Generation of iPSC-derived limb progenitor-like cells for stimulating phalange regeneration in the adult mouse

Ying Chen; Hanqian Xu; Gufa Lin

doi:10.1038/celldisc.2017.46

Generation of iPSC-derived limb progenitor-like cells for stimulating phalange regeneration in the adult mouse

Ying Chen, Hanqian Xu, Gufa Lin

Stem Cell Institute

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

The capacity of digit tip regeneration observed both in rodents and humans establishes a foundation for promoting robust regeneration in mammals. However, stimulating regeneration at more proximal levels, such as the middle phalanges (P2) of the adult mouse, remains challenging. Having shown the effectiveness of transplantation of limb progenitor cells in stimulating limb regeneration in Xenopus, we are now applying the cell transplantation approach to the adult mouse. Here we report that both embryonic and induced pluripotent stem cell (iPSC)-derived limb progenitor-like cells can promote adult mouse P2 regeneration. We have established a simple and efficient protocol for deriving limb progenitor-like cells from mouse iPSCs. iPSCs are cultured as three-dimensional fibrin bodies, followed by treatment with combinations of Fgf8, CHIR99021, Purmorphamine and SB43542 during differentiation. These iPSC-derived limb progenitor-like cells resemble embryonic limb mesenchyme cells in their expression of limb-related genes. After transplantation, the limb progenitor-like cells can promote adult mouse P2 regeneration, as embryonic limb bud cells do. Our results provide a basis for further developing progenitor cell-based approaches for improving regeneration in the adult mouse limbs.

Original language	English (US)
Article number	17046
Journal	Cell Discovery
Volume	3
DOIs	https://doi.org/10.1038/celldisc.2017.46
State	Published - Dec 19 2017

Bibliographical note

Funding Information:
The authors thank Dr Jonathan Slack for scientific input in this project and critical reading of the manuscript. We are grateful to Drs Jakub Tolar, Atsushi Asakura and James Dutton for discussions. The authors' research was supported by grants from the NICHD, NIH (R21HD076864, R01HD084440), National Science Foundation of China (31571491), Science and Technology Commission of Shanghai Municipality (15PJ1407200) and the Medical School/UMF of the University of Minnesota.

Funding Information:
The authors thank Dr Jonathan Slack for scientific input in this project and critical reading of the manuscript. We are grateful to Drs Jakub Tolar, Atsushi Asakura and James Dutton for discussions. The authors’ research was supported by grants from the NICHD, NIH (R21HD076864, R01HD084440), National Science Foundation of China (31571491), Science and Technology Commission of Shanghai Municipality (15PJ1407200) and the Medical School/UMF of the University of Minnesota.

Publisher Copyright:
© The Author(s) 2017.

Keywords

adult
fibrin body
limb progenitor cells
phalange regeneration
transplantation

Publisher link

10.1038/celldisc.2017.46

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735367

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title = "Generation of iPSC-derived limb progenitor-like cells for stimulating phalange regeneration in the adult mouse",

abstract = "The capacity of digit tip regeneration observed both in rodents and humans establishes a foundation for promoting robust regeneration in mammals. However, stimulating regeneration at more proximal levels, such as the middle phalanges (P2) of the adult mouse, remains challenging. Having shown the effectiveness of transplantation of limb progenitor cells in stimulating limb regeneration in Xenopus, we are now applying the cell transplantation approach to the adult mouse. Here we report that both embryonic and induced pluripotent stem cell (iPSC)-derived limb progenitor-like cells can promote adult mouse P2 regeneration. We have established a simple and efficient protocol for deriving limb progenitor-like cells from mouse iPSCs. iPSCs are cultured as three-dimensional fibrin bodies, followed by treatment with combinations of Fgf8, CHIR99021, Purmorphamine and SB43542 during differentiation. These iPSC-derived limb progenitor-like cells resemble embryonic limb mesenchyme cells in their expression of limb-related genes. After transplantation, the limb progenitor-like cells can promote adult mouse P2 regeneration, as embryonic limb bud cells do. Our results provide a basis for further developing progenitor cell-based approaches for improving regeneration in the adult mouse limbs.",

keywords = "adult, fibrin body, limb progenitor cells, phalange regeneration, transplantation",

author = "Ying Chen and Hanqian Xu and Gufa Lin",

note = "Funding Information: The authors thank Dr Jonathan Slack for scientific input in this project and critical reading of the manuscript. We are grateful to Drs Jakub Tolar, Atsushi Asakura and James Dutton for discussions. The authors' research was supported by grants from the NICHD, NIH (R21HD076864, R01HD084440), National Science Foundation of China (31571491), Science and Technology Commission of Shanghai Municipality (15PJ1407200) and the Medical School/UMF of the University of Minnesota. Funding Information: The authors thank Dr Jonathan Slack for scientific input in this project and critical reading of the manuscript. We are grateful to Drs Jakub Tolar, Atsushi Asakura and James Dutton for discussions. The authors{\textquoteright} research was supported by grants from the NICHD, NIH (R21HD076864, R01HD084440), National Science Foundation of China (31571491), Science and Technology Commission of Shanghai Municipality (15PJ1407200) and the Medical School/UMF of the University of Minnesota. Publisher Copyright: {\textcopyright} The Author(s) 2017.",

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N2 - The capacity of digit tip regeneration observed both in rodents and humans establishes a foundation for promoting robust regeneration in mammals. However, stimulating regeneration at more proximal levels, such as the middle phalanges (P2) of the adult mouse, remains challenging. Having shown the effectiveness of transplantation of limb progenitor cells in stimulating limb regeneration in Xenopus, we are now applying the cell transplantation approach to the adult mouse. Here we report that both embryonic and induced pluripotent stem cell (iPSC)-derived limb progenitor-like cells can promote adult mouse P2 regeneration. We have established a simple and efficient protocol for deriving limb progenitor-like cells from mouse iPSCs. iPSCs are cultured as three-dimensional fibrin bodies, followed by treatment with combinations of Fgf8, CHIR99021, Purmorphamine and SB43542 during differentiation. These iPSC-derived limb progenitor-like cells resemble embryonic limb mesenchyme cells in their expression of limb-related genes. After transplantation, the limb progenitor-like cells can promote adult mouse P2 regeneration, as embryonic limb bud cells do. Our results provide a basis for further developing progenitor cell-based approaches for improving regeneration in the adult mouse limbs.

AB - The capacity of digit tip regeneration observed both in rodents and humans establishes a foundation for promoting robust regeneration in mammals. However, stimulating regeneration at more proximal levels, such as the middle phalanges (P2) of the adult mouse, remains challenging. Having shown the effectiveness of transplantation of limb progenitor cells in stimulating limb regeneration in Xenopus, we are now applying the cell transplantation approach to the adult mouse. Here we report that both embryonic and induced pluripotent stem cell (iPSC)-derived limb progenitor-like cells can promote adult mouse P2 regeneration. We have established a simple and efficient protocol for deriving limb progenitor-like cells from mouse iPSCs. iPSCs are cultured as three-dimensional fibrin bodies, followed by treatment with combinations of Fgf8, CHIR99021, Purmorphamine and SB43542 during differentiation. These iPSC-derived limb progenitor-like cells resemble embryonic limb mesenchyme cells in their expression of limb-related genes. After transplantation, the limb progenitor-like cells can promote adult mouse P2 regeneration, as embryonic limb bud cells do. Our results provide a basis for further developing progenitor cell-based approaches for improving regeneration in the adult mouse limbs.

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Generation of iPSC-derived limb progenitor-like cells for stimulating phalange regeneration in the adult mouse

Abstract

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