A fully automated bioreactor system for precise control of stem cell proliferation and differentiation

Abstract

The high proliferation ability and pluripotency of stem cells are ideal for application in stem cell therapy and tissue engineering. However, the clinical use of human mesenchymal stem cells (hMSCs) is limited due to the technical difficulties associated with mass production, high manufacturing costs, and contamination. Bioreactor systems can modulate the environmental and biochemical cues and also induce biomechanical cues, such as shear stress and hypoxia, during mass production of stem cells. In this study, we developed a fully automated bioreactor system (fABS) for precisely controlling the stem cell fate. We used this system for the proliferation and differentiation of human bone derived MSCs (hBMSCs). The fABS mainly consists of five systems: a monitoring system, the primary control system, a medium feeding system, a mass flow controller, and a cell culture system. We evaluated the precision with which the fABS regulated the stem cell environment. We observed that the shear stress induced by the fABS enhanced the hBMSC proliferation and osteogenic differentiation. Moreover, hypoxia induced by the fABS enhanced the chondrogenic differentiation of hBMSCs. As this system can have various applications, such as mass production, osteogenic differentiation, and chondrogenic differentiation, the fABS can aid in advancing the stem cell technologies.