RGD Reference Report - Action at a distance: systemically administered adult stem/progenitor cells (MSCs) reduce inflammatory damage to the cornea without engraftment and primarily by secretion of TNF-alpha stimulated gene/protein 6.

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Action at a distance: systemically administered adult stem/progenitor cells (MSCs) reduce inflammatory damage to the cornea without engraftment and primarily by secretion of TNF-alpha stimulated gene/protein 6.
Authors:	Roddy, GW Oh, JY Lee, RH Bartosh, TJ Ylostalo, J Coble, K Rosa RH, JR Prockop, DJ
Citation:	Roddy GW, etal., Stem Cells. 2011 Oct;29(10):1572-9. doi: 10.1002/stem.708.
RGD ID:	7777185
Pubmed:	PMID:21837654 (View Abstract at PubMed)
DOI:	DOI:10.1002/stem.708 (Journal Full-text)
Previous reports demonstrated that the deleterious effects of chemical injury to the cornea were ameliorated by local or systemic administration of adult stem/progenitor cells from bone marrow referred to as mesenchymal stem or stromal cells (MSCs). However, the mechanisms for the beneficial effects of MSCs on the injured cornea were not clarified. Herein, we demonstrated that human MSCs (hMSCs) were effective in reducing corneal opacity and inflammation without engraftment after either intraperitoneal (i.p.) or intravenous (i.v.) administration following chemical injury to the rat cornea. A quantitative assay for human mRNA for glyceraldehyde 3-phosphate dehydrogenase (GAPDH) demonstrated that less than 10 hMSCs were present in the corneas of rats 1-day and 3 days after i.v. or i.p. administration of 1 x 10(7) hMSCs. In vitro experiments using a transwell coculture system demonstrated that chemical injury to corneal epithelial cells activated hMSCs to secrete the multipotent anti-inflammatory protein TNF-alpha stimulated gene/protein 6 (TSG-6). In vivo, the effects of i.v. injection of hMSCs were largely abrogated by knockdown of TSG-6. Also, the effects of hMSCs were essentially duplicated by either i.v. or topical administration of TSG-6. Therefore, the results demonstrated that systemically administered hMSCs reduce inflammatory damage to the cornea without engraftment and primarily by secretion of the anti-inflammatory protein TSG-6 in response to injury signals from the cornea.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Inflammation	treatment	IMP		7777185	associated with Corneal Diseases	RGD
Inflammation	treatment	ISO	TNFAIP6 (Homo sapiens)	7777185; 7777185	associated with Corneal Diseases	RGD

Objects Annotated

Genes (Rattus norvegicus)

Tnfaip6 (TNF alpha induced protein 6)

Genes (Mus musculus)

Tnfaip6 (tumor necrosis factor alpha induced protein 6)

Genes (Homo sapiens)

TNFAIP6 (TNF alpha induced protein 6)

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Action at a distance: systemically administered adult stem/progenitor cells (MSCs) reduce inflammatory damage to the cornea without engraftment and primarily by secretion of TNF-alpha stimulated gene/protein 6.