A Big Feat: Scientists Have Turned Skin Cells Into Limb Cells – Asian Scientist Magazine

AsianScientist (Mar. 27, 2024) – A new study has identified a mechanism that can turn skin cells into limb cells, opening possibilities for regenerative therapy. 

In a collaborative study, researchers from Kyushu University in Fukuoka, Japan, and Harvard Medical School, Boston, have identified proteins that can change fibroblasts, or skin cells into cells that behave like those found in developing limbs. This finding opens up possibilities for using these transformed cells in regenerative therapies, where damaged or lost tissues in limbs could potentially be repaired or replaced.

The research, published in the Developmental Cell journal, marks a significant stride towards understanding limb development and revolutionizing treatment for millions suffering from limb loss worldwide. Globally, close to 60 million people are living with limb loss, due to various medical conditions or traumatic incidents. People with limb injuries often rely on synthetic materials and metal prostheses, but despite technological advancements restoring natural limb functions remains a challenge. The new study sheds light on a potential treatment by reprogramming fibroblast cells into limb progenitor cells, that mirrors the natural process of limb development. 

Dr Yuji Atsuta, the lead researcher of the collaboration, says that their aim is to establish an accessible method for generating these crucial cells.

“During limb development in the embryo, limb progenitor cells in the limb bud give rise to most of the different limb tissues, such as bone, muscle, cartilage and tendon. It’s therefore important to establish an easy and accessible way of making these cells,” explains Atsuta, who started this project at Harvard Medical School and continues it as a lecturer at Kyushu University’s Graduate School of Sciences.

The breakthrough finding

Currently, a common way to obtain limb progenitor cells is directly from embryos, which, in the case of human embryos, raises ethical concerns. An alternate method involves creating these cells from induced pluripotent stem cells, which are adult cells transformed into a state similar to embryonic cells. Later, these reprogrammed cells can be coaxed to become specific types of tissues. However, induced pluripotent stem cells presented cancer risk. So Atsuta’s team devised a method bypassing induced pluripotent stem cells, directly transforming fibroblast cells into limb progenitors. This breakthrough not only simplifies the process but also mitigates cancer risks associated with induced pluripotent stem cells.

The research group initially scrutinized gene expression in early limb buds, identifying 18 crucial genes, predominantly the proteins called transcription factors. Transcription factors control gene expression in cells. Introducing these genes into mouse embryo fibroblasts spurred the cells to adopt limb progenitor properties.

Over a series of experiments, the team found three proteins—Prdm16, Zbtb16, and Lin28a—essential for fibroblast reprogramming. A fourth protein, Lin41, helped the cultured limb progenitor cells grow and multiply more rapidly.

“These reprogrammed cells are not only molecular mimics; we have confirmed their potential to develop into specialized limb tissues,” says Atsuta.

Atsuta’s lab group is now trying to apply this method to human cells, for future therapeutic applications, and also to snakes, whose ancestors had limbs that were subsequently lost during evolution. 

“The reprogrammed limb progenitor cells generated limb bud-like organoids, so it seems possible to generate limb tissues in species that no longer possess them. The study of limbless snakes can uncover new pathways and knowledge in developmental biology,” says Atsuta. 

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Source: Kyushu University ; Image: D. Burnette, J. Lippincott-Schwartz/NICHD

The article can be found at: Direct reprogramming of non-limb fibroblasts to cells with properties of limb progenitors

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