Large-Scale Expansion of Human Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) are multipotent stem cells with strong immunosuppressive property that renders them an attractive source of cells for cell therapy. MSCs have been studied in multiple clinical trials to treat liver diseases, peripheral nerve damage, graft-versus-host disease, autoimmune diseases, diabetes mellitus, and cardiovascular damage. Millions to hundred millions of MSCs are required per patient depending on the disease, route of administration, frequency of administration, and patient body weight. Multiple large-scale cell expansion strategies have been described in the literature to fetch the cell quantity required for the therapy. In this review, bioprocessing strategies for large-scale expansion of MSCs were systematically reviewed and discussed. The literature search in Medline and Scopus databases identified 26 articles that met the inclusion criteria and were included in this review. These articles described the large-scale expansion of 7 different sources of MSCs using 4 different bioprocessing strategies, i.e., bioreactor, spinner flask, roller bottle, and multilayered flask. The bioreactor, spinner flask, and multilayered flask were more commonly used to upscale the MSCs compared to the roller bottle. Generally, a higher expansion ratio was achieved with the bioreactor and multilayered flask. Importantly, regardless of the bioprocessing strategies, the expanded MSCs were able to maintain its phenotype and potency. In summary, the bioreactor, spinner flask, roller bottle, and multilayered flask can be used for large-scale expansion of MSCs without compromising the cell quality.

Figure 1

Flow chart of article selection process.

Figure 2

Frequency of the mesenchymal stem cell (MSC) sources in the selected articles. Most of the studies expanded the MSCs derived from bone marrow, adipose tissue, and Wharton's jelly. BM: bone marrow; AT: adipose tissue; WJ: Wharton's jelly; PD: periosteum; VC: villous chorion; F: fetal; DP: dental pulp.

Figure 3

Frequency of the bioprocessing strategies used in the selected studies. Most of the studies used bioreactor, spinner flask, and multilayered flask for large-scale expansion of MSCs.

Figure 4

Expansion ratios achieved using different bioprocessing strategies. Multilayered flask and bioreactor can achieve higher expansion ratio compared to spinner flask and roller bottle.