scholarly journals Donor heart preservation with hypoxic-conditioned medium-derived from bone marrow mesenchymal stem cells improves cardiac function in a heart transplantation model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pengyu Zhou ◽  
Hao Liu ◽  
Ximao Liu ◽  
Xiao Ling ◽  
Zezhou Xiao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Heart Transplantation ◽  
Conditioned Medium ◽  
Donor Heart ◽  
Cardioplegic Solution ◽  
Heart Preservation ◽  
Marrow Mesenchymal Stem Cells ◽  
Antibody Arrays

Abstract Background In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients’ survival rate. Bone marrow mesenchymal stem cells (BMSCs) have been reported to attenuate myocardial I/R injury via their paracrine effects, which can be enhanced by hypoxic preconditioning. We hypothesized that the donor heart preservation with hypoxic conditioned medium (CdM) derived from BMSCs would improve post-transplant graft function. Methods Normoxic or hypoxic CdM were isolated from rat BMSCs cultured under normoxic (20% O2) or hypoxic (1% O2) condition. Donor hearts were explanted; stored in cardioplegic solution supplemented with either a medium (vehicle), normoxic CdM (N-CdM), or hypoxic CdM (H-CdM); and then heterotopically transplanted. Antibody arrays were performed to compare the differences between hypoxic and normoxic CdM. Results After heart transplantation, the donor heart preservation with normoxic CdM was associated with a shorter time to return of spontaneous contraction and left ventricular systolic diameter, lower histopathological scores, higher ejection fraction, and fractional shortening of the transplanted hearts. The cardioprotective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of plasma proinflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CdM group compared with the vehicle group. These therapeutic effects can be further enhanced by hypoxic preconditioning. Antibody arrays revealed that nine proteins were significantly increased in hypoxic CdM compared with normoxic CdM. Furthermore, compared with vehicle and N-CdM groups, the protein levels of PI3K and p-Akt/Akt ratio in the transplanted hearts significantly increased in the H-CdM group. However, no significant difference was found in the phosphorylation of Smad2 and Smad3 for the donor hearts among the three groups. Conclusions Our results indicate that the cardioplegic solution-enriched with hypoxic CdM can be a novel and promising preservation solution for donor hearts.

scholarly journals Donor heart preservation with hypoxic conditioned medium derived from bone marrow mesenchymal stem cell improves cardiac function in a heart transplantation model

2020 ◽  
Author(s):  
Pengyu Zhou ◽  
Hao Liu ◽  
Ximao Liu ◽  
Xiao Ling ◽  
Zezhou Xiao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Heart Transplantation ◽  
Conditioned Medium ◽  
Hypoxic Preconditioning ◽  
Vehicle Group ◽  
Donor Heart ◽  
Cardioplegic Solution ◽  
Heart Preservation ◽  
Antibody Arrays ◽  
Transplanted Hearts

Abstract Background: In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients’ survival rate. Bone marrow mesenchymal stem cells (BMSCs) have been reported to attenuate myocardial I/R injury via their paracrine effects, which can be enhanced by hypoxic preconditioning. We hypothesized that the donor heart preservation with hypoxic conditioned medium (CdM) derived from BMSCs would improve post-transplant graft function. Methods: Normoxic or hypoxic CdM were isolated from rat BMSCs cultured under normoxic (20% O2) or hypoxic (1% O2) condition. Donor hearts were explanted, stored in cardioplegic solution supplemented with either a medium (Vehicle), normoxic CdM (N-CdM), or hypoxic CdM (H-CdM), and then heterotopically transplanted. Antibody arrays were performed to compare the differences between hypoxic and normoxic CdM.Results: After heart transplantation, the donor heart preservation with normoxic CdM was associated with a shorter time to return of spontaneous contraction and left ventricular systolic diameter, lower histopathological scores, higher ejection fraction, and fractional shortening of transplanted hearts. The cardioprotective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of plasma proinflammatory cytokines (Interleukin-1β, Interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CdM group compared with the vehicle group. These therapeutic effects can be further enhanced by hypoxic preconditioning. Antibody arrays revealed that nine proteins were significantly increased in hypoxic CdM compared with normoxic CdM. Furthermore, compared with vehicle and N-CdM groups, the protein levels of PI3K and p‐Akt/Akt ratio in the transplanted hearts significantly increased in the H-CdM group. However, no significant difference was found in the phosphorylation of Smad2 and Smad3 for the donor hearts among the three groups. Conclusions: Our results indicate that the cardioplegic solution-enriched with hypoxic CdM can be a novel and promising preservation solution for donor hearts.

scholarly journals Donor Heart Preservation with Hypoxic Conditioned Medium Derived from Bone Marrow Mesenchymal Stem cell improves Cardiac Function in a Heart Transplantation Model

2020 ◽  
Author(s):  
Pengyu Zhou ◽  
Hao Liu ◽  
Ximao Liu ◽  
Xiao Ling ◽  
Zezhou Xiao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Heart Transplantation ◽  
Conditioned Medium ◽  
Hypoxic Preconditioning ◽  
Vehicle Group ◽  
Donor Heart ◽  
Cardioplegic Solution ◽  
Heart Preservation ◽  
Antibody Arrays ◽  
Transplanted Hearts

Abstract Background: In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients’ survival rate. Bone marrow mesenchymal stem cells (BMSCs) have been reported to attenuate myocardial I/R injury via their paracrine effects, which can be enhanced by hypoxic preconditioning. We hypothesized that the donor heart preservation with hypoxic conditioned medium derived from BMSCs (CM-BMSCs) would improve post-transplant graft function. Methods: Normoxic CM and hypoxic CM were isolated from rat BMSCs cultured under normoxic (20% O2) or hypoxic (1% O2) condition. Donor hearts were explanted, stored in cardioplegic solution supplemented with either a medium (Vehicle), normoxic CM (N-CM), or hypoxic CM (H-CM), and then heterotopically transplanted. Antibody arrays were performed to compare the differences between hypoxic CM and normoxic CM.Results: After heart transplantation, the donor heart preservation with normoxic CM was associated with shorter re-beating time, histopathological scores, and left ventricular systolic diameter, higher ejection fraction, and fractional shortening of transplanted hearts. These protective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of serum proinflammatory cytokines (Interleukin-1β, Interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CM group compared with the vehicle group. These therapeutic effects can be further enhanced by hypoxic preconditioning. Antibody arrays revealed that nine proteins were significantly increased in hypoxic CM compared with normoxic CM. Furthermore, compared with vehicle and N-CM groups, the protein levels of PI3K and p‐Akt/Akt ratio in the transplanted hearts significantly increased in the H-CM group. Conclusions: Our results indicate that cardioplegic solution-enriched with hypoxic CM-BMSCs can be a novel and promising preservation solution for donor hearts.

Conditioned medium enhances the fusion capability of rat bone marrow mesenchymal stem cells and cardiomyocytes

2014 ◽  
Vol 41 (5) ◽  
pp. 3099-3112 ◽  
Author(s):  
Kanwal Haneef ◽  
Nadia Naeem ◽  
Irfan Khan ◽  
Hana’a Iqbal ◽  
Nurul Kabir ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Marrow Mesenchymal Stem Cells ◽  
Rat Bone

scholarly journals Differentiation of Bone Marrow Mesenchymal Stem Cells into Neural Lineage Cells Induced by bFGF-Chitosan Controlled Release System

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Manli Li ◽  
Wen Zhao ◽  
Yudan Gao ◽  
Peng Hao ◽  
Junkui Shang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Controlled Release ◽  
Conditioned Medium ◽  
Serum Starvation ◽  
Neural Lineage ◽  
Release System ◽  
Marrow Mesenchymal Stem Cells ◽  
Controlled Release System

Bone marrow mesenchymal stem cells undergo differentiation to different lineages with different efficiencies when induced by different factors. We added a bFGF-chitosan controlled release system (bFGF-CCRS) as an inducer into conditioned medium to facilitate the oriented differentiation of BMSCs into neural lineage cells (eventually mature neurons); furthermore, we synchronized BMSCs to the G0/G1 phase via serum starvation to observe the effect of the inducer on the differentiation direction and efficiency. The nonsynchronized group, chitosan alone (not loaded with bFGF) group, soluble bFGF group, and conditioned medium group served as controls, and we observed the dynamic process of differentiation of BMSCs into neural lineage cells at different time points after the beginning of coculture. We analyzed the binding patterns of bFGF and chitosan and assayed the expression differences of key factors (FGFR1, ERK, and c-fos) and molecular switches (BTG2) that regulate the transformation from cell proliferation to differentiation. We also investigated the potential molecular mechanism of BMSC differentiation into neural lineage cells at a high percentage when induced by bFGF-CCRS.

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