IL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model

Mesenchymal stem cells (MSCs) are used in various studies to induce immunomodulatory effects in clinical conditions associated with immune dysregulation such as graft versus host disease (GvHD). However, most of these clinical trials failed to go beyond early phase 2 studies because of limited effic...

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Autores principales:	Cuiping Zhang, Mina Delawary, Peng Huang, Jennifer A. Korchak, Koji Suda, Abba C. Zubair
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mRNA engineered MSCs interleukin 10 immunosuppression graft versus host disease Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/51a8916a21044af2ac4c6c0f1c2489c4
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spelling	oai:doaj.org-article:51a8916a21044af2ac4c6c0f1c2489c42021-11-25T17:11:31ZIL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model10.3390/cells101131012073-4409https://doaj.org/article/51a8916a21044af2ac4c6c0f1c2489c42021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3101https://doaj.org/toc/2073-4409Mesenchymal stem cells (MSCs) are used in various studies to induce immunomodulatory effects in clinical conditions associated with immune dysregulation such as graft versus host disease (GvHD). However, most of these clinical trials failed to go beyond early phase 2 studies because of limited efficacy. Various methods have been assessed to increase the potency of MSCs. IL-10 is an anti-inflammatory cytokine that is known to modulate immune responses in GvHD. In this study, we evaluated the feasibility of transfecting IL-10 mRNA to enhance MSC therapeutic potential. IL-10 mRNA engineered MSCs (eMSCs-IL10) maintained high levels of IL-10 expression even after freezing and thawing. IL-10 mRNA transfection did not appear to alter MSC intrinsic characteristics. eMSCs-IL10 significantly suppressed T cell proliferation relative to naïve MSCs in vitro. In a mouse model for GvHD, eMSCs-IL10 induced a decrease in plasma level of potent pro-inflammatory cytokines and inhibited CD4+ and CD8+ T cell proliferation in the spleen. In summary, our studies demonstrate the feasibility of potentiating MSCs to enhance their immunomodulatory effects by IL-10 mRNA transfection. The use of non-viral transfection may generate a safe and potent MSC product for treatment of clinical conditions associated with immune dysregulation such as GvHD.Cuiping ZhangMina DelawaryPeng HuangJennifer A. KorchakKoji SudaAbba C. ZubairMDPI AGarticlemRNA engineered MSCsinterleukin 10immunosuppressiongraft versus host diseaseBiology (General)QH301-705.5ENCells, Vol 10, Iss 3101, p 3101 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mRNA engineered MSCs interleukin 10 immunosuppression graft versus host disease Biology (General) QH301-705.5
spellingShingle	mRNA engineered MSCs interleukin 10 immunosuppression graft versus host disease Biology (General) QH301-705.5 Cuiping Zhang Mina Delawary Peng Huang Jennifer A. Korchak Koji Suda Abba C. Zubair IL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model
description	Mesenchymal stem cells (MSCs) are used in various studies to induce immunomodulatory effects in clinical conditions associated with immune dysregulation such as graft versus host disease (GvHD). However, most of these clinical trials failed to go beyond early phase 2 studies because of limited efficacy. Various methods have been assessed to increase the potency of MSCs. IL-10 is an anti-inflammatory cytokine that is known to modulate immune responses in GvHD. In this study, we evaluated the feasibility of transfecting IL-10 mRNA to enhance MSC therapeutic potential. IL-10 mRNA engineered MSCs (eMSCs-IL10) maintained high levels of IL-10 expression even after freezing and thawing. IL-10 mRNA transfection did not appear to alter MSC intrinsic characteristics. eMSCs-IL10 significantly suppressed T cell proliferation relative to naïve MSCs in vitro. In a mouse model for GvHD, eMSCs-IL10 induced a decrease in plasma level of potent pro-inflammatory cytokines and inhibited CD4+ and CD8+ T cell proliferation in the spleen. In summary, our studies demonstrate the feasibility of potentiating MSCs to enhance their immunomodulatory effects by IL-10 mRNA transfection. The use of non-viral transfection may generate a safe and potent MSC product for treatment of clinical conditions associated with immune dysregulation such as GvHD.
format	article
author	Cuiping Zhang Mina Delawary Peng Huang Jennifer A. Korchak Koji Suda Abba C. Zubair
author_facet	Cuiping Zhang Mina Delawary Peng Huang Jennifer A. Korchak Koji Suda Abba C. Zubair
author_sort	Cuiping Zhang
title	IL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model
title_short	IL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model
title_full	IL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model
title_fullStr	IL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model
title_full_unstemmed	IL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model
title_sort	il-10 mrna engineered mscs demonstrate enhanced anti-inflammation in an acute gvhd model
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/51a8916a21044af2ac4c6c0f1c2489c4
work_keys_str_mv	AT cuipingzhang il10mrnaengineeredmscsdemonstrateenhancedantiinflammationinanacutegvhdmodel AT minadelawary il10mrnaengineeredmscsdemonstrateenhancedantiinflammationinanacutegvhdmodel AT penghuang il10mrnaengineeredmscsdemonstrateenhancedantiinflammationinanacutegvhdmodel AT jenniferakorchak il10mrnaengineeredmscsdemonstrateenhancedantiinflammationinanacutegvhdmodel AT kojisuda il10mrnaengineeredmscsdemonstrateenhancedantiinflammationinanacutegvhdmodel AT abbaczubair il10mrnaengineeredmscsdemonstrateenhancedantiinflammationinanacutegvhdmodel
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IL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model

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