our investigation elucidates a relay of molecular events and biophysical processes at the core of the self-organization process during tissue morphogenesis. Molecules key to the multistage morphological transition are identified and can be added or inhibited to restore the stalled process in adult cells. The principles uncovered here are likely to function in other organ systems and will inspire us to view organoid morphogenesis, embryogenesis, and regeneration differently. The application of these findings will enable rescue of robust hair formation in adult skin cells, thus eventually helping patients in the context of regenerative medicine.

Abstract
Organoids made from dissociated progenitor cells undergo tissue-like organization. This in vitro self-organization process is not identical to embryonic organ formation, but it achieves a similar phenotype in vivo. This implies genetic codes do not specify morphology directly; instead, complex tissue architectures may be achieved through several intermediate layers of cross talk between genetic information and biophysical processes. Here we use newborn and adult skin organoids for analyses. Dissociated cells from newborn mouse skin form hair primordia-bearing organoids that grow hairs robustly in vivo after transplantation to nude mice. Detailed time-lapse imaging of 3D cultures revealed unexpected morphological transitions between six distinct phases: dissociated cells, cell aggregates, polarized cysts, cyst coalescence, planar skin, and hair-bearing skin. Transcriptome profiling reveals the sequential expression of adhesion molecules, growth factors, Wnts, and matrix metalloproteinases (MMPs). Functional perturbations at different times discern their roles in regulating the switch from one phase to another. In contrast, adult cells form small aggregates, but then development stalls in vitro. Comparative transcriptome analyses suggest suppressing epidermal differentiation in adult cells is critical. These results inspire a strategy that can restore morphological transitions and rescue the hair-forming ability of adult organoids: (i) continuous PKC inhibition and (ii) timely supply of growth factors (IGF, VEGF), Wnts, and MMPs. This comprehensive study demonstrates that alternating molecular events and physical processes are in action during organoid morphogenesis and that the self-organizing processes can be restored via environmental reprogramming. This tissue-level phase transition could drive self-organization behavior in organoid morphogenies beyond the skin.

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