scholarly journals Precise Regulation of miR-210 is Critical for the Cellular Homeostasis Maintenance and Transplantation Efficacy Enhancement of Mesenchymal Stem Cells in Acute Liver Failure Therapy

2017 ◽  
Vol 26 (5) ◽  
pp. 805-820 ◽  
Author(s):  
Yingxia Liu ◽  
Yongjia Xiong ◽  
Feiyue Xing ◽  
Hao Gao ◽  
Xiaogang Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Cell Survival ◽  
Cell Transplantation ◽  
Survival Ratio ◽  
Ros Production

Stem cell transplantation is a promising clinical strategy to cure acute liver failure. However, a low cell survival ratio after transplantation significantly impairs its therapeutic efficacy. This is partly due to insufficient resistance of transplanted stem cells to severe oxidative and inflammatory stress at the injury sites. In the current study, we demonstrated that a small molecule zeaxanthin dipalmitate (ZD) could enhance the defensive abilities against adverse stresses of human adipose-derived mesenchymal stem cells (hADMSCs) in vitro and increase their therapeutic outcomes of acute liver failure after transplantation in vivo. Treatment with ZD dramatically improved cell survival and suppressed apoptosis, inflammation, and reactive oxygen species (ROS) production of hADMSCs through the PKC/Raf-1/MAPK/NF-κB pathway to maintain a reasonably high expression level of microRNA-210 (miR-210). The regulation loop between miR-210 and cellular/mitochondrial ROS production was found to be linked by the ROS inhibitor iron–sulfur cluster assembly proteins (ISCU). Pretreatment with ZD and stable knockdown of miR-210 significantly improved and impaired the stem cell transplantation efficacy through the alteration of hepatic cell expansion and injury amelioration, respectively. Vehicle treatment with ZD did not pose any adverse effect on cell homeostasis or healthy animal. In conclusion, elevating endogenous antioxidant level of hADMSCs with ZD significantly enhances their hepatic tissue-repairing capabilities. Maintenance of a physiological level of miR-210 is critical for hADMSC homeostasis.

Unmanipulated HLA Haploidentical Bone Marrow Transplantation Combined With PBSC With The Options Of Donor Virus Specific CTLs and Mesenchymal Stem Cells Infusion

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3262-3262
Author(s):  
Yoshiyuki Takahashi ◽  
Nozomu Kawashima ◽  
Atsushi Narita ◽  
Hirotoshi Sakaguchi ◽  
Hideki Muramatsu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Virus Infections ◽  
Specific Ctls ◽  
Donor Bone Marrow ◽  
Steroid Refractory

Abstract Introduction HLA haploidentical relatives could be useful alternative donor option for patients without HLA matched family donor who need relatively urgent stem cell transplantation. However, steroid refractory GVHD and virus infections were critical issues in this setting due to HLA mismatched barrier. Donor derived cellular therapies could be suitable options to improve the outcome of this strategy. Patients and methods Twenty three children (9 male, 14 female) underwent HLA haploidentical stem cell transplantation in Nagoya University hospital from 2004 to 2013. The median age was 8 years [range 1 – 15years] with 7 AML, 6 ALL, 5 aplastic anemia, 2 JMML, 1 CMML, 1 CAEBV and 1 LCH. All the patients received both bone marrow combined with G-CSF mobilized peripheral blood stem cells to increase the number of infused donor stem cells. Total 15mg /kg of rabbit antithymocyte globulin (ATG) were given as in vivo T cell depletion in preconditioning regimen. Taclolimus and short term MTX were used for GVHD prophylaxis. CMV and EBV specific cytotoxic T cells were tried to expand from donor peripheral blood mononuclear cells if the patient and the donor shared either HLA A2402 or A0201/A0206 as treatment options for drug resistant virus infections since 2008. Mesenchymal stem cells were also expanded from donor bone marrow for the option of treatment for steroid refractory GVHD since 2009. All the donors were one of parents of patient’s except for one brother. HLA disparity between patient and donor at HLA A, B, and DR loci were three loci in 12 patients and two loci were in other 11 patients. Results All the patients achieved engraftment with median 18 days [range 14 – 29 days]. Acute GVHD grade II or more were seen in nine patients. Six of them developed steroid refractory GVHD and received Infliximab. Four of them received Daclizumab as well. Among them, two patients developed uncontrolled grade IV GVHD (One patient developed diarrhea more than three litters with blood and another patient developed Grade IV liver GVHD) even after combination therapy of Infliximab and Daclizumab. Two infusions of donor bone marrow derived MSC were given in these two patients and GVHD were diminished. CMV reactivations were seen in 16 and 3 of them developed both GCV and Foscanet resistant CMV infection and donor derived CMV specific CTL infusions were effective to eradicate CMV-DNA in their blood without inducing GVHD. EBV reactivations were seen in 12 and empiric rituximab infusion was effective in 11. One patient developed CD20 negative EBV associated lymphoproliferative disorder and 5 course of donor derived EBV specific T cell infusions eradicate EBV-DNA in his blood and PET positive lymphadenopathy was diminished. BK virus cystitis were seen in four. Cause of death were 8 leukemia relapses, one adenovirus fluminant hepatitis on day 123, one CMV ventriculitis on day 378 and one sepsis on day 509. Conclusions Donor virus specific CTLs and mesenchymal stem cells were useful options for HLA haploidentical stem cell transplantation to reduce early transplantation related mortality. Disclosures: No relevant conflicts of interest to declare.

Host Origin of Marrow Mesenchymal Stem Cells Following Allogeneic Cord-Blood Stem-Cell Transplantation

2001 ◽  
Vol 74 (2) ◽  
pp. 235-236 ◽  
Author(s):  
Suradej Hongeng ◽  
Sawang Petvises ◽  
Budsaba Rerkamnuaychoke ◽  
Surapon Worapongpaiboon ◽  
Pimpan Tardtong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Cord Blood Stem Cell ◽  
Marrow Mesenchymal Stem Cells ◽  
Host Origin ◽  
Blood Stem Cell Transplantation
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