Topical Application of Mesenchymal Stromal Cells Ameliorated Liver Parenchyma Damage After Ischemia-Reperfusion Injury in an Animal Model

Lam, P. M.; Chong, Charing Ching‐Ning; Lo, Anthony W.I.; Chan, Anthony W.H.; Tong, Cindy S.W.; Chin, Don Wai Ching; Wong, Kenneth H.; Choy, Richard; Fung, A.; Wáng, Yì Xiáng J.; To, Ka Fai; Lai, Paul Bo San

doi:10.1097/txd.0000000000000675

Cited by 5 publications

(4 citation statements)

References 28 publications

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“…ADMSCs decreased the apoptosis of hepatocytes, decreased the levels of ALT, AST, TBIL, IL-2, and IL-10, and maintained the tissue structure in rats with OLT via alleviation of acute rejection [90]. ADMSCs improved the survival rate of rats with liver IRI by downregulating IL-6, IL-21, and CD70 and activating the neurogenic locus Notch homolog protein pathway; the necrotic areas showed improved liver function and improved liver regeneration and maintained normal histology [91, 92]. Intrahepatic transplantation of ADMSCs markedly reduced the apoptosis of hepatocytes and decreased the severity of pathological changes via downregulation of Fas, Fas ligand, caspase-3, caspase-8, and caspase-9 and upregulation of the Bcl-2/Bax ratio in pigs with IR combined with laparoscopic hepatectomy [93].…”

Section: Introductionmentioning

confidence: 99%

Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases

Zhao

2019

Stem Cell Res Ther

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The liver, the largest organ with multiple synthetic and secretory functions in mammals, consists of hepatocytes, cholangiocytes, hepatic stellate cells (HSCs), sinusoidal endothelial cells, Kupffer cells (KCs), and immune cells, among others. Various causative factors, including viral infection, toxins, autoimmune defects, and genetic disorders, can impair liver function and result in chronic liver disease or acute liver failure. Mesenchymal stem cells (MSCs) from various tissues have emerged as a potential candidate for cell transplantation to promote liver regeneration. Adipose-derived MSCs (ADMSCs) with high multi-lineage potential and self-renewal capacity have attracted great attention as a promising means of liver regeneration. The abundance source and minimally invasive procedure required to obtain ADMSCs makes them superior to bone marrow-derived MSCs (BMMSCs). In this review, we comprehensively analyze landmark studies that address the isolation, proliferation, and hepatogenic differentiation of ADMSCs and summarize the therapeutic effects of ADMSCs in animal models of liver diseases. We also discuss key points related to improving the hepatic differentiation of ADMSCs via exposure of the cells to cytokines and growth factors (GFs), extracellular matrix (ECM), and various physical parameters in in vitro culture. The optimization of culturing methods and of the transplantation route will contribute to the further application of ADMSCs in liver regeneration and help improve the survival rate of patients with liver diseases. To this end, ADMSCs provide a potential strategy in the field of liver regeneration for treating acute or chronic liver injury, thus ensuring the availability of ADMSCs for research, trial, and clinical applications in various liver diseases in the future.

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Section: Introductionmentioning

confidence: 99%

Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases

Zhao

2019

Stem Cell Res Ther

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“…Mesenchymal stromal cells (MSCs) have been extensively investigated for their therapeutic properties after ischemic injury via paracrine/endocrine mechanisms [19,20]. Exosomes (Exos) derived from MSCs have been described as a novel pathway of cell-to-cell interaction and a crucial point in signal regulation [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

Jiang

Wang

Jin

et al. 2018

Cell Physiol Biochem

253

191

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Background/Aims: Recent studies have indicated that exosomes secreted from adipose-derived stem cells (ADSCs) have important effects in the treatment of ischemic injury. However, the treatment mechanism is unclear. This study aimed to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-30d-5p have a protective effect on acute ischemic stroke (AIS). Methods: In the current study, inflammatory factors and miR-30d-5p expression were assessed in 70 subjects with AIS and 35 healthy controls. Exosomes were characterized by transmission electron microscopy and further examined using nanoparticle tracking analyses. A rat model of AIS and an in vitro model of oxygen- and glucose-deprived (OGD) primary microglia were established to study the protective mechanism of exosomes from miR-30d-5p-overexpressing ADSCs in ischemia-induced nerve injury. Results: The results showed that following AIS, the expression of inflammatory cytokines increased, while the anti-inflammatory cytokines IL-4, IL-10, and miR-30d-5p decreased both in patients and in animal models. Moreover, in vitro studies demonstrated that suppression of autophagy significantly reduced the OGD-induced inflammatory response. In addition, exosome treatment was more effective in suppressing the inflammatory response by reversing OGD-induced and autophagy-mediated microglial polarization to M1. Furthermore, in vivo studies showed that exosomes derived from ADSCs significantly decreased the cerebral injury area of infarction by suppressing autophagy and promoting M2 microglia/macrophage polarization. Conclusions: Our results suggest that miR-30d-5p-enhanced ADSC-derived exosomes prevent cerebral injury by inhibiting autophagy-mediated microglial polarization to M1.

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“…The nature of solid organ transplantation, however, may actually allow beneficial flexibility in the choice of administration route since the organs vessels are at least transiently accessible. The topical route of application to the liver in a rat hepatic IRI model was also tested by Lam et al with promising effects [68]. Lastly, the clinical setting of administration may also be important.…”

Section: Discussionmentioning

confidence: 99%

Stem Cells to Modulate IR: a Regenerative Medicine-Based Approach to Organ Preservation

2019

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Purpose of Review Solid organ transplantation is limited by lack of suitable donor organs. Older and comorbid organs are frequently discarded on the basis that they will not withstand the overall process-principally the degree of ischemia reperfusion injury associated with preservation and transplantation. Interventions to prevent injury and promote regeneration are badly needed. Recent stem cells of multiple types including mesenchymal stem cells (MSCs) and adipose-derived regenerative cells (ADRCs) have been demonstrated to protect against tissue injury in multiple models relevant to transplantation. Recent Findings Recent studies have improved our understanding of the multiple mechanisms underlying these beneficial effects including immunomodulatory and anti-inflammatory actions. Evidence suggests extracellular vesicular transfer of therapeutic factors, such as Sox9, cytokines, IL-17A, CCR2, and S1P has a key role in these effects. Summary Several novel approaches such as stress treatments, culture techniques, and exogenous chemical manipulation show significant promise in improving the efficacy of stem cell populations in preventing tissue injury. There is even the possibility to harness the body's own sources of such cells through interventions such as point-of-care fat modulation or mobilization of endogenous bone marrow-derived cells. The many unanswered questions and barriers to translating this promising technology to clinical transplantation are discussed.

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Topical Application of Mesenchymal Stromal Cells Ameliorated Liver Parenchyma Damage After Ischemia-Reperfusion Injury in an Animal Model

Abstract: Supplemental digital content is available in the text.

Cited by 5 publications

References 28 publications

Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases

Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

Stem Cells to Modulate IR: a Regenerative Medicine-Based Approach to Organ Preservation

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