: Follistatin-like 1 (FSTL1), a secreted glycoprotein, has been shown to participate in regulating developmental processes and to be involved in states of disease and injury. Spatiotemporal regulation and posttranslational modifications contribute to its specific functions and make it an intriguing candidate to study disease mechanisms and potentially develop new therapies. With cardiovascular diseases as the primary cause of death worldwide, clarification of mechanisms underlying cardiac regeneration and revascularization remains essential. Recent findings on FSTL1 in both acute coronary syndrome and heart failure emphasize its potential as a target for cardiac regenerative therapy. With this review, we aim to shed light on the role of FSTL1 specifically in cardiovascular disease and inflammation.

Cardiac cell therapy is a strategy to treat patients with chronic myocardial infarction (MI). No consensus exists regarding the optimal cell type. First, a comparison between autologous bone marrow-derived mononuclear cells (BMMNC) and mesenchymal stem cells (MSC) on therapeutic efficacy after MI was performed. Next, the effect of repetitive, NOGA-guided transendocardial injection was determined via a crossover design. Nineteen pigs were allocated in three groups: (1) placebo (at 4 and 8 weeks), (2) MSC (followed by placebo at 8 weeks), or (3) BMMNC (followed by MSC at 8 weeks) delivery including a priming strategy to enhance MSC effect. At 4 weeks, ejection fraction (EF) was significantly improved after MSC injection and not by BMMNC injection. After 8 weeks, no difference was observed in EF between cell-treated groups demonstrating the positive systolic effect of MSC. This study showed that MSC rather than BMMNC injection improves systolic function in chronic MI.

An important aspect of cell therapy in the field of cardiac disease is safe and effective delivery of cells. Commonly used delivery strategies such as intramyocardial injection and intracoronary infusion both present with advantages and disadvantages. Therefore, alternative delivery routes are explored, such as retrograde coronary venous infusion (RCVI). Our aim is to evaluate safety and efficiency of RCVI by providing a complete overview of preclinical and clinical studies applying RCVI in a broad range of disease types and experimental models. Available data on technical and safety aspects of RCVI are incomplete and insufficient. Improvement of cardiac function is seen after cell delivery via RCVI. However, cell retention in the heart after RCVI appears inferior compared to intracoronary infusion and intramyocardial injection. Adequately powered confirmatory studies on retention rates and safety are needed to proceed with RCVI in the future.Electronic supplementary materialThe online version of this article (10.1007/s12265-018-9785-1) contains supplementary material, which is available to authorized users.

BackgroundCommonly used strategies for cell delivery to the heart are intramyocardial injection and intracoronary (IC) infusion, both having their advantages and disadvantages. Therefore, alternative strategies, such as retrograde coronary venous infusion (RCVI), are explored. The aim of this confirmatory study was to compare cardiac cell retention between RCVI and IC infusion. As a secondary end point, the procedural safety of RCVI is assessed.MethodsFour weeks after myocardial infarction, 12 pigs were randomised to receive mesenchymal stromal cells, labelled with Indium-111, via RCVI (n=6) or IC infusion (n=6). Four hours after cell administration, nuclear imaging was performed to determine the number of cells retained in the heart both in vivo and ex vivo. Procedure-related safety measures were reported.ResultsCardiac cell retention is significantly lower after RCVI compared with IC infusion (in vivo: RCVI: median 2.89% vs IC: median 13.74%, p=0.002, ex vivo: RCVI: median 2.55% vs IC: median 39.40%, p=0.002). RCVI led to development of pericardial fluid and haematomas on the frontal wall of the heart in three cases. Coronary venous dissection after RCVI was seen in three pigs, of which one also developed pericardial fluid and a haematoma. IC infusion led to no flow in one pig.ConclusionRCVI is significantly less efficient in delivering cells to the heart compared with IC infusion. RCVI led to more procedure-related safety issues than IC infusion, with multiple cases of venous dissection and development of haematomas and pericardial fluid collections.