Effect of Aging on Human Mesenchymal Stem Cell Therapy in Ischemic Cardiomyopathy Patients

Abstract

BACKGROUND The role of patient age on the efficacy of mesenchymal stem cell (MSC) therapy in ischemic cardiomyopathy (ICM) is controversial. OBJECTIVE We sought to determine whether the therapeutic effect of culture-expanded MSCs persists even in older subjects. METHODS Patients with ICM who received MSCs via transendocardial stem cell injection (TESI) as part of the TAC-HFT (n = 19) and POSEIDON (N = 30) clinical trials were divided into 2 age groups: <60 versus ≥60 years. Functional capacity was measured by 6-minute walk distance (6MWD) and quality of life using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, measured at baseline, 6 months, and 1-year post-TESI. Various cardiac imaging parameters, including absolute scar size, were compared at baseline and 1 year post-TESI. RESULTS Mean 6MWD was similar at baseline and increased at 1 year post-TESI in both groups: 48.5 ± 14.6 m (p = 0.001) for the younger and 35.9 ± 18.3 m (p = 0.038) for the older participants (p = NS between groups). The older group exhibited a significant reduction in MLHFQ score (−7.04 ± 3.54; p = 0.022), while the <60 age group had a borderline significant reduction (−11.22 ± 5.24; p = 0.058) from baseline (p = NS between groups). While there were significant reductions in absolute scar size from baseline to 1 year post-TESI, the effect did not differ by age. CONCLUSION MSC therapy via TESI in ICM patients improves 6MWD and MLHFQ score and reduces MI size. Importantly, age did not impair response.

Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease

“…Understanding the effect of aging on MSCs is crucial for autologous therapy for older patients, who are typically afflicted by cardiovascular diseases. In a recently published sub-study 156 from the TAC-HFT and POSEIDON trials, it was reported that older individuals did not have an impaired response to MSC therapy.…”

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction

“…All other authors, who are not complex processes in vivo like multilineage growth and differentiation, angiogenesis, and ventricular remodeling, while pharmacologic therapy predictably targets a single cellular receptor for efficacy. Further confounding CCT is the choice of therapeutic cells (4,9) and cell delivery techniques (10), as well as the impact of host factors (11), suggesting that new approaches are needed to link data between model systems (12).…”

Cardiac aging — Getting to the stem of the problem

“…Findings from TAC-HFT and POSEIDON clinical trials using MSCs in patients with ischemic cardiomyopathy demonstrate that the chronological age of the recipient does not affect the efficacy of the treatment [37]. Functional improvements and scar size reduction following cell therapy were comparable between patients older and younger than 60 years of age.…”

“…Functional improvements and scar size reduction following cell therapy were comparable between patients older and younger than 60 years of age. Although the cellular and functional characteristics of the donor MSCs as well as the recipient’s endogenous CPCs were not studied, this finding demonstrates that stem cell therapy using exogenously expanded MSCs can circumvent chronological age of the recipient and potentiate cardiac repair [37]. Treatment with MSCs also enhances proliferation and differentiation of endogenous CPCs, suggesting that stem cell interactions may be an important mechanism for success in stem-cell based therapy [38].…”