Clinical Studies of Cell Therapy in Cardiovascular Medicine

Abstract

Given the rising prevalence of cardiovascular disease worldwide and the limited therapeutic options for severe heart failure, novel technologies that harness the regenerative capacity of the heart are sorely needed. The therapeutic use of stem cells has the potential to reverse myocardial injury and improve cardiac function, in contrast to most current medical therapies that only mitigate heart failure symptoms. Nearly 2 decades and >200 trials for cardiovascular disease have revealed that most cell types are safe; however, their efficacy remains controversial, limiting the transition of this therapy from investigation to practice. Lessons learned from these initial studies are driving the design of new clinical trials; higher fidelity of cell isolation techniques, standardization of conditions, more consistent use of state of the art measurement techniques, and assessment of multiple end points to garner insights into the efficacy of stem cells. Translation to clinical trials has almost outpaced our mechanistic understanding, and individual patient factors likely play a large role in stem cell efficacy. Therefore, careful analysis of dosing, delivery methods, and the ideal patient populations is necessary to translate cell therapy from research to practice. We are at a pivotal stage in the field in which information from many relatively small clinical trials must guide carefully executed efficacy trials. Larger efficacy trials are being launched to answer questions about older, first-generation stem cell therapeutics, while novel, second-generation products are being introduced into the clinical realm. This review critically examines the current state of clinical research on cell-based therapies for cardiovascular disease, highlighting the controversies in the field, improvements in clinical trial design, and the application of exciting new cell products.

Time to end the war on cell therapy

“…Of note, MSC‐HF utilized autologous BM‐MSCs. Most cardiovascular trials nowadays use allogeneic MSCs, which may be more effective because they avoid the potential confounding effects of comorbidities . Given that transplanted cells do not differentiate into cardiomyocytes and do not survive more than a few weeks, it is remarkable that the salubrious effects of a single injection of BM‐MSCs persisted for at least 12 months.…”

“…As can be expected in the initial development of a novel treatment, many studies have been performed that are small, underpowered, or poorly designed. The vast majority of data in patients with ST‐elevation myocardial infarction does not support efficacy . Nevertheless, there is Phase II evidence that cell therapy is beneficial in ischaemic HF and refractory angina .…”

Immune Dysregulation in HFpEF: A Target for Mesenchymal Stem/Stromal Cell Therapy

“…Thus, MSCs may target both systemic inflammation and the cardiac pathological changes associated with HFpEF. However, MSC therapy in cardiovascular disease remains of unclear utility, owing to the limited results from relatively small clinical trials, as well as an incomplete understanding of their mechanism of action [46,47].…”

Cardiac Progenitor Cells from Stem Cells: Learning from Genetics and Biomaterials

“…The end-goal of in vitro and animal in vivo studies in CPC research is to provide enough evidence regarding the efficacy and safety of cell therapies for further application in human trials. This is not without the caveat that, despite promising results from in vitro and animal models, the translation to clinical trials still suffer from serious inefficiencies in desirable outcomes over long term, costing billions of dollars in the process [280]. Even though there is not yet an agreement on the CPC population that displays the best regenerative capacity, a variety of CPCs have been used or are being used in clinical trials, which are summarized in Table 6.…”