Short-Term Heart Retention and Distribution of Intramyocardial Delivered Mesenchymal Cells within Necrotic or Intact Myocardium

Abstract

Cell therapy with bone marrow mesenchymal stem cells (BMSCs) is a new strategy for treating ischemic heart failure, but data concerning the distribution and retention of transplanted cells remain poor. We investigated the short-term myocardial retention of BMSCs when these cells are directly injected within necrotic or intact myocardium. 111 Indium-oxine-labeled autologous BMSCs were injected within either 1-month-old infarction (n = 6) or normal myocardium (n = 6) from rats. Serial in vivo pinhole scintigraphy was scheduled during 1 week in order to track the implanted cells. The myocardial retention of BMSCs was definitely higher in myocardial infarction than in normal myocardial area (estimated percent retention at 2 h: 63 ± 3% vs. 25 ± 4%, p < 0.001) and the estimated cardiac retention values were unchanged in both groups along the 7 days of follow-up. On heart sections at day 7, labeled BMSCs were still around the injection site and appeared confined to the scarred tissue corresponding either to the infarct area or to the myocardium damaged by needle insertion. BMSCs have a higher retention when they are injected in necrotic than in normal myocardial areas and these cells appear to stay around the injection site for at least a 7-day period.

SDF-1 Recruits Cardiac Stem Cell-Like Cells that Depolarize In Vivo

“…We and others have been unable to demonstrate cardiac myocyte regeneration from mesenchymal stem cells (24), recruited CD117 + , or hematopoietic stem cells (2,3,7,13,20). In our recent study (24) and this study we have been unable to demonstrate that endogenous stem cells are responsible for the increase in cardiac myocyte number following the prolongation of SDF-1 expression after AMI.…”

Permanently Hypoxic Cell Culture Yields Rat Bone Marrow Mesenchymal Cells with Higher Therapeutic Potential in the Treatment of Chronic Myocardial Infarction

“…We have developed an isotopic labelling that allowed cell follow-up in vivo but it was efficient only for a very short period, i.e. 7 days [27]. Long-term cell tracking is still a challenging technique that requires both development and careful examination.…”

“…As previously described [17, 27], the bone marrow was harvested (n=27) through tibial puncture using a 28-gauge needle. The obtained bone marrow solution was centrifuged at 400g for 10 minutes.…”

“…At the same time as harvesting the bone marrow, myocardial infarction (MI) was induced in 27 animals by means of permanent coronary ligation, as previously described [27]. In brief, the hearts were accessed via left anterolateral thoracotomy through the fifth intercostal space.…”

In Vivo SPECT Quantification of Transplanted Cell Survival After Engraftment Using 111In-Tropolone in Infarcted Canine Myocardium

“…This may not accurately reflect leakage from transplanted BMSCs, because leakage potentially differs between different cell populations. However, we decided that in vitroacquired leakage estimates to correct in vivo data as previously done (27) could not adequately account for in vivo biologic complexity.…”