Allogeneic cardiac stem cell administration for acute myocardial infarction

Abstract

Myocardial infarction, even after reperfusion, leads to significant loss of cardiomyocytes and to a maladaptive remodeling process. A possibility gaining attention as an ancillary therapy is the use of cardiac-derived cell products, with early stage clinical trials reporting highly promising results with autologous cells. However, an autologous therapy presents limitations, such as timeframe of therapy, cell processing and culture costs, risks posed to the patient by the tissue harvesting, etc. Allogeneic cells may represent an answer, providing an off-the-shelf product that could be used in the acute stage, before the myocardial damage is irrevocable. To date, allogeneic cardiac-derived cell products are being tested extensively, but the questions of their immunogenicity (and therefore safety), efficacy, cost–effectiveness, etc. are only partially elucidated. Small Phase I/II clinical trials (ALLSTAR, CAREMI) have started and their results will shed the much needed light on the feasibility and safety of a much needed therapy.

Keywords:

• allogeneic
• animal models
• cardiac stem cells
• experimental therapy
• myocardial infarction
• myocardial regeneration

Financial & competing interests disclosure

This paper has been funded via the European FP7-HEALTH-2009-1.4-3, Grant Agreement 242038. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Cell-based therapies aiming at myocardial regeneration have the potential to transform the clinical management and prognosis of myocardial infarction and heart failure.

• Highly promising results have recently been reported from the first clinical trials to use autologous cardiac cells in the setting of heart failure, either after coronary artery bypass grafting [19,20] (SCIPIO trial, [21]) or after coronary stenting [22,23] (CADUCEUS trial, [24]).

• Allogeneic cells emerge as a promising option and several studies using this strategy have been reported [13,27–30]. The advantages of using an allogeneic product are varied. They offer the possibility of administering the cells very early after the ischemic event, as an ‘off-the-shelf’ product that, at the same time, can be subjected to higher quality controls than autologous products.

• There are several heart-derived cell populations described to date, expressing different characteristics and/or surface markers: c-kit+, Sca-1+, side population cells, Isl1+, cardiospheres and cardiosphere-derived cells.

• Heart-derived products are suspected to act via a paracrine activation of endogenous cardiac stem cell immunomodulation.

• Rodent studies with different heart-derived cell types have confirmed their safety and potential (data).

• Swine studies support these results and help in defining dose, administration route and similar questions.

• Early clinical trials have been started. Preliminary safety results are available in the ALLSTAR trial, and Phase II has been started in view of the said results.

Notes