Combinational Therapy of Cardiac Atrial Appendage Stem Cells and Pyridoxamine: The Road to Cardiac Repair?

Lize Evens,Annelies Bronckaers,Maxim Verboven,Dorien Deluyker,Hanne Beliën,Jean-Luc Rummens,Sarah D’Haese,Marc Hendrikx,Sibren Haesen,Virginie Bito

doi:10.3390/ijms22179266

Lize Evens, Annelies Bronckaers + Show 8 more

Open Access

https://doi.org/10.3390/ijms22179266

Copy DOI

Abstract

Myocardial infarction (MI) occurs when the coronary blood supply is interrupted. As a consequence, cardiomyocytes are irreversibly damaged and lost. Unfortunately, current therapies for MI are unable to prevent progression towards heart failure. As the renewal rate of cardiomyocytes is minimal, the optimal treatment should achieve effective cardiac regeneration, possibly with stem cells transplantation. In that context, our research group identified the cardiac atrial appendage stem cells (CASCs) as a new cellular therapy. However, CASCs are transplanted into a hostile environment, with elevated levels of advanced glycation end products (AGEs), which may affect their regenerative potential. In this study, we hypothesize that pyridoxamine (PM), a vitamin B6 derivative, could further enhance the regenerative capacities of CASCs transplanted after MI by reducing AGEs’ formation. Methods and Results: MI was induced in rats by ligation of the left anterior descending artery. Animals were assigned to either no therapy (MI), CASCs transplantation (MI + CASCs), or CASCs transplantation supplemented with PM treatment (MI + CASCs + PM). Four weeks post-surgery, global cardiac function and infarct size were improved upon CASCs transplantation. Interstitial collagen deposition, evaluated on cryosections, was decreased in the MI animals transplanted with CASCs. Contractile properties of resident left ventricular cardiomyocytes were assessed by unloaded cell shortening. CASCs transplantation prevented cardiomyocyte shortening deterioration. Even if PM significantly reduced cardiac levels of AGEs, cardiac outcome was not further improved. Conclusion: Limiting AGEs’ formation with PM during an ischemic injury in vivo did not further enhance the improved cardiac phenotype obtained with CASCs transplantation. Whether AGEs play an important deleterious role in the setting of stem cell therapy after MI warrants further examination.

Highlights

advanced glycation end products (AGEs), we evaluated the effect of cardiac atrial appendage stem cells (CASCs) transplantation
AGEs, we evaluated thefor effect of CASCsoftransplantation products
We have demonstrated in a ratmodel of myocardial infarction (MI) that transplantation of CASCs can prevent worsening of cardiac function after an ischemic injury

Summary

Introduction

Cardiovascular diseases are the leading cause of mortality worldwide, affecting. More than 40% of deaths related to cardiovascular diseases are due to myocardial infarction (MI). MI occurs when the coronary blood supply is interrupted, leading to irreversible loss of cardiomyocytes [2]. Following MI, adverse left ventricular (LV) remodeling often evolves into heart failure [3]. Current therapeutic approaches reduce the risk of recurrent infarctions and improve patient outcome. As lost cardiac tissue is not replaced [4], the progression towards heart failure with current therapies is only delayed, rather than prevented. As the renewal rate of the heart is limited [5], strategies to restore functional cardiac tissue are urgently needed. The ideal therapy should replace necrotic cells while simultaneously restoring the function of viable tissue. A large number of endogenous stem cell types (such as mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), and hematopoietic stem cells (HSCs)) have emerged as potential treatment options for regenerative medicine [6]

Methods

Discussion

Conclusion