Potential surrogate quantitative immunomodulatory potency assay for monitoring human umbilical cord-derived mesenchymal stem cells production |
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Authors: | Sen-Wen Teng Hsin-Yu Sung Yu-Chieh Wen Ssu-Yu Chen Ronald Lovel Wen-Ying Chang Tang Bo-Chung Wu Yogi Cheng-Yo Hsuan Willie Lin |
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Institution: | 1. Department of Obstetrics and Gynecology, Cardinal Tien Hospital, New Taipei, Taiwan
School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan;2. Meribank Biotech Co., Ltd., Taipei, Taiwan;3. Meridigen Biotech Co., Ltd., Taipei, Taiwan;4. Meribank Biotech Co., Ltd., Taipei, Taiwan
Meridigen Biotech Co., Ltd., Taipei, Taiwan |
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Abstract: | Mesenchymal stem cells (MSCs) play an important role as immune modulator through interaction with several immune cells, including macrophages. In this study, the immunomodulatory potency of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) was demonstrated in the in vivo middle cerebral artery occlusion (MCAo)-induced brain injury rat model and in vitro THP-1-derived macrophages model. At 24 h after induction of MCAo, hUC-MSCs was administered via tail vein as a single dose. Remarkably, hUC-MSCs could inhibit M1 polarization and promote M2 polarization of microglia in vivo after 14 days induction of MCAo. Compared with THP-1-derived macrophages which had been stimulated by lipopolysaccharide, the secretion of proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interferon-γ inducible protein (IP-10), were significantly reduced in the presence of hUC-MSCs. Moreover, the secretion of anti-inflammatory cytokine, interleukin-10 (IL-10), was significantly increased after cocultured with hUC-MSCs. Prostaglandins E2 (PGE2), secreted by hUC-MSCs, is one of the crucial immunomodulatory factors and could be inhibited in the presence of COX2 inhibitor, NS-398. PGE2 inhibition suppressed hUC-MSCs immunomodulatory capability, which was restored after addition of synthetic PGE2, establishing the minimum amount of PGE2 required for immunomodulation. In conclusion, our data suggested that PGE2 is a crucial potency marker involved in the therapeutic activity of hUC-MSCs through macrophages immune response modulation and cytokines regulation. This study provides the model for the development of a surrogate quantitative potency assay of immunomodulation in stem cells production. |
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Keywords: | immunomodulation mesenchymal stem cells potency prostaglandins E2 |
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