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Human embryonic stem cell-derived mesenchymal cells preserve kidney function and
extend lifespan in NZB/W F1 mouse model of lupus nephritis
#MMPMID26628350
Thiel A
; Yavanian G
; Nastke MD
; Morales P
; Kouris NA
; Kimbrel EA
; Lanza R
Sci Rep
2015[Dec]; 5
(?): 17685
PMID26628350
show ga
Adult tissue-derived mesenchymal stromal cells (MSCs) are showing promise in
clinical trials for systemic lupus erythematosus (SLE). However, the inability to
manufacture large quantities of functional cells from a single donor as well as
donor-dependent variability in quality limits their clinical utility. Human
embryonic stem cell (hESC)-derived MSCs are an alternative to adult MSCs that can
circumvent issues regarding scalability and consistent quality due to their
derivation from a renewable starting material. Here, we show that hESC-MSCs
prevent the progression of fatal lupus nephritis (LN) in NZB/W F1 (BWF1) mice.
Treatment led to statistically significant reductions in proteinuria and serum
creatinine and preserved renal architecture. Specifically, hESC-MSC treatment
prevented disease-associated interstitial inflammation, protein cast deposition,
and infiltration of CD3(+) lymphocytes in the kidneys. This therapy also led to
significant reductions in serum levels of tumor necrosis factor alpha (TNF?) and
interleukin 6 (IL-6), two inflammatory cytokines associated with SLE.
Mechanistically, in vitro data support these findings, as co-culture of hESC-MSCs
with lipopolysaccharide (LPS)-stimulated BWF1 lymphocytes decreased lymphocyte
secretion of TNF? and IL-6, and enhanced the percentage of putative regulatory T
cells. This study represents an important step in the development of a
commercially scalable and efficacious cell therapy for SLE/LN.
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