A Dense Fibrillar Collagen Scaffold Differentially Modulates Secretory Function of iPSC-Derived Vascular Smooth Muscle Cells to Promote Wound Healing.

Biraja C Dash,Hassan Peyvandi,Francois Berthiaume,Ocean Setia,Henry C Hsia,Alan Dardik,Jolanta Gorecka,Lara Lopes,James Nie,Kaiti Duan

doi:10.3390/cells9040966

Abstract

The application of human-induced pluripotent stem cells (hiPSCs) to generate vascular smooth muscle cells (hiPSC-VSMCs) in abundance is a promising strategy for vascular regeneration. While hiPSC-VSMCs have already been utilized for tissue-engineered vascular grafts and disease modeling, there is a lack of investigations exploring their therapeutic secretory factors. The objective of this manuscript was to understand how the biophysical property of a collagen-based scaffold dictates changes in the secretory function of hiPSC-VSMCs while developing hiPSC-VSMC-based therapy for durable regenerative wound healing. We investigated the effect of collagen fibrillar density (CFD) on hiPSC-VSMC’s paracrine secretion and cytokines via the construction of varying density of collagen scaffolds. Our study demonstrated that CFD is a key scaffold property that modulates the secretory function of hiPSC-VSMCs. This study lays the foundation for developing collagen-based scaffold materials for the delivery of hiPSC-VSMCs to promote regenerative healing through guiding paracrine signaling pathways.

Highlights

Human-induced pluripotent stem cells and their ability to differentiate into vascular smooth muscle cells have revolutionized the field of vascular tissue engineering [1,2,3,4].human-induced pluripotent stem cells (hiPSCs) provide an unlimited cell source for large-scale generation of a functional and pure population of lineage- and patient-specific VSMCs without ethical concerns [3,5,6,7]. hiPSC-VSMCs exhibiting disease phenotypes have been utilized to engineer in vitro disease models [6,8,9,10]
Our study suggests that an increase in collagen fibrillar density (CFD) improves cell survival and differentially regulates hiPSC-VSMCs paracrine function. hiPSC-VSMCs produced cytokines that promote angiogenesis, immunomodulation, and wound healing
Integration-free hiPSCs derived from neonatal fibroblasts were used for differentiation to VSMCs according to the previous protocol [6]

Summary

Introduction

Human-induced pluripotent stem cells (hiPSCs) and their ability to differentiate into vascular smooth muscle cells (hiPSC-VSMCs) have revolutionized the field of vascular tissue engineering [1,2,3,4].hiPSCs provide an unlimited cell source for large-scale generation of a functional and pure population of lineage- and patient-specific VSMCs without ethical concerns [3,5,6,7]. hiPSC-VSMCs exhibiting disease phenotypes have been utilized to engineer in vitro disease models [6,8,9,10]. HiPSC-VSMCs exhibiting disease phenotypes have been utilized to engineer in vitro disease models [6,8,9,10] In addition to their use in disease modeling, hiPSC-VSMCS have been exploited to build tissue-engineered vascular grafts [11,12,13,14,15]. Ren et al perfused a decellularized lung matrix with hiPSC-derived endothelial cells (ECs) and VSMCs to create a functional endothelium [19]. These preliminary reports encourage further in-depth study to explore the secretory function of hiPSC-VSMCs in extracellular-based matrix (ECM) environment

Methods

Results

Discussion

Conclusion