Mesenchymal Stem Cell Therapy for the Treatment of Heart Failure Caused by Ischemic or Non-ischemic Cardiomyopathy: Immunosuppression and Its Implications

Abstract

HF patients with signs and symptoms of worsening heart failure (HF), despite optimal medical therapy, have a poor prognosis. The pathways contributing to HF are multiple, probably accounting, in part, for current treatment approaches not being more effective. Stem cells, particularly mesenchymal stem cells (MSCs), have a broad range of activities, making them particularly interesting candidates for a new HF therapeutic. This review presents an overview of the studies examining the efficacy of stem cell studies administered to HF patients, focusing mainly on MSCs. It examines the issues surrounding autologous vs. allogenic stem cells, the results of different routes of administration, and implications deriving from the belief that for stem cells to be effective, they must engraft in the myocardium and exert local effects. Since intravenous administration of stem cells leads to sparse cardiac engraftment, stem cell delivery strategies have uniformly involved catheter-based delivery systems. This becomes problematic in a disease that will almost certainly require delivery of the therapeutic throughout the course of the disease. Importantly, it appears that a critical contributing cause of the progressive cardiac dysfunction experienced by HF patients is the existence of a persistent inflammatory response. Since MSCs exert potent anti-inflammatory effects through paracrine mechanisms, it is possible that intravenous delivery of MSCs may be therapeutically effective. If this concept is valid, it could lead to a transformational change in stem cell delivery strategies.

Comparison of Mesenchymal Stem Cell Efficacy in Ischemic Versus Nonischemic Dilated Cardiomyopathy

“…Two recent large meta‐analyses highlighted the paucity of high quality clinical trials assessing the evidence of MSC therapy in ICM and DCM 22, 23. Similarly, to date, there has not been a comparison between MSC therapy in patients with ICM and DCM.…”

Persistent Inflammation, Stem Cell–Induced Systemic Anti‐Inflammatory Effects, and Need for Repeated Stem Cell Injections: Critical Concepts Influencing Optimal Stem Cell Strategies for Treating Acute Myocardial Infarction and Heart Failure

“…1 This conclusion has not changed with time. 2,3 Similar conclusions are applicable to clinical trials of AMI. Although smaller trials found stem cells improve myocardial outcomes, pivotal trials have not definitively improved their prospectively identified primary end points.…”

“…They concluded “ … to date, no cell therapy has been conclusively shown to be effective in patients with HF.” 1 This conclusion has not changed with time 2, 3. Similar conclusions are applicable to clinical trials of AMI.…”

Application and prospect of adipose stem cell transplantation in treating lymphedema

“…Lymphedema, characterized by tissue swelling, lipid deposition, and fibrosis due to excess accumulation of interstitial fluid and inadequate lymphatic drainage, affects 0.13%-2% of the global population[ 5 ] and remains a chronic, debilitating and incurable disease. Stem cell-based regenerative medicine has shown great promise for refractory diseases, such as inflammatory bowel diseases[ 33 ], heart failure[ 34 ], osteoarthritis[ 35 ], rheumatoid arthritis[ 36 ], and graft-versus-host disease[ 37 ]. With the properties of self-renewal, multipotential differentiation, paracrine, immunomodulatory, and trophic effects, and low immunogenicity alongside their practical advantages, ADSCs have become one of the most promising candidates for regenerative medicine.…”