AI Article Synopsis

  • - Mesenchymal stromal cells (MSCs) are promising for cell therapy in various diseases due to their ability to secrete beneficial factors and modulate the immune system, but producing enough cells for clinical use is challenging.
  • - Suspension bioreactors combined with microcarriers allow for scalable MSC production, but traditional microcarriers often use animal proteins, raising regulatory concerns.
  • - A novel recombinant fusion protein was developed to attach growth factors to cellulose microcarriers without animal components, enhancing MSC growth and production in bioreactors while reducing costs and improving regulatory compliance.

Article Abstract

Mesenchymal stromal cells (MSCs) have the potential to be used as autologous or allogenic cell therapy in several diseases due to their beneficial secretome and capacity for immunomodulation and differentiation. However, clinical trials using MSCs require a large number of cells. As an alternative to traditional culture flasks, suspension bioreactors provide a scalable platform to produce clinically relevant quantities of cells. When cultured in bioreactors, anchorage-dependent cells like MSCs require the addition of microcarriers, which provide a surface for cell attachment while in suspension. The best performing microcarriers are typically coated in animal derived proteins, which increases cellular attachment and proliferation but present issues from a regulatory perspective. To overcome this issue, a recombinant fusion protein was generated linking basic fibroblast growth factor (bFGF) to a cellulose-specific carbohydrate binding module (CBM) and used to functionalize the surface of cellulose microcarriers for the expansion of human umbilical MSCs in suspension bioreactors. The fusion protein was shown to support the growth of MSCs when used as a soluble growth factor in the absence of cellulose, readily bound to cellulose microcarriers in a dose-dependent manner, and ultimately improved the expansion of MSCs when grown in bioreactors using cellulose microcarriers. The use of CBM fusion proteins offers a simple method for the surface immobilization of growth factors to animal component-free substrates such as cellulose, which can be used alongside bioreactors to increase growth factor lifespan, decrease culture medium cost, and increase cell production in the manufacturing of therapeutic cells.

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsabm.4c00513DOI Listing

Publication Analysis

Top Keywords

cellulose microcarriers
16
growth factor
16
suspension bioreactors
12
carbohydrate binding
8
binding module
8
fibroblast growth
8
expansion human
8
human umbilical
8
mesenchymal stromal
8
stromal cells
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!