4.7 Article

Efficient generation of hepatic cells from mesenchymal stromal cells by an innovative bio-microfluidic cell culture device

期刊

STEM CELL RESEARCH & THERAPY
卷 7, 期 -, 页码 -

出版社

BIOMED CENTRAL LTD
DOI: 10.1186/s13287-016-0371-7

关键词

Hepatocyte; Mesenchymal stromal cells; Hepatic differentiation; Microfluidic device

资金

  1. Novel Bioengineering and Technological Approaches to Solve Two Major Health Problems in Taiwan - the Taiwan Ministry of Science and Technology Academic Excellence Program [MOST 105-2633-B-009-003]
  2. Ministry of Science and Technology, Taiwan [MOST 103-2314-B-010-053-MY3, MOST 104-2321-B-010-008, MOST 105-2911-I-010-506]
  3. Aiming for the Top University Plan
  4. Ministry of Education

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Background: Mesenchymal stromal cells (MSCs) are multipotent and have great potential in cell therapy. Previously we reported the differentiation potential of human MSCs into hepatocytes in vitro and that these cells can rescue fulminant hepatic failure. However, the conventional static culture method neither maintains growth factors at an optimal level constantly nor removes cellular waste efficiently. In addition, not only is the duration of differentiating hepatocyte lineage cells from MSCs required to improve, but also the need for a large number of hepatocytes for cell therapy has not to date been addressed fully. The purpose of this study is to design and develop an innovative microfluidic device to overcome these shortcomings. Methods: We designed and fabricated a microfluidic device and a culture system for hepatic differentiation of MSCs using our protocol reported previously. The microfluidic device contains a large culture chamber with a stable uniform flow to allow homogeneous distribution and expansion as well as efficient induction of hepatic differentiation for MSCs. Results: The device enables real-time observation under light microscopy and exhibits a better differentiation efficiency for MSCs compared with conventional static culture. MSCs grown in the microfluidic device showed a higher level of hepatocyte marker gene expression under hepatic induction. Functional analysis of hepatic differentiation demonstrated significantly higher urea production in the microfluidic device after 21 days of hepatic differentiation. Conclusions: The microfluidic device allows the generation of a large number of MSCs and induces hepatic differentiation of MSCs efficiently. The device can be adapted for scale-up production of hepatic cells from MSCs for cellular therapy.

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