Optically Promoting Cardiac Maturation Using Engineered Peptides
Optically Promoting Cardiac Maturation Using Engineered Peptides
批准号:
10683790
负责人:
Herdeline Ann Mallari Ardoña
金额:
$49.49万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-09-12 至 2023-08-31
关键词:
Action PotentialsAddressAdultAnimal ModelArchitectureAutomobile DrivingBehaviorBindingBiologicalBiophysicsCalciumCardiacCardiac MyocytesCardiovascular DiseasesCardiovascular systemCell Culture TechniquesCell SurvivalCellsChargeChemical StimulationCuesDrug ScreeningElectric StimulationElectrodesEngineeringEnsureEpitopesFilmFrequenciesFunctional disorderGene ExpressionGenerationsGoalsHeart DiseasesHeart InjuriesHeatingHumanIn VitroInvestigationLightMeasurementMeasuresMechanical StimulationMechanicsMediatingMetabolismMethodsMicroelectrodesModelingMonitorMuscle CellsMyocardiumNanostructuresNeonatalOpticsPeptide LibraryPeptidesPhenotypePhysiologic pulsePolymersProcessProtocols documentationRattusReportingResearchResolutionRisk AssessmentSignal TransductionSiteSourceStimulusStressStructureSurfaceTechnologyTestingTherapeuticTissuesToxicologyTransducersTransfectionVentricularbasebiomaterial interfacecardiac pacingcardiac regenerationcardiac tissue engineeringchromophoreconditioningdesigndisease mechanisms studydrug discoveryelectric fieldextracellulargenetically modified cellshigh throughput screeninghuman stem cellsimprovedindexinginduced pluripotent stem cellinfection riskinnovationinstrumentationirradiationminimally invasivemonomernanoassemblynon-geneticnovel strategiesoptogeneticspersonalized medicineregenerative therapyresponsescale upspatiotemporalspecies differencestemstem cell based approachstem cellssuccesstemporal measurementwireless
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
The promise of human stem cell-derived cardiomyocytes (hSC-CMs) opens doors towards the
feasibility of personalized medicine against cardiac diseases and for performing more accurate drug
discovery studies. Moreover, hSC-CMs overcome the issue of species differences when using animal
models for high throughput screening studies. However, one of the bottlenecks for scaling up the use of
hSC-CMs is their ability to accurately reflect the native structure and function of adult human
cardiomyocytes. Current efforts to address this critical challenge involve maturation protocols that use
biophysical cues such as electrical and mechanical stimulation. These methods often utilize electrode
contacts for field stimulation, bulky instrumentation for mechanical or sustained chemical stimulation, or
genetically modifying cells to be light-responsive. Although we have seen successes through these
induction and stimulation approaches, the field would benefit from a stimulation approach with minimal
culture contact to reduce risk of infection during long-term cultures, as well as a light-based approach
with higher spatiotemporal resolution than electrode-based stimulation. Here, we propose a new
paradigm for stimulating hSC-CMs towards maturation by interfacing these cells with peptide-based
substrates that are engineered to convert light to electrical cues. Our team will develop peptides
engineered with chromophore units and cell-binding epitopes as materials that can be used for
photoelectrical conditioning of hSC-CMs towards maturation. The long-term goal of this project is to
establish photoelectrical conditioning via engineered peptides as a viable method to electrically stimulate
cardiomyocytes and promote hSC-CM maturation in an electrodeless and non-genetic manner, with
higher spatiotemporal resolution than field stimulation. We hypothesize that transient charging and other
associated light-induced processes at the cardiomyocyte-biomaterial interface can influence extracellular
potential, resulting in the photoelectrical stimulation of hSC-CMs towards maturation. Our rationale for
proposing a materials-based approach for stimulating hSC-CMs stems from previous reports of
conjugated polymers being used as a photoactive substrate for triggering action potentials of other
excitable cells. To test our hypothesis, we propose the following specific aims: (1) establishing design
parameters for peptide nanoassemblies with optimal photostimulation efficiency; (2) test the cellular- and
tissue-level impact of peptide-mediated photostimulation; and (3) elucidate the effect of the proposed
photoelectrical conditioning method on hSC-CM maturation. By establishing the design rules for the
proposed photoexcitable peptides for stimulating hSC-CMs and ensuring their capability to locally excite
cardiac cells, this innovative approach offers a new strategy for a “wireless” stimulation of cardiac tissues
and can significantly contribute towards addressing the grand challenge of stem cell immaturity.
1
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Optically Promoting Cardiac Maturation Using Engineered Peptides
-
批准号:10628281
-
项目类别:
-
资助金额:$50.12万
-
财政年份:2023
-
负责人:Herdeline Ann Mallari Ardoña
-
依托单位:
海外基金