Editorials
Stem Cells Bond Our Organs/Tissues and Engineering Products
2014 Volume 78 Issue 7 Pages 1582-1583
Details
2014 Volume 78 Issue 7 Pages 1582-1583
The human body is made up of trillions of cells that work together. Cells make up tissues and organs, and a group of organs performs a certain function for homeostatic maintenance. Many diseases result from a homeostatic imbalance. Stem cells in organs and/or tissues play important roles in the regulation of homeostasis. Stem cell-based therapy has become a promising strategy for the treatment of many diseases. Therefore, regenerative medicine may one day restore the function of damaged organs or tissues. On the other hand, tissue engineering, such as cell-sheet and artificial organs that might supplement or completely replace the functions of impaired or damaged tissues, has developed remarkably.1 An integrated strategy of tissue engineering including artificial organs and stem cell-based therapy medicine should give rise to a new regenerative medicine for organ failure.
Article p1762
Stents have been used for the treatment of coronary artery disease (CAD) for more than a decade. A coronary stent is placed in an artery to keep the vessel patent to maintain blood flow. Stent implantation is a major treatment option for CAD (eg, in bypass surgery) and has saved many patients’ lives.
But no therapy is without risk. In fact, in clinical practice, persistent inflammation occurs around the stent, and can result in coronary restenosis and thrombosis. Until now, however, there has not been an appropriate experimental in vivo model to analyze the mechanisms of these side effects.
In this issue of the Journal, Sato et al2 report on the established animal models of coronary stenting. In the past, many researchers used the endothelial injury model of CAD, in which there is transient injury to the endothelium, and then the mechanisms of restenosis of the artery are analyzed. But the stent implantation model has had difficulties because of inflammation around the stent. Sato et al used the stenting model of the rat abdominal aorta and showed that transplantation of adipose tissue-derived stem cells (ASCs) prevents this persistent inflammation.
Stem cells can self-renew and differentiate into multiple types of cells and have varying degrees of differentiation potential: pluripotency, ES cells and iPS cells; multipotency, somatic stem cells; and unipotency, or precursor cells. Mesenchymal stem cells (MSCs) are multipotent cells that can be derived from a variety of fetal and adult tissues such as bone marrow and adipose, and possess an immunosuppressive effect.3 Therefore, MSCs are being used in clinical studies of a variety of diseases, and can be used in allogeneic settings without immunosuppressive therapy, and as cellular immunosuppressants that have the potential to control steroid-refractory acute graft vs. host disease.4 In addition, the results of Sato et al suggest that the immunosuppressive effect of MSCs enables construction of a model to analyze the in vivo risk of stent therapy. The authors also show that transplantation of ASCs stimulates reendothelialization and inhibits neointimal formation after stent implantation in the animal model (Figure). They have previously reported that ASCs stimulate reendothelialization and inhibit neointimal formation in a wire injury model.5 In the current experiment, they reproduced the effect of reendothelialization by ASC stimulation in the stent model and used 2 types of stents: a Driver coronary stent (bare metal) and a Cipher stent (sirolimus-eluting). Treatment with the Driver implant resulted in more effective reendothelialization by ASC stimulation than with the Cipher stent.
In stent implantation, administration of mesenchymal stem cells significantly stimulates reendothelialization through paracrine and autocrine effects on cell migration, proliferation, differentiation and cell fusion, leading to tissue/organ regeneration.
MSCs produce and secrete a broad variety of cytokines, chemokines, and growth factors, which influence the microenvironment through paracrine and autocrine effects on cell migration, proliferation, differentiation and cell fusion (Figure).6,7 In fact, these factors are potentially involved in cardiac repair. The implantation of a cell-sheet over the damaged area of a failing heart has been shown to improve cardiac function through a paracrine effect.8 Cell-sheets have recently been developed as a tissue engineering technology, and then put to practical use in several clinical studies. Paracrine effects of the cell-sheets by myoblasts, MSCs and cardiac progenitor cells improve cardiac function.9 Major components of the regenerative mechanism in cell-sheet implantation would be both angiogenesis and the recovery of diastolic function in the heart. Most likely, MSC-released factors lead to tissue/organ remodeling, repair and regeneration in vivo. With stent implantation, MSC administration significantly stimulates reendothelialization and inhibits neointimal formation through paracrine factors.
Sato et al caution that the effect of reendothelialization might depend on the material type of the stent. In the future, factors affecting coronary restenosis after stent deployment in the coronary artery need to be identified. Peripheral technologies have indeed been developing along with the progress of regenerative medicine research, and development of stent design and efficiency and the safety of stent therapy should be expected in the form of combination products with cell-based products.
Cardiovascular disease is a growing problem in our aging society. It will be more important than ever to use stents as treatment for CAD. There are several animal disease models for hypertension, obesity and diabetes, and researchers will use these animals to study the mechanisms of heart disease and the development of stent therapy. The report by Sato et al therefore contributes to the growing number of clinical and preclinical studies of effective stent therapies for heart disease.
None declared.
