Journal article
Gastruloids enable modeling of the earliest stages of human cardiac and hepatic vascularization
Science (American Association for the Advancement of Science), Vol.388(6751), eadu9375
06/05/2025
DOI: 10.1126/science.adu9375
PMCID: PMC12815606
PMID: 40472086
Abstract
Although model organisms have provided insight into the earliest stages of cardiac and hepatic vascularization, we know very little about this process in humans because of ethical restrictions and the technical difficulty of obtaining embryos during very early development. In this study, we demonstrate that micropatterned human pluripotent stem cell-derived gastruloids enable in vitro modeling of the earliest stages of vascularization. We identify a combination of vascular-inducing factors that give rise to cardiac vascularized organoids with a spatially organized and branched vascular network. To show the broader utility of our vascularization strategy, we use the same vascular-inducing factors to produce hepatic vascularized organoids. Our results suggest that a conserved developmental program generates the vasculature within different types of organs.
Details
- Title: Subtitle
- Gastruloids enable modeling of the earliest stages of human cardiac and hepatic vascularization
- Creators
- Oscar J Abilez - Stanford UniversityHuaxiao Yang - Stanford UniversityYuan Guan - Stanford UniversityMengcheng Shen - Stanford UniversityZehra Yildirim - Stanford UniversityYan Zhuge - Stanford UniversityRavichandra Venkateshappa - Stanford UniversityShane R Zhao - Stanford UniversityAngello H Gomez - University of North TexasMarcel El-Mokahal - University of North TexasLogan Dunkenberger - Stanford UniversityYoshikazu Ono - Stanford UniversityMasafumi Shibata - Stanford UniversityPeter N Nwokoye - Stanford UniversityLei Tian - Stanford UniversityKitchener D Wilson - Stanford UniversityEvan H Lyall - Rosebud Biosciences, Orinda, CA, USAFangjun Jia - Stanford UniversityHung Ta Wo - Stanford UniversityGao Zhou - Stanford MedicineBryan Aldana - Stanford UniversityIoannis Karakikes - Stanford UniversityDetlef Obal - Stanford UniversityGary Peltz - Stanford MedicineChristopher K Zarins - Stanford UniversityJoseph C Wu - Stanford University
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.388(6751), eadu9375
- DOI
- 10.1126/science.adu9375
- PMID
- 40472086
- PMCID
- PMC12815606
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Publisher
- AMER ASSOC ADVANCEMENT SCIENCE
- Grant note
- NIH: K01HL130608, L30HL138771, R15HD108720, R56HL174856, T32GM136501, K08HL119251, R01HL150693, R01HL141371, R01HL146690, R01HL145676, R01HL176822, R01HL163680, R01HL171102, U01AI183953, P01HL141084, R01HL150414, R01HL139679, K99HL166693, R01DC021133, R24OD035408 American Heart Association Postdoctoral Fellowship Award: 18POST34030106 American Heart Association Fellowship Award: 23POST1021274 Tobacco-Related Disease Research Program (TRDRP): T33FT6330 California Institute for Regenerative Medicine grant: RC1-00151 Stanford Maternal & Child Health Research Institute Transdisciplinary Initiatives Program grantStanford Cardiovascular Institute seed grantStanford Bio-X Program support
This research was supported by NIH grants K01HL130608 and L30HL138771(O.J.A.); NIH grants R15HD108720 and R56HL174856 (H.Y.); NIH grant T32GM136501(A.H.G.); NIH grant K08HL119251(K.D.W.); NIH grants R01HL150693, R01HL141371, R01HL146690, R01HL145676,R01HL176822,R01HL163680, R01HL171102, U01AI183953, and P01HL141084 (J.C.W.); NIH grants R01HL150414 and R01HL139679 (I.K.); NIH grant K99HL166693 (M.S.) NIH grants R01DC021133 and R24OD035408 (G.P.); American Heart Association Postdoctoral Fellowship Award 18POST34030106 (H.Y.); American Heart Association Fellowship Award 23POST1021274 (Z.Y.); Tobacco-Related Disease Research Program (TRDRP) T33FT6330 (Z.Y.); California Institute for Regenerative Medicine grant RC1-00151(C.K.Z.); a Stanford Maternal & Child Health Research Institute Transdisciplinary Initiatives Program grant (O.J.A.); a Stanford Maternal & Child Health Research Institute Transdisciplinary Initiatives Program grant (D.O.); a Stanford Cardiovascular Institute seed grant (O.J.A. and H.Y.); and Stanford Bio-X Program support (O.J.A.).
- Language
- English
- Date published
- 06/05/2025
- Academic Unit
- Anesthesia
- Record Identifier
- 9984829026102771
Metrics
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