Stem Cell-Based Cell Therapy for Glomerulonephritis

Table 1

Animal studies of stem cell therapy in glomerulonephritis (GN).

Authors (year)	Animal model (host)	Type of GN	Type of stem cell	Time of cell therapy	Dose and route of administration	Follow-up period after cell therapy	Outcomes	Reference number
Kunter et al. (2007)	Anti-Thy1,1 nephritis (Wistar/Lewis rats)	mesPGN	BM-MSCs	2 d after disease induction	2×10^6 cells left renal artery injection	10 d	↑recovery from mesangiolysis; ↑glomerular cell proliferation; ↓proteinuria	[17]
Rampino et al. (2011)	Anti-Thy1,1 nephritis (Sprague-Dawley rats)	mesPGN	BM-MSCs	3 d after anti-Thy1 injection	3×10^6 cells tail vein injection	11 d	↑renal function; ↓glomerular monocyte influx,; ↓renal injury	[18]
Sakr et al. (2013)	Anti-Thy1,1 nephritis (albino rats)	mesPGN	BM-MSCs	5 d after anti-Thy1 injection	1×10^6 cells tail vein injection	28 d	↓renal injury; ↓apoptosis, α-SMA; ↑renal function	[19]
Uchimura et al. (2005)	Anti-Thy1,1 nephritis (rats)	mesPGN	BMDCs	5 wk before anti-Thy1 antibody injection	5×10^7 cells tail vein injection	28 d	↑microvascular repair; ↑differentiation into glomerular endothelial and mesangial cell	[20]
Li et al. (2006)	Anti-Thy1,1 nephritis (rats)	mesPGN	BMDCs	5 wk before experimental progressive glomerulosclerosis	1-2×10^8 cells tail vein injection	12 wk	↑renal function; ↑improvement in glomerular hemodynamics; ↓renal injury	[21]
Uchimura et al. (2005)	Anti-Thy1,1 nephritis (Lewis rats)	mesPGN	BM-EPCs	1 d after antibody injection	1.0±0.2×10^6 cells left renal artery injection	6 d	↓glomerular injury score, the area positive for mesangial α-SMA, infiltration of macrophages	[20]
Tsuda et al. (2010)	Anti-Thy1,1 nephritis (Lewis rats)	mesPGN	FM-MSCs	2 d after anti-Thy1 antibody injection	5×10^5 cells tail vein injection	14 d	↓urinary protein excretion, activated mesangial cell, glomerular monocyte/macrophage infiltration, mesangial matrix accumulation, TNF-α, MCP-1, type I collagen, TGF-β, PAI-1	[22]
Abe-Yoshio et al. (2008)	Habu-snake venom-induced glomerulonephritis (TIE2/L mice)	mesPGN	BM-EPCs	On the same date of disease induced	1×10^6 cells tail vein injection	56 d	↓renal injury	[23]
Imasawa et al. (1999)	HIGA mice (high content of serum IgA)	IgA nephropathy	BMDCs		1×10^7 cells intravenously injection	26 wk	↓serum IgA; ↓renal injury	[14]
Imasawa and Utsunomiya (2002)	High serum level IgA ddY mice	IgA nephropathy	BM-MSCs	6 h after Gy injection	10×10^6 cells	26 wk	↓mesangial recipients of IgA and C3, glomerular sclerosis, IgA level	[24]
Ma et al. (2012)	MRL/lpr mice	LN	BM-MSCs		1×10^6 cells intravenous injection	26 wk	↓BAFF, IL-10; ↑TGF-β	[25]
Good et al. (2002)	BXSB mice and (NZW × BXSB) F1 W/BF1 mice	LN	Bone marrow cells HSC		15×10^6 cells	16 wk or 30 wk	↓renal injury	[26]
Gu et al. (2010)	MRL/lpr mice	LN	UC-MSCs	at the 18th, 19th, and 20th wk of age	1×10^6 cells		↑renal function; ↓renal injury; ↓MCP-1, HMGB-1	[27]
Chang et al. (2011)	NZB/W F1 mice	LN	UC-MSCs		1×10^6 cells tail vein injection	8 months	↑renal function; ↓renal injury; ↓TNF-α, IL-6, IL-12; ↓IL-4, IL-10	[28]
El-Ansary et al. (2012)	STZ-induced DN (C57BL/6 mice)	DN	BM-MSCs	25 d after the first; STZ dose	0.5×10^6 cells tail vein injection	62 d	↑renal function; normal histologically glomeruli	[29]
Zhou et al. (2009)	STZ-induced DN (Sprague-Dawley rats)	DN	BM-MSCs	4 wk after STZ	2×10^6 cells left cardiac ventricle	8 wk	↑renal function; ↓renal mass index	[30]
Ezquer et al. (2009)	STZ-induced DN (C57BL/6 mice)	DN	BM-MSCs	4 wk after STZ	2 doses of 0.5×10^6 cells tail vein injection	4 months	↓sclerosis, mesangial expansion, tubular dilatation, proteins cylinders, podocytes lost	[31]
Lv et al. (2013)	STZ-induced DN (Wistar rats)	DN	BM-MSCs	8 wk after establishment of diabetes model	2×10^6 tail vein injection	8 wk	↑renal function; ↓glomerulosclerosis, MCP-1, IL-1β, IL-6, TNFα	[32]
Thirabanjasak et al. (2010)	STZ-induced DN (Sprague-Dawley rats)	DN	BM-MSCs	4 wk after diabetes onset	1×10^6 cells; kidney-targeted ultrasound-targeted microbubble destruction	8 wk	↓renal damage; ↓TGF-β1; ↑synaptopodin, IL-10	[33]
Wang et al. (2013)	STZ-induced DN (Sprague-Dawley rats)	DN	BM-MSCs	30 d after diabetes induction by STZ injection	2×10^6 cells renal artery injection	60 d	↑renal function; ↓podocyte injury; ↑BMP-7	[34]
Chen et al. (2009)	db/db mice	DN	BMDCs		1×10^6 cells tail vein injection	50 d	↑renal function; ↓renal injury	[35]
Fang et al. (2012)	STZ-induced DN (Sprague-Dawley rats)	DN	AD-MSCs	4 wk after STZ injection	10×10^6 cells renal artery injection	12 wk	↓renal injury, oxidative damage; ↓p38, p-ERK, p-JNK	[36]
Masoad et al. (2012)	STZ-induced DN (rates)	DN	Mononuclear cells		150×10^6 cells/rat tail vein injection	8 wk	↓renal function; ↓renal injury	[37]
Magnasco et al. (2008)	ADR-induced nephropathy (Rats)	FSGS	BM-MSCs	Concomitantly to ADR/60 d after ADR	10×10^6 cells tail vein injection	24 h	↓podocytes apoptosis; ↓renal injury	[38]
Zoja et al. (2012)	ADR-induced nephropathy (Rats)	FSGS	BM-MSCs	36 h, 60 h, 3 d,; 5 d, 7 d, 14 d, and 21 d	2×10^6 cells tail vein injection	30 d	↓podocyte loss, apoptosis ↑preserve nephrin and CD2AP; ↑improvement in histological parameters	[39]
Ma et al. (2013)	ADR-induced nephropathy (Sprague-Daoley rats)	FSGS	Human UC-MSCs	1, 8, 15, and 22 d	2×10^6 cells tail vein injection	12 wk	↑improvement in clinical parameters and histology↓IL-6, TNF-α, CTGF; ↑IL-10	[40]
Meyer-Schwesinger; et al. (2011)	Puromycin; aminoglycoside and renal ablation models (Wistar rats)	FSGS	BM-EPCs	8 wk before model induced	2×10^6 cells intravenously injection	10 wk	↑renal function; ↓renal injury	[41]
Suzuki et al. (2013)	Wistar-Kyoto rats	Anti-GBM GN	Human BM-MSCs	4 d after rats induced	3×10^6 cells intravenous injection	13 d	↑improvement in functional and histological parameters; ↓collagen types I and III, TGF-β; ↓ED1-positive macrophages, CD8-positive cells, and TUNEL-positive apoptotic cells in glomeruli; ↓renal cortical mRNA for TNF-α, IL-1β, IL-17a; ↑renal cortical mRNA for TNF-α, IL-1β, IL-17, and serum IL-17A	[42]

mesPGN—mesangial proliferative glomerulonephritis.
LN—lupus nephritis.
STZ— streptozocin.
DN—Diabetic Nephropathy.
FSGS—Focal Segmental Glomerulosclerosis.
BM-MSCs—bone marrow mesenchymal stem cells.
BMDCs—bone marrow-derived cells.
BM-EPCs—bone marrow endothelial progenitors.
FM-MSCs—fetal membranes mesenchymal stem cells.
UC-MSC—umbilical cord mesenchymal stem cells.
AD-MSCs—adipose-derived mesenchymal stem cells.
α-SMA—α-smooth muscle actin.
BAFF—B-cell activating factor.
IL—interleukin.
TGF-β—transforming growth factor-β.
MCP-1—monocyte chemotactic protein-1.
HMGB-1—high-mobility group box 1.
TNF-α—tumour necrosis factor α.
BMP-7—bone morphogenic protein.
CTGF—connective tissue growth factor.