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Interleukin-1 receptor antagonist-mediated neuroprotection by umbilical cord-derived mesenchymal stromal cells following transplantation into a rodent stroke model.


ABSTRACT: The human umbilical cord is a promising source of mesenchymal stromal cells (MSCs). Intravenous administration of human umbilical cord-derived MSCs (IV-hUMSCs) showed a favorable effect in a rodent stroke model by a paracrine mechanism. However, its underlying therapeutic mechanisms must be determined for clinical application. We investigated the therapeutic effects and mechanisms of our good manufacturing practice (GMP)-manufactured hUMSCs using various cell doses and delivery time points in a rodent model of stroke. IV-hUMSCs at a dose of 1?×?106 cells at 24?h after stroke improved functional deficits and reduced neuronal damage by attenuation of post-ischemic inflammation. Transcriptome and immunohistochemical analyses showed that interleukin-1 receptor antagonist (IL-1ra) was highly upregulated in ED-1-positive inflammatory cells in rats treated with IV-hUMSCs. Treatment with conditioned medium of hUMSCs increased the expression of IL-1ra in a macrophage cell line via activation of cAMP-response element-binding protein (CREB). These results strongly suggest that the attenuation of neuroinflammation mediated by endogenous IL-1ra is an important therapeutic mechanism of IV-hUMSCs for the treatment of stroke.

SUBMITTER: Oh SH 

PROVIDER: S-EPMC5938060 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Interleukin-1 receptor antagonist-mediated neuroprotection by umbilical cord-derived mesenchymal stromal cells following transplantation into a rodent stroke model.

Oh Seung-Hun SH   Choi Chunggab C   Noh Jeong-Eun JE   Lee Nayeon N   Jeong Yong-Woo YW   Jeon Iksoo I   Shin Jeong-Min JM   Kim Ji-Hye JH   Kim Ho-Jin HJ   Lee Ji-Min JM   Kim Hyun-Sook HS   Kim Ok-Joon OJ   Song Jihwan J  

Experimental & molecular medicine 20180413 4


The human umbilical cord is a promising source of mesenchymal stromal cells (MSCs). Intravenous administration of human umbilical cord-derived MSCs (IV-hUMSCs) showed a favorable effect in a rodent stroke model by a paracrine mechanism. However, its underlying therapeutic mechanisms must be determined for clinical application. We investigated the therapeutic effects and mechanisms of our good manufacturing practice (GMP)-manufactured hUMSCs using various cell doses and delivery time points in a  ...[more]

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