Human umbilical cord mesenchymal stem cells protect against ischemic brain injury in mouse by regulating peripheral immunoinflammation

Cheng, Qingqing; Zhang, Zhuo; Zhang, Shenyang; Yang, Hui; Zhang, Xin; Pan, Jie; Weng, Leihua; Sha, Dujuan; Zhu, Min; Hu, Xiang; Xu, Yun

doi:10.1016/j.brainres.2014.10.065

Cited by 55 publications

(39 citation statements)

References 49 publications

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“…Bone marrow-derived MSCs are able to induce Tregs from peripheral blood mononuclear cells [27,28]. Recently, hUC-MSCs exhibited suppressive effects on peripheral immune inflammation [29]. These data suggest hUC-MSCs can induce Tregs, and indoxyl sulfate can inhibit this process.…”

Section: Effects Of Indoxyl Sulfate On the Huc-mscs-induced Generatiomentioning

confidence: 95%

The Effects of Indoxyl Sulfate on Human Umbilical Cord-Derived Mesenchymal Stem Cells In Vitro

Liu

Wang

et al. 2016

Cell Physiol Biochem

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Background/Aims: Indoxyl sulfate, an important protein-bound uremic toxin, can damage stem cells, thus hampering stem cell-based regenerative medicine approaches targeting chronic kidney diseases (CKD). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are thought to have promising clinical application because of their high proliferative potential and ease of isolation than MSCs from other sources. In the present study, we aimed to determine the harmful effects of indoxyl sulfate on the phenotype and functional potential of hUC-MSCs in vitro. Methods: The toxicity and cell viability was examined by Trypan blue exclusion and MTT assay. The cellular surface markers and the percentage of apoptotic cells by Annexin-V/PI staining were analyzed by flow cytometry. Proliferation was evaluated based on cell number counting and Ki-67 immunostaining. Cell senescence was measured using senescence-associated β-Galactosidase activity. The ability to stimulate the development of CD4⁺CD25⁺FoxP3⁺ regulatory T cells was assessed by incubating hUC-MSCs with peripheral blood mononuclear cells from the healthy volunteers. Results: Our results demonstrated that the immunophenotype of hUC-MSCs was not affected by indoxyl sulfate flow cytometry. However, a significant decrease in cell numbers and fraction of Ki-67 positive proliferating cells, along with a significant increase in cellular senescence were detected in hUC-MSCs after exposure to indoxyl sulfate. Additionally, their ability to stimulate CD4⁺CD25⁺FoxP3⁺ regulatory T cell production was compromised when hUC-MSCs were pretreated with indoxyl sulfate. Conclusion: Taken together, our study clearly demonstrated that the molecular alterations and functional incompetence in hUC-MSCs under the challenge of indoxyl sulfate in vitro.

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Section: Effects Of Indoxyl Sulfate On the Huc-mscs-induced Generatiomentioning

confidence: 95%

The Effects of Indoxyl Sulfate on Human Umbilical Cord-Derived Mesenchymal Stem Cells In Vitro

Liu

Wang

et al. 2016

Cell Physiol Biochem

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“…A variety of preclinical studies have shown potential therapeutic value of stem cell populations derived from human umbilical CB in limiting injury and in promoting functional recovery. In rodent stroke models, the administration of neural stem cells lead to glial and neuronal differentiation at sites of injury, while transplanted MSCs were indirectly beneficial by inducing the release of neuroprotective trophic factors that dampened inflammation 95;96 . Human CB-derived AC133+ EPCs limited infarct size and shortened the resolution period in a rat stroke model 97 .…”

Section: Stem Cells For the Treatment Of Post-insult Injury In Neonatesmentioning

confidence: 99%

“…The “new” BPD is associated with lung growth arrest as well as abnormal vascularization and fibrosis, and it can result in disabling lung abnormalities that persist into adulthood 79 . Studies in neonatal animal models of BPD have shown that transplantation with MSC or soluble MSC-derived proteins (the MSC “secretome”) can modulate BPD by dampening inflammatory processes 96;103–105 . In a recently reported phase I dose-escalation trial, a small group of extremely preterm infants who received intra-tracheal autologous MSC had diminished BPD severity and lowered inflammatory cytokine levels in tracheal aspirates compared to historical controls 106 .…”

Section: Stem Cells For the Treatment Of Post-insult Injury In Neonatesmentioning

confidence: 99%

“…Mesenchymal stem cells (MSC) derived from developing humans exhibit a high degree of mesodermal pluripotency (the capacity to differentiate into multiple cell types); in addition, these MSC are associated with a low induction of immune responses in the recipient and exhibit anti-inflammatory properties 96;113 . Another type of cell with pluripotent properties is the hAEC 114 .…”

Section: Utility Of Neonatal Sct: General Considerationsmentioning

confidence: 99%

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Stem Cells

Yoshimoto

Koenig

2015

Clinics in Perinatology

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Synopsis Stem cell transplantation (SCT) is an established first-line or adjunctive therapy for a variety of neonatal and adult diseases. New evidence in preclinical models as well as a small number of human studies show the potential utility of SCT in neuroprotection and in the modulation of inflammatory injury in at risk-neonates. In this review we briefly summarize current understanding of human stem cell biology during ontogeny and present recent evidence supporting SCT as a viable approach for post-insult neonatal injury.

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“…This study proved that MSC transplantation could ameliorate PA metabolic dysfunction in ischemic brain injuries. 17 Cheng et al 18 demonstrated that human bone marrowderived MSC treatment via tail vein injection within 30 minutes after stroke ameliorated neurological deficit, brain edema, and infarct volume via a mechanism involving increasing TGF-β level modulating peripheral immunoinflammation. Previous studies also observed that MSCs reduce the brain water content and protect BBB integrity following cerebral ischemia.…”

Section: Introductionmentioning

confidence: 99%