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Pluripotent stem cells offer tremendous potential for the treatment of various diseases, including cardiovascular disease. Myocardial infarction results in the almost irreversible loss of over 1 billion cardiomyocytes, with little endogenous replacement from the damaged heart. Subsequently, the quality of life of patients recovering from myocardial infarction is significantly reduced and is, to date, without an effective cure. Pluripotent stem cell-derived cardiomyocytes bring exciting potential for use in regenerative medicine therapies by replacing the damaged cells with healthy, lab-grown cardiomyocytes. However, safety concerns regarding the purity and maturity of pluripotent stem cell-derived heart muscle is currently still a significant barrier to the successful translation of lab-grown cells into patients. This chapter will review the current status of embryonic and induced pluripotent stem cell strategies to generate heart muscle, as well as discuss the currently remaining obstacles which must be overcome for the safe clinical application of stem cell therapy.

In spite of the current notable advances in surgical management of critical limb ischemia (CLI), the most severe form of peripheral artery disease, it is still associated with the high frequency of amputations, lethality and low quality of life. Although the compensatory opportunities are mainly exhausted in the treatment of CLI, an efficient medical intervention remains possible. The purpose of this intervention is to eliminate a pronounced imbalance between the blood supply of the ischemic tissues and their metabolic needs. The physiological compensatory arteriogenesis, which actively proceeds at the initial stages of limb ischemia, almost ceases to the beginning of its transition into the final stages. Therefore, research efforts are focused on those technologies for tissue repair which are directed at the activation and expansion of the microvascular bed (angiogenesis) in the affected limb. Cell therapy, having been actively studied from the beginning of 2000s, is one of such approaches. This review discusses in-depth the advantages of different cell types for the CLI therapy, including peripheral bone marrow-derived mononuclear cells (BMMNCs) and mesenchymal stem cells (BMMSCs). The results of the most important pre-clinical and clinical studies, including the ongoing clinical trials, involving cell-based approach for CLI therapy have also been discussed besides optimization of the cell delivery techniques with or without the use of biomaterials as cell carriers.

Heart disease is the primary cause of mortality and morbidity in the world. Existing therapies limit the extent of injury without structural restoration of the lost myocardial tissue. Consequently, injured myocardial tissue continues to remodel that ultimately leads to cardiac failure. Cell therapy provides a promising alternative for enhancement of cardiac structure and function, yet the mechanism explaining salutary effects remain elusive. Ability of the transplanted stem cells to adopt cardiac cell morphology dubbed as the “Transdifferentiation Hypothesis” is widely believed to be the mechanism for cell therapy. Recently, however multiple studies provide evidence that challenges the transdifferentiation hypothesis, thereby questioning the ability of transplanted stem cells to differentiate into tissue cell types. Alternatively, stem cells secrete growth factors, proteins and extracellular vesicles including exosomes that possess cardioprotective and regenerative properties, thereby forming the “Paracrine Hypothesis”. This chapter aims to summarize the cell therapy and its applications for cardiac repair and regeneration including mechanisms explaining beneficial effect of the transplanted stem cells. A particular focus will be on the emerging importance of the paracrine hypothesis and its future implication for cardiac tissue repair after injury.

Recent years have observed the development of stem cell therapy, which appeared as promising treatment strategies for various disease conditions. Cell therapies employ stem cells, or cells grown from stem cells, to replace or rejuvenate damaged tissue. Numerous findings have suggested a significant therapeutic advantage with the utilization of cell therapeutic approaches in various neurological disorders including amyotrophic lateral sclerosis, various heart disorders involving endstage ischaemic heart diseases, myocardial infarction, or preventing vascular restenosis. Various bone fractures are also reported to benefit from cell therapy including osteogenesis imperfecta. Nonetheless, cell therapy has its drawbacks, which include the risk of tumorigenesis or immune rejection. The therapy also faces ethical and political controversies besides scientific challenges. Consequently, efforts are made towards the development of stem cell secretome which are the secreted factors produced by the stem cells that are responsible for mediating and modulating stem cells effects in the disease condition. The secretome holds various added advantages: it can be manufactured, freeze-dried, packaged, and transported more easily which is some of the numerous advantages of using secretome over the use of stem cells. Besides, as secretome is free from cells, there is no need to match the donors and recipients to avoid the risk of rejection. For that reason, stem cell-derived secretome is a promising possibility to be used as pharmaceuticals for regenerative medicine. Up till now, there have have been limited clinical trials utilizing secretome in certain disease conditions.