Preconditioning of umbilical cord‐derived mesenchymal stem cells by rapamycin increases cell migration and ameliorates liver ischaemia/reperfusion injury in mice via the CXCR4/CXCL12 axis

Zheng, Jun; Li, Hui; He, Lin; Huang, Yiming; Cai, Jianye; Chen, Liang; Zhou, Chaorong; Fu, Hai-Xia; Lu, Tian; Zhang, Yingcai; Yao, Jia; Yang, Yang

doi:10.1111/cpr.12546

Cited by 57 publications

(41 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was noticed that, the induction of autophagy by rapamycin promotes the capability of the MSCs to migrate and express anti-inflammatory cytokines as well as increase the expressions of CXCR4 without affecting cellular viability. Upon in vivo administration of the modified MSCs, more of the cells migrated towards the ischaemic regions through the CXCR4/CXCL12 axis resulting in improved hepatic function and reduced inflammatory cytokines [84]. Again, preconditioning MSCs with deferoxamine, is an efficient way of increasing migration as well as homing [85].…”

Section: Improving Migrationmentioning

confidence: 99%

Improved therapeutics of modified mesenchymal stem cells: an update

Pei²,

et al. 2020

View full text Add to dashboard Cite

Background: Mesenchymal stromal cells (MSCs) have attracted intense interest due to their powerful intrinsic properties of self-regeneration, immunomodulation and multi-potency, as well as being readily available and easy to isolate and culture. Notwithstanding, MSC based therapy suffers reduced efficacy due to several challenges which include unfavorable microenvironmental factors in vitro and in vivo. Body: In the quest to circumvent these challenges, several modification techniques have been applied to the naïve MSC to improve its inherent therapeutic properties. These modification approaches can be broadly divided into two groups to include genetic modification and preconditioning modification (using drugs, growth factors and other molecules). This field has witnessed great progress and continues to gather interest and novelty. We review these innovative approaches in not only maintaining, but also enhancing the inherent biological activities and therapeutics of MSCs with respect to migration, homing to target site, adhesion, survival and reduced premature senescence. We discuss the application of the improved modified MSC in some selected human diseases. Possible ways of yet better enhancing the therapeutic outcome and overcoming challenges of MSC modification in the future are also elaborated. Conclusion: The importance of prosurvival and promigratory abilities of MSCs in their therapeutic applications can never be overemphasized. These abilities are maintained and even further enhanced via MSC modifications against the inhospitable microenvironment during culture and transplantation. This is a turning point in MSC-based therapy with promising preclinical studies and higher future prospect.

show abstract

Section: Improving Migrationmentioning

confidence: 99%

Improved therapeutics of modified mesenchymal stem cells: an update

Pei²,

et al. 2020

View full text Add to dashboard Cite

show abstract

“…They are able to give rise to mesodermal lineages including adipocytes, osteocytes and chondrocytes [10]. Moreover, transplanted MSCs take part in liver regeneration by migrating toward injured tissues, participating in hepatocyte differentiation and paracrine mechanisms and having immunomodulatory properties [11][12][13]. In vitro culture with specific growth factors promoted the hepatogenic differentiation of MSCs into hepatocyte-like cells (HLCs) with liver-specific morphology and liver functions, including abilities to uptake low-density lipoprotein and indocyanine green, secrete albumin and urea, and store glycogen and the cells also had cytochrome P450 activity [14].…”

Section: Ivyspringmentioning

confidence: 99%

Mesenchymal stromal cells promote liver regeneration through regulation of immune cells

Wang

2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

The liver is sensitive to pathogen-induced acute or chronic liver injury, and liver transplantation (LT) is the only effective strategy for end-stage liver diseases. However, the clinical application is limited by a shortage of liver organs, immunological rejection and high cost. Mesenchymal stromal cell (MSC)-based therapy has gradually become a hot topic for promoting liver regeneration and repairing liver injury in various liver diseases, since MSCs are reported to migrate toward injured tissues, undergo hepatogenic differentiation, inhibit inflammatory factor release and enhance the proliferation of liver cells in vivo. MSCs exert immunoregulatory effects through cell-cell contact and the secretion of anti-inflammatory factors to inhibit liver inflammation and promote liver regeneration. In addition, MSCs are reported to effectively inhibit the activation of cells of the innate immune system, including macrophages, natural killer (NK) cells, dendritic cells (DCs), monocytes and other immune cells, and inhibit the activation of cells of the adaptive immune system, including T lymphocytes, B lymphocytes and subsets of T cells or B cells. In the current review, we mainly focus on the potential effects and mechanisms of MSCs in inhibiting the activation of immune cells to attenuate liver injury in models or patients with acute liver failure (ALF), nonalcoholic fatty liver disease (NAFLD), and liver fibrosis and in patients or models after LT. We highlight that MSC transplantation may replace general therapies for eliminating acute or chronic liver injury in the near future.

show abstract

“…these MSCs showed enhanced migration via the CXCR-4/CXCL-12 axis. 56 Pre-treatment with anaesthetics such as dexmedetomidine and midazolam enhanced the efficacy of MSCs by increasing migratory capacity, cytokine secretion (HGF, FGF, vascular endothelial growth factor [VEGF] and insulin-like growth factor 1 [IGF-1]) and NF-κB p65 nuclear translocation to protect LO2 cells from hypoxia-reoxygenation-induced injury. 20 Heat-shock pre-treatment (HSP) significantly attenuated hydrogen peroxide (H 2 O 2 )-induced apoptosis by down-regulating Bax and cytochrome C levels and upregulating Bcl-2 levels and autophagy in MSCs.…”

Section: Tr An S Pl Anted Hlc S With Improved Liver Fun C Ti On Maymentioning

confidence: 99%

Pre‐treatments enhance the therapeutic effects of mesenchymal stem cells in liver diseases

Wang

2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Liver diseases caused by viral infection, alcohol abuse and metabolic disorders can progress to end‐stage liver failure, liver cirrhosis and liver cancer, which are a growing cause of death worldwide. Although liver transplantation and hepatocyte transplantation are useful strategies to promote liver regeneration, they are limited by scarce sources of organs and hepatocytes. Mesenchymal stem cells (MSCs) restore liver injury after hepatogenic differentiation and exert immunomodulatory, anti‐inflammatory, antifibrotic, antioxidative stress and antiapoptotic effects on liver cells in vivo. After isolation and culture in vitro, MSCs are faced with nutrient and oxygen deprivation, and external growth factors maintain MSC capacities for further applications. In addition, MSCs are placed in a harsh microenvironment, and anoikis and inflammation after transplantation in vivo significantly decrease their regenerative capacity. Pre‐treatment with chemical agents, hypoxia, an inflammatory microenvironment and gene modification can protect MSCs against injury, and pre‐treated MSCs show improved hepatogenic differentiation, homing capacity, survival and paracrine effects in vitro and in vivo in regard to attenuating liver injury. In this review, we mainly focus on pre‐treatments and the underlying mechanisms for improving the therapeutic effects of MSCs in various liver diseases. Thus, we provide evidence for the development of MSC‐based cell therapy to prevent acute or chronic liver injury. Mesenchymal stem cells have potential as a therapeutic to prolong the survival of patients with end‐stage liver diseases in the near future.

show abstract

Preconditioning of umbilical cord‐derived mesenchymal stem cells by rapamycin increases cell migration and ameliorates liver ischaemia/reperfusion injury in mice via the CXCR4/CXCL12 axis

Cited by 57 publications

References 62 publications

Improved therapeutics of modified mesenchymal stem cells: an update

Improved therapeutics of modified mesenchymal stem cells: an update

Mesenchymal stromal cells promote liver regeneration through regulation of immune cells

Pre‐treatments enhance the therapeutic effects of mesenchymal stem cells in liver diseases

Contact Info

Product

Resources

About