A large-scale production of mesenchymal stem cells and their exosomes for an efficient treatment against lung inflammation

Mesenchymal stem cells (MSCs) and their produced exosomes have demonstrated inherent capabilities of inflammation-guided targeting and inflammatory modulation, inspiring their potential applications as biologic agents for inflammatory treatments. However, the clinical applications of stem cell therapies are currently restricted by several challenges, and one of them is the mass production of stem cells to satisfy the therapeutic demands in the clinical bench. Herein, a production of human amnion-derived MSCs (hMSCs) at a scale of over 1 x 109 cells per batch was reported using a three-dimensional (3D) culture technology based on microcarriers coupled with a spinner bioreactor system. The present study revealed that this large-scale production technology improved the inflammation-guided migration and the inflammatory suppression of hMSCs, without altering their major properties as stem cells. Moreover, these large-scale produced hMSCs showed an efficient treatment against the lipopolysaccharide (LPS)-induced lung inflammation in mice models. Notably, exosomes collected from these large-scale produced hMSCs were observed to inherit the efficient inflammatory suppression capability of hMSCs. The present study showed that 3D culture technology using microcarriers coupled with a spinner bioreactor system can be a promising strategy for the large-scale expansion of hMSCs with improved anti-inflammation capability, as well as their secreted exosomes. Production of therapeutic stem cells and their exosomes in a large scale is highly used in the clinical applications of stem cells therapy. In this study, a 3D cell expansion technology relying on microcarriers coupled with a spinner bioreactor system were studied for mass production of human amnion-derived mesenchymal stem cells at a scale with over 1 x 109 cells per batch. This 3D expansion technology had no detrimental impacts on the major properties of hMSCs compared to 2D expansion strategy, and significantly improved inflammation-guiled targeting and inflammatory suppression of produced hMSCs, such as a more potent inhibition of macrophage differentiation to the M1 pro-inflammatory phenotype. Both the 3D-produced hMSCs and their exosomes showed a more efficient suppression of the lipopolysaccharide-induced lung inflammation, suggesting the reported 3D expansion strategy held promises for large-scale production of hMSCs and their exosomes with good anti-inflammation capability. image