Abstract

Humanpluripotentstemcellderivedendothelialcells(hPSC-ECs)andpericytesareanidealautologouscell sourceforuseinvasculartherapies.ECslinetheinnerlayerofthevasculatureandpericytesprovidesupport tosmalldiametervesselsinordertoregulatevascularpermeability.DerivationofthesecellsfromhPSCs requirestimesensitivedeliveryofgrowthfactorsandsmallmoleculesinordertoinducevascularfate. Characterizationofthesecellsisoftenlimitedto2Dinvitroassaysandcellsurfaceproteinverification.Aswe movetowardstherapeuticuse,functionalcharacterizationisnecessarytoensuretheirtranslationalefficiency andefficacy.HypoxiahasbeenshowntobeakeyregulatorofECfate,neovascularization,andregeneration. However,itsroleinvascularstabilizationthroughpericyterecruitmenthasnotbeenstudied.Here,thorough analysisofhPSC-ECsandpericytesinhypoxicenvironmentsweaimto:(1)StudynetworkkineticsofhPSC- ECsin3Dlowoxygenenvironments,(2)studyhPSC-ECsandhPSC-pericyteinteractionsinhypoxiainvitro, and(3)StudyhPSC-EC-pericyteinteractionsinamouseoxygeninducedretinopathymodel.
These aims requireamultidisciplinaryapproach,interfacingstemcellandvascularbiologywithtissueengineering. SuccessfulcompletionoftheseaimswillbroadenourunderstandingofhPSC-ECsandpericytesbehavior towardstherapeuticmodalities.

Public Health Relevance

Humanpluripotentstemcellsareaviablesourcetoderivecellsforvasculartherapies.Clearunderstandingof howthesecellsrespondtophysiologicallyrelevantcuesisvitalforfunctionalcharacterization.Here,we proposeworkintounderstandinghowhumanpluripotentstemcellderivedvascularcellsrespondtohypoxiain vitroandinvivo.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31HL143972-03
Application #
9954138
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lidman, Karin Fredriksson
Project Start
2018-07-01
Project End
2023-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205