Superior Alignment of Human iPSC-Osteoblasts Associated with Focal Adhesion Formation Stimulated by Oriented Collagen Scaffold.

Ryosuke Ozasa,Aira Matsugaki,Takayoshi Nakano,Hui-Suk Yun,Tadaaki Matsuzaka,Takuya Ishimoto

doi:10.3390/ijms22126232

Ryosuke Ozasa, Aira Matsugaki + Show 4 more

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https://doi.org/10.3390/ijms22126232

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Abstract

Human-induced pluripotent stem cells (hiPSCs) can be applied in patient-specific cell therapy to regenerate lost tissue or organ function. Anisotropic control of the structural organization in the newly generated bone matrix is pivotal for functional reconstruction during bone tissue regeneration. Recently, we revealed that hiPSC-derived osteoblasts (hiPSC-Obs) exhibit preferential alignment and organize in highly ordered bone matrices along a bone-mimetic collagen scaffold, indicating their critical role in regulating the unidirectional cellular arrangement, as well as the structural organization of regenerated bone tissue. However, it remains unclear how hiPSCs exhibit the cell properties required for oriented tissue construction. The present study aimed to characterize the properties of hiPSCs-Obs and those of their focal adhesions (FAs), which mediate the structural relationship between cells and the matrix. Our in vitro anisotropic cell culture system revealed the superior adhesion behavior of hiPSC-Obs, which exhibited accelerated cell proliferation and better cell alignment along the collagen axis compared to normal human osteoblasts. Notably, the oriented collagen scaffold stimulated FA formation along the scaffold collagen orientation. This is the first report of the superior cell adhesion behavior of hiPSC-Obs associated with the promotion of FA assembly along an anisotropic scaffold. These findings suggest a promising role for hiPSCs in enabling anisotropic bone microstructural regeneration.

Highlights

Introduction published maps and institutional affilStem cell-based therapies and research have attracted attention as sources of novel bone regeneration techniques in orthopedics
The present study focused on comparing normal human osteoblasts (NHObs) and Human-induced pluripotent stem cells (hiPSCs) in terms of the regulation of cell alignment responses to an anisotropic scaffold
HiPSCs were harvested on inactivated SNL feeder cells to maintain them in an undifferentiated state

Summary

Introduction

Stem cell-based therapies and research have attracted attention as sources of novel bone regeneration techniques in orthopedics. Current therapeutic options for bone disorders and defects include the application of bone marrow-derived mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). IPSCs, which are pluripotent cells reprogrammed from somatic cells [1,2], are a promising cell source for regenerative medicine, as they exhibit renewability and pluripotency [3,4,5], and overcome the limited availability of autologous MSCs [6]. Many studies have reported the differentiation of iPSCs into osteoblasts and the generation of bone substitutes under treatment with bioactive molecules. Bone morphogenetic proteins (BMPs), calcium-regulating vitamin iations

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