TY  - GEN
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/36468/
A1  - Akinbote, Akinola
ID  - heidok36468
N2  - Studying  the  myocardial  microvasculature  has  been  challenging,  in  part,  due  to  technical  
imaging limitations in vivo and limited physiologically relevant in vitro models.  This thesis reports 
the development of two on-chip models of human microvasculature to study the impact of the tissue 
microenvironment  on  cardiac  vascular  remodeling?with  a  specific  focus  on  the  contributions  of  
stromal cells, cardiomyocytes, and female sex hormones in regulating microvascular behavior. First, 
the  effect  of  vascular-stromal  crosstalk  was  studied  by  assessing  the  impact  of  tissue-specific  co-
cultured  fibroblasts  on  microvascular  development.  The  results  presented  herein,  demonstrate  that  
fibroblasts  impact  microvascular  morphology  by  increasing  branch  density  while  decreasing  vessel  
diameter. Cardiac fibroblasts, unlike lung fibroblasts, cause a reduction in vascular barrier function. 
Moreover, lung and cardiac fibroblasts had a differential response to TGF?1, mimicking different 
aspects  of  fibrosis  on-chip.  This  published  first  work  highlighted  the  importance  of  fibroblasts  in  
developing  tissue-specific  models  for  vascular  research.  Next,  a  3D  model  that  mimics  coronary  
microvascular  structure  and  barrier  function  was  developed  to  explore  vascular-myocyte  crosstalk.  
Human-induced pluripotent stem cell (hiPSC)-derived cardiac spheroids (CS) were co-cultured with 
cardiac  microvasculature  to  assess  the  impact  of  myocyte  crosstalk  on  microvessel  development.  
Cardiomyocytes  altered  vessel  morphology  and  improved  barrier  function  in  a  spatially  dependent  
manner. This vascularized cardiac model was used to investigate the cardioprotective roles of the sex 
hormones  estrogen  (E2)  and  progesterone  (P4)  under  inflammatory  conditions.  Pre-treatment  with  
these hormones preserves endothelial barrier integrity during TNF?-induced inflammation, potentially 
by  modulating  endothelin-1  secretion.  Overall,  these  models  highlight  the  critical  role  of  cellular  
crosstalk  and  the  tissue  microenvironment  in  vascular  development  and  showcase  their  utility  in  
modeling vascular perturbations.
CY  - Heidelberg
N1  - Dr. Kristina Haase was my direct supervisor at EMBL Barcelona. | 

The thesis defense committee was composed of:
Prof. Dr. Markus Hecker
Dr. Vikas Trivedi
Prof.Dr. Stefan Wolf
Dr. Mahak Singhal

| The thesis advisory committee was composed of:
Prof. Dr. Markus Hecker
Dr. Vikas Trivedi
Dr. Theodore Alexandrov
Dr. Gregana Dobreva
Y1  - 2026///
TI  - Engineered Models of Human Microvasculature: Investigating the Cardiac Microenvironment?s Role in Vascular 
Remodeling
AV  - restricted
ER  -