Pro-angiogenic Potential of Mesenchymal Stromal Cells Regulated by Matrix Stiffness and Anisotropy Mimicking Right Ventricles.
Michael Nguyen-TruongSeungil KimCourtney DohertyMegan FrederesKristen LeBarSoham GhoshPeiman HemattiRaghavan ChinnaduraiWilliam R WagnerZhijie WangPublished in: Biomacromolecules (2022)
Capillary rarefaction is a hallmark of right ventricle (RV) failure. Mesenchymal stromal cell (MSC)-based therapy offers a potential treatment due to its pro-angiogenic function. However, the impact of RV tissue mechanics on MSC behavior is unclear, especially when referring to RV end-diastolic stiffness and mechanical anisotropy. In this study, we assessed MSC behavior on electrospun scaffolds with varied stiffness (normal vs failing RV) and anisotropy (isotropic vs anisotropic). In individual MSCs, we observed the highest vascular endothelial growth factor (VEGF) production and total tube length in the failing, isotropic group (2.00 ± 0.37, 1.53 ± 0.24), which was greater than the normal, isotropic group (0.70 ± 0.15, 0.55 ± 0.07; p < 0.05). The presence of anisotropy led to trends of increased VEGF production on normal groups (0.75 ± 0.09 vs 1.20 ± 0.17), but this effect was absent on failing groups. Our findings reveal synergistic effects of RV-like stiffness and anisotropy on MSC pro-angiogenic function and may guide MSC-based therapies for heart failure.
Keyphrases
- mycobacterium tuberculosis
- vascular endothelial growth factor
- bone marrow
- heart failure
- endothelial cells
- anti inflammatory
- single cell
- left ventricular
- stem cells
- mesenchymal stem cells
- tissue engineering
- human health
- pulmonary hypertension
- gene expression
- pulmonary artery
- genome wide
- drug delivery
- risk assessment
- atrial fibrillation
- ejection fraction
- congenital heart disease
- combination therapy
- cardiac resynchronization therapy
- pulmonary arterial hypertension