Can mRNA technology disrupt conventional approaches for discovering and validating in vivo new therapeutic targets?
Cardiogenic growth factors play important roles in heart development and in a new study published in the scientific paper Nature Communications from researchers at Karolinska Institutet shows how stem cell therapeutics and mRNA technology are beginning to converge offering major improvements in vascularization, survival, expansion, differentiation, and ultimately the function of human stem cell grafts.
"We report a new study which uses a combination of single cell sequencing and in vitro and in vivo screening of a library of defined secreted factors derived from human heart progenitors, to document a dual effect on vasculogenesis and cardiogenesis, uncovering a new potential therapeutic role of placental growth factor.
The study suggests that biased mRNA libraries could lead to quickly identifying secreted factors that can drive cell fate decisions in vivo with a single injection" says the senior author Kenneth R. Chien senior professor at the Department of Cell and Molecular Biology.
“The study paves the way for further developing novel therapeutic strategies combined with mRNA and heart progenitors for heart regeneration and repair" says the last author Makoto Sahara, Senior Research Specialist at the Department of Cell and Molecular Biology.
This work was supported by research grants: to K.R.C. from the Swedish Research Council Research collaboration grant China-Sweden (Dnr: 539-2013-7002); the Swedish Research Council Distinguished Professor Grant (Dnr: 541-2013-8351); and the Knut and Alice Wallenberg Foundation (Dnr: 2013.0028); and to M.S. from the Swedish Research Council (Dnr: 2019-01359); the Swedish Heart and Lung Foundation (Dnr: 20150421 and 20190380); and Karolinska Institutet (Strategic Research Area Stem Cells and Regenerative Medicine 2020).
Placental growth factor exerts a dual function for cardiomyogenesis and vasculogenesis during heart development.
Witman N, Zhou C, Häneke T, Xiao Y, Huang X, Rohner E, Sohlmér J, Grote Beverborg N, Chien KR, Sahara M
Nat Commun 2023 Sep;14(1):5435