Secretome from human adipose-derived stem cells protects mouse liver from hepatic ischemia–reperfusion injury

Lee, Sang Chul; Kim, Jong Ok; Kim, Say-June

doi:10.1016/j.surg.2014.12.016

Cited by 33 publications

(30 citation statements)

References 45 publications

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“…While previous studies have demonstrated the therapeutic benefits of hASCs in attenuation of other animal models of I/R injury [21], this is the first study to demonstrate the efficacy of human ASCs in rescuing murine intestinal ischemia. Previous studies have suggested that ASCs provide their benefit at least in part, by the release of paracrine factors [22, 23].…”

Section: Discussionmentioning

confidence: 94%

Human Adipose Stromal Cells Increase Survival and Mesenteric Perfusion Following Intestinal Ischemia and Reperfusion Injury

Jensen

Doster

Hunsberger

et al. 2016

Shock

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Background 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: (1) Human adipose derived stromal cells (hASCs) would increase survival and mesenteric perfusion to a greater degree compared to differentiated cellular controls following ischemic intestinal injury, (2) 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 37C 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 minutes with a non-crushing vascular clamp. Following ischemia, the clamp was removed and the intestines were returned to the abdominal cavity. Prior to abdominal closure, two million hASCs or keratinocytes in 250 uL of PBS (carrier for cells and control solution) were infused into the peritoneum. Animals were allowed to recover for 12 or 24 hours (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 H&E, 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 injury (I/R) had significantly greater 7 day survival and better post-ischemic recovery of mesenteric perfusion compared to vehicle or keratinocyte therapy. hASCs also abated intestinal mucosal destruction, facilitated preservation of intestinal tight junctions, and decreased the systemic inflammatory response to injury. Conclusion Human adipose derived stromal cells improved survival and mesenteric perfusion and attenuated the mucosal damage associated with intestinal ischemia and reperfusion injury. hASCs should be considered as a plausible cell source for novel cellular treatment plans following intestinal ischemia.

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Section: Discussionmentioning

confidence: 94%

Human Adipose Stromal Cells Increase Survival and Mesenteric Perfusion Following Intestinal Ischemia and Reperfusion Injury

Jensen

Doster

Hunsberger

et al. 2016

Shock

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“…In humans, the MSCs secretome consists of over 100 biologically active molecules including different types of cytokines, chemokines, and growth factors [48]. In different pathologies such as acute myocardial infarction and brain or liver damage, it has been shown that the administration of the MSC secretome is able to reproduce, at least in part, the therapeutic effect observed after the administration of living cells [49, 50] while at the same time reducing the therapy complexity and the cost. However, a major issue associated with the use of MSC secretome is that in most cases the concentration of cytokines and growth factors are too low for therapeutic use [51].…”

Section: Discussionmentioning

confidence: 99%

Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy

et al. 2017

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Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when evaluated in an in vitro model of DN. Altogether, our findings suggest that DFX preconditioning of AD-MSCs improves their therapeutic potential and should be considered as a potential strategy for the generation of new alternatives for DN treatment.

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“…The presence of VEGF, bFGF, TGF-β1, TGF-β2, HGF, keratinocyte growth factor (KGF), PDGF-AA, placenta growth factor (PGF), type I collagen, fibronectin, and superoxide dismutase (SOD) in ASCs seretome was effective in improving skin texture and wrinkle in micro pig model [218]. In addition, another study evaluated the potential of secretome (concentrated ASCs-CM) in controlling ischemia reperfusion (IR) injury in mice model indicating the potential ASC-secretome in providing therapeutic option for treatment of IR injury [219]. The ASCs–CM has also recovered gastric wound in rat model through promoting angiogenesis and re-epithelization [220].…”

Section: Asc Secretome and Its Therapeutic Effectmentioning

confidence: 99%

Revisiting the Advances in Isolation, Characterization and Secretome of Adipose-Derived Stromal/Stem Cells

Dubey

Mishra²,

Dubey

et al. 2018

IJMS

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Adipose-derived stromal/stem cells (ASCs) seems to be a promising regenerative therapeutic agent due to the minimally invasive approach of their harvest and multi-lineage differentiation potential. The harvested adipose tissues are further digested to extract stromal vascular fraction (SVF), which is cultured, and the anchorage-dependent cells are isolated in order to characterize their stemness, surface markers, and multi-differentiation potential. The differentiation potential of ASCs is directed through manipulating culture medium composition with an introduction of growth factors to obtain the desired cell type. ASCs have been widely studied for its regenerative therapeutic solution to neurologic, skin, wound, muscle, bone, and other disorders. These therapeutic outcomes of ASCs are achieved possibly via autocrine and paracrine effects of their secretome comprising of cytokines, extracellular proteins and RNAs. Therefore, secretome-derivatives might offer huge advantages over cells through their synthesis and storage for long-term use. When considering the therapeutic significance and future prospects of ASCs, this review summarizes the recent developments made in harvesting, isolation, and characterization. Furthermore, this article also provides a deeper insight into secretome of ASCs mediating regenerative efficacy.

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Secretome from human adipose-derived stem cells protects mouse liver from hepatic ischemia–reperfusion injury

Cited by 33 publications

References 45 publications

Human Adipose Stromal Cells Increase Survival and Mesenteric Perfusion Following Intestinal Ischemia and Reperfusion Injury

Human Adipose Stromal Cells Increase Survival and Mesenteric Perfusion Following Intestinal Ischemia and Reperfusion Injury

Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy

Revisiting the Advances in Isolation, Characterization and Secretome of Adipose-Derived Stromal/Stem Cells

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