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Stiffness Mediated Reprogramming Efficiency Improvement

Substrate stiffness is one of the most widely used physical signals regulating stem cell differentiation. Creative Bioarray is dedicated to controlling iPSC production through stiffness control for future applications or exploring new methods of stiffness-mediated enhancement of direct cell reprogramming efficiency. Our professional scientific services will accelerate your research in the field of cell reprogramming.

Introduction

The presence of adult stem cells in tissues is insured by a specific microenvironment that includes soluble signaling factors, cell-cell, and extracellular matrix (ECM) interactions, and biomechanical properties of the ECM such as viscosity, elasticity, and nanotopography. Among these, the stiffness of the microenvironment has a key role in cell differentiation. Stiffer substrates have been shown to facilitate osteogenesis, while soft substrates facilitate the differentiation of human bone marrow mesenchymal stem cells (MSCs) into adipocytes or neurons. Moreover, matrix stiffness can also regulate the cell reprogramming process.

Recently, it has been proposed that soft polyacrylamide hydrogels with stiffness as low as 0.1 kPa can facilitate the reprogramming process of MEF into mouse iPSCs. Another related study reported the optimal stiffness for human and mouse iPSCs generation in 3D polyethylene glycol (PEG) hydrogels. Mechanistic studies have shown that substrate stiffness can alter cell adhesion and cytoskeletal reorganization, thereby activating signaling pathways that regulate gene expression to alter cell behavior. However, at present, the potential molecular mechanisms by which stiffness regulates cellular reprogramming still need further investigation.

Substrate stiffness activates intracellular pathways and cytoskeletal organization to influence cell behavior.Fig.1 Substrate stiffness activates intracellular pathways and cytoskeletal organization to influence cell behavior. (Long, 2017)

Technical Support

Researchers at Creative Bioarray have focused on exploring the possibility of synthesizing "reprogramming niche" to improve reprogramming efficiency by controlling substrates stiffness to more accurately tune and mimic the stiffness of the in vivo microenvironment. We provide technical support to our clients including but not limited to:

  • We have developed soft substrates comparable with natural myocardium, which further enhance reprogramming of Sendai virus vectors through YAP/TAZ inhibition, ultimately improving the efficiency and quality of cardiac reprogramming.
  • We developed soft substrates (1.5 or 15 kPa polydimethylsiloxane-PDMS) which facilitate stem cell phenotyping and promote reprogramming of human mesenchymal stem/stromal cells (hMSC) via mechanical transduction.

Applications

  • Development of regenerative medicine
  • Study on creating human tissue alternatives
  • Research on simulating native tissue structure and function

Our Advantages

  • Abundant experience and state-of-the-art facilities
  • Professional and reliable technical support
  • Providing start-to-finish scientific assistance throughout the entire project

As a technology company specializing in cell reprogramming services for many years, Creative Bioarray has continued to innovate reprogramming technologies to meet the needs of our customers. We help our customers enhance the initiation of cell reprogramming by controlling substrate stiffness to ultimately lead to efficient and reproducible iPSCs production. Please contact us directly with your research needs and we will provide you with the most suitable solution.

Reference

  1. Long, J.; et al. A biomaterial approach to cell reprogramming and differentiation. Journal of Materials Chemistry B. 2017, 5(13): 2375-2389.
For Research Use Only. Not For Clinical Use.