New ‘recipe’ to build skin may help prevent scarring

By Stephen Beech via SWNS

A new "recipe" to build skin could help prevent scarring for future burns and stab victims, say scientists.

British researchers have for the first time created a single "cell atlas" of prenatal human skin to understand how skin forms, and what goes wrong in disease.

Researchers at the Wellcome Sanger Institute , Newcastle University , used single-cell sequencing and other state-of-the-art genomics techniques to create the atlas and uncover how human skin, including hair follicles, is formed.

They say their findings, published in the journal Nature , could be used to create new hair follicles in regenerative medicine and skin transplants for burn victims.

The team also created a "mini organ" of skin in a dish with the ability to grow hair.

Using the organoid, they showed how immune cells play a key role in scarless skin repair, which could lead to clinical applications to prevent scarring after surgery, or scarless healing after injuries such as a knife wound.

As part of the global Human Cell Atlas project, which is mapping all cell types in the human body, the researchers have provided a molecular "‘recipe" to build skin and a new organoid model to study congenital skin diseases.

Skin is the largest organ of the human body, providing a protective barrier, regulating our body temperature and it can even regenerate itself.

Scientists explained that skin develops in the sterile environment of the womb, with all hair follicles formed before birth – there is follicle cycling after birth, but no new follicles are made. Before birth, the skin has the unique ability to heal without scarring.

They say that understanding how skin develops, where cells are in space and time, and the role of genetics will help reveal how specific mutations cause congenital skin disorders, such as blistering and scaly skin.

In the new study, the Newcastle team created the first single-cell and spatial atlas of human prenatal skin.

They used samples of prenatal skin tissue, which they broke down to look at individual cells in suspension, as well as cells in place within the tissue.

Scientists used cutting-edge single-cell sequencing and spatial transcriptomics - a molecular method that maps gene activity in a tissue sample - to analyze individual cells in space and time, and the cellular changes that regulate skin and hair follicle development.

Using adult stem cells, the team also created a "mini organ" of skin in a dish, known as an organoid, with the ability to grow hair.

They compared the molecular characteristics of skin organoids with prenatal skin and found the skin organoid model more closely resembled prenatal skin than adult skin.

The researchers found that blood vessels didn't form in the skin organoid as well as prenatal skin.

By adding immune cells known as macrophages to the organoid, they discovered the macrophages promoted the formation of blood vessels, and the team undertook 3D imaging to assess blood vessel formation within the tissue.

It was known that the immune cells protect the skin from infection.

However, the study is the first time that macrophages have been shown to play a key role in the formation of human skin during early development by supporting the growth of blood vessels.

As a result of the study, the team has provided a molecular "recipe" for how human skin is built and how hair follicles form.

They say the insights could be used in the creation of new hair follicles for regenerative medicine, such as for skin transplants for burn victims, or those with scarring alopecia.

Study co-first author Dr. Elena Winheim, of the Wellcome Sanger Institute, said: “With our prenatal human skin atlas, we’ve provided the first molecular ‘recipe’ for making human skin and uncovered how human hair follicles are formed before birth.

"These insights have amazing clinical potential and could be used in regenerative medicine, when offering skin and hair transplants, such as for burn victims or those with scarring alopecia.”

Co-first author Dr. Hudaa Gopee, of Newcastle University, said: “We’re excited to have made a skin organoid model that grows hair.

"In this process, we uncovered a new, important role of immune cells in promoting the growth of blood vessels in developing skin tissue, which could help improve other organoid models.

"These immune cells, called macrophages, also appear to play a key part in scarless skin repair in prenatal skin.

"Our findings could inform clinical advances to avoid scarring after surgery.”

Co-lead author Professor Muzlifah Haniffa, interim head of cellular genetics at the Wellcome Sanger Institute, said: “Our prenatal human skin atlas and organoid model provide the research community with freely available tools to study congenital skin diseases and explore regenerative medicine possibilities."

She added: "We are making exciting strides towards creating the Human Cell Atlas, understanding the biological steps of how humans are built, and investigating what goes wrong in disease.”

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