RT Journal Article
SR Electronic
T1 Self-assembly of progenitor cells under the aegis of platelet factors facilitates human skin organoid formation and vascularized wound healing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.10.292409
DO 10.1101/2020.09.10.292409
A1 Patricia Peking
A1 Linda Krisch
A1 Martin Wolf
A1 Anna Hoog
A1 Balázs Vári
A1 Katharina Muigg
A1 Rodolphe Poupardin
A1 Cornelia Scharler
A1 Elisabeth Russe
A1 Harald Stachelscheid
A1 Achim Schneeberger
A1 Katharina Schallmoser
A1 Dirk Strunk
YR 2020
UL http://biorxiv.org/content/early/2020/09/11/2020.09.10.292409.abstract
AB Stem/progenitor cells can self-organize into organoids modelling tissue function and regeneration. Here we demonstrate that human platelet-derived factors can orchestrate 3D self-assembly of clonally expanded adult skin fibroblasts, keratinocytes and endothelial progenitors forming skin organoids within three days. Organoids showed distinct signaling patterns in response to inflammatory stimuli that clearly differed from separated cell types. Human induced pluripotent stem cell (hiPSC)-derived skin cell progenitors also self-assembled into stratified human skin within two weeks, healing deep wounds of immune-deficient mice. Co-transplantation of endothelial progenitors significantly accelerated vascularization. Mechanistically, platelet-derived extracellular vesicles mediated the platelet-derived trophic effects. Long-term fitness of epidermal cells was accelerated further by keratinocyte growth factor mRNA transfection. No tumorigenesis was observed upon xenografting. This permits novel rapid 3D skin-related pharmaceutical testing opportunities and facilitates development of iPSC-based skin regeneration strategies.Competing Interest StatementAchim Schneeberger is an employee of accanis.com, a company planning to commercialize mRNA therapy.