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.
Highlights
Transplantation of stem and progenitor cells is emerging as a promising therapeutic option for repair of ischemic and infarcted myocardium [1,2,3]
The 99mTc radioactivity detected in bone marrow cells (BMC) and in the supernatant revealed that only 33.062.5% of the radioactivity initially incorporated remained within the cells 24 hours after labeling
Cardiac cell accumulation according to timing of therapy To determine the best moment to administer cells post-myocardial infarction (MI), the radiolabeled BMCs were delivered through 4 different routes at 1, 2, 3 or 7 days post-infarction
Summary
Transplantation of stem and progenitor cells is emerging as a promising therapeutic option for repair of ischemic and infarcted myocardium [1,2,3]. Studies investigating the kinetics of cytokines production and mobilization of stem cells to the injured myocardium provide evidence that these processes occur within a limited time window after infarction [4,5,6]. This provides a rational for identification of the ideal timing for cell transplantation. Cell therapy approaches for biologic cardiac repair hold great promises, 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
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