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2016 ; 46
(1
): 75-82
Nephropedia Template TP
gab.com Text
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Human Adipose Stromal Cells Increase Survival and Mesenteric Perfusion Following
Intestinal Ischemia and Reperfusion Injury
#MMPMID26796571
Jensen AR
; Doster DL
; Hunsberger EB
; Manning MM
; Stokes SM
; Barwinska D
; March KL
; Yoder MC
; Markel TA
Shock
2016[Jul]; 46
(1
): 75-82
PMID26796571
show ga
OBJECTIVE: Intestinal ischemia can quickly escalate to bowel necrosis and
perforation. Transplantation of stem cells presents a novel treatment modality
for this problem. We hypothesized that: human adipose-derived stromal cells
(hASCs) would increase survival and mesenteric perfusion to a greater degree
compared with differentiated cellular controls following ischemic intestinal
injury, and improved outcomes with hASC therapy would be associated with
preservation of intestinal histological and tight junction architecture, and
lower levels of systemic inflammation following intestinal injury. METHODS: hASCs
and keratinocytes (differentiated cellular control) were cultured on polystyrene
flasks at 37°C in 5% CO2 in air. Adult male C57Bl6J mice were anesthetized and a
midline laparotomy performed. The intestines were eviscerated, the small bowel
mesenteric root identified, and intestinal ischemia was established by
temporarily occluding the superior mesenteric artery for 60?min with a
noncrushing vascular clamp. Following ischemia, the clamp was removed, and the
intestines were returned to the abdominal cavity. Before abdominal closure, 2
million hASCs or keratinocytes in 250??L of phosphate-buffered saline (carrier
for cells and control solution) were infused into the peritoneum. Animals were
allowed to recover for 12 or 24?h (perfusion, histology, cytokine, and
immunofluoresence studies), or 7 days (survival studies). Intestinal perfusion
was assessed by laser Doppler imaging. Intestinal tissue segments were stained
with hematoxylin and eosin, as well as antibodies for the tight junction protein
claudin-1. Separate aliquots of intestine, liver, and lung tissue were
homogenized and assessed for inflammatory cytokines via multiplex beaded assay.
RESULTS: Animals administered hASCs following intestinal ischemia and reperfusion
(I/R) injury had significantly greater 7-day survival and better postischemic
recovery of mesenteric perfusion compared with vehicle or keratinocyte therapy.
hASCs also abated intestinal mucosal destruction, facilitated preservation of
intestinal tight junctions, and decreased the systemic inflammatory response to
injury. CONCLUSIONS: Human adipose-derived stromal cells improved survival and
mesenteric perfusion and attenuated the mucosal damage associated with intestinal
I/R injury. hASCs should be considered as a plausible cell source for novel
cellular treatment plans following intestinal ischemia.