Cell Therapy Attenuates Cardiac Dysfunction Post Myocardial Infarction: Effect of Timing, Routes of Injection and a Fibrin Scaffold

Abstract

BackgroundCell therapy approaches for biologic cardiac repair hold great promises, although basic fundamental issues remain poorly understood. In the present study we examined the effects of timing and routes of administration of bone marrow cells (BMC) post-myocardial infarction (MI) and the efficacy of an injectable biopolymer scaffold to improve cardiac cell retention and function.Methodology/Principal Findings 99mTc-labeled BMC (6×106 cells) were injected by 4 different routes in adult rats: intravenous (IV), left ventricular cavity (LV), left ventricular cavity with temporal aorta occlusion (LV+) to mimic coronary injection, and intramyocardial (IM). The injections were performed 1, 2, 3, or 7 days post-MI and cell retention was estimated by γ-emission counting of the organs excised 24 hs after cell injection. IM injection improved cell retention and attenuated cardiac dysfunction, whereas IV, LV or LV* routes were somewhat inefficient (<1%). Cardiac BMC retention was not influenced by timing except for the IM injection that showed greater cell retention at 7 (16%) vs. 1, 2 or 3 (average of 7%) days post-MI. Cardiac cell retention was further improved by an injectable fibrin scaffold at day 3 post-MI (17 vs. 7%), even though morphometric and function parameters evaluated 4 weeks later displayed similar improvements.Conclusions/SignificanceThese results show that cells injected post-MI display comparable tissue distribution profile regardless of the route of injection and that there is no time effect for cardiac cell accumulation for injections performed 1 to 3 days post-MI. As expected the IM injection is the most efficient for cardiac cell retention, it can be further improved by co-injection with a fibrin scaffold and it significantly attenuates cardiac dysfunction evaluated 4 weeks post myocardial infarction. These pharmacokinetic data obtained under similar experimental conditions are essential for further development of these novel approaches.

Scaffold-based delivery of adipose tissue-derived stem cells in rat frozen-thawed ovarian autografts: preliminary studies in a rat model

“…Rat adiposederived stem cells (rASCs) were isolated, characterized, and maintained in culture as previously described [22,23].…”

A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart

“…17,20 Previous studies have also demonstrated that fibrin glue could improve the survival of injectable skeletal myoblasts, bone marrow cells, marrowderived cardiac stem cells, adipose-derived stem cells, and human induced pluripotent stem cell-derived cardiomyocytesin MI hearts. [21][22][23][24][25][26] Furthermore, injection of fibrin alone (without cells) could preserve cardiac function after MI and prevent negative LV remodeling. 27 Also, our previous report has demonstrated the positive role of platelet fibrin gel in cardiac repair after MI.…”

Percutaneous Fluoroscopic-Guided Endomyocardial Delivery in an Experimental Model of Left Ventricular Assist Device Support

“…Besides the optimal timing for cell therapy, the route of administration is also of importance to receive the best efficacy of transplanted cells [13]. In the setting of heart failure, cardiopoietic and mesenchymal stem cells were delivered by endomyocardial injections guided by left ventricular electromechanical mapping [11,14].…”