Delivery Route in Bone Marrow Cell Transplantation Should be Optimized According to the Etiology of Heart Disease

Abstract

Preparation of BMCsBMCs were harvested from 8-week-old syngenic and transgenic male C57Bl/6 mice expressing enhanced green fluorescent protein (GFP), by flushing the femurs and tibias Circ J 2008; 72: 1528 -1535 (Received August 23, 2006 revised manuscript received April 28, 2008; accepted May 9, 2008 Background Recent studies have revealed that bone marrow cell (BMC) transplantation is effective not only for myocardial infarction (MI), but also for dilated cardiomyopathy (DCM). However, the method of administering donor cells remains unknown, and may differ between MI and DCM. In the present study, intramyocardial (IM) injection and intravenous (IV) delivery of BMC were compared in each etiological model. Methods and Results MI was induced in 72 mice and DCM in another 36 mice by doxorubicin. BMCs were administered IV or IM in an acute MI (AMI), old MI (OMI) or DCM model. In the AMI model, left ventricular (LV) remodeling was reduced in both the IM-and IV-groups, but only in the IM-group in the OMI model. In the DCM model, the LV dimension of the IV-group was smaller than that of the IM-group. Histological examination showed that green fluorescent protein (GFP) cells were equally distributed in the infarct area of the IV-and IMgroups in AMI, and in the IM-group in the OMI model. In the DCM model, GFP cells were diffusely scattered throughout the ventricular wall in the IV-group, but were confined to the injection site in the IM-group. Conclusions In OMI, IM delivery of BMCs was more effective than IV; however, IV delivery was superior in DCM. Delivery route should be selected according to the etiology of heart disease to optimize the efficacy of BMC transplantation. (Circ J 2008; 72: 1528 -1535

Stromal Vascular Fraction Transplantation as an Alternative Therapy for Ischemic Heart Failure: Anti-inflammatory Role

“…To isolate mononuclear cells, the gradient centrifugation method with Percoll was used [16]. After the cells were washed in PBS for 3 times, labeled with a fluorescent dye using PKH26, before suspended in 0.1 mL of culture medium (without serum) at a concentration of 6 × 10 7 /mL cells for transplantation.…”

Stem Cell Therapy for Chronic Myocardial Infarction

“…Regarding functional evaluation, small animal models are most frequently evaluated by 2D echocardiography [2,20,33,45,53,88,89], being also employed for pigs [24,81] or dogs [77]. However, MRI is considered [73,81] as the "gold standard" for assessing ventricular function and geometry.…”

“…This group also found that the benefit was related to a greater prevention of ventricular dilatation and preservation of ECM architecture through influence in the MMP/TIMP system. In a mouse model, Nakajima et al [53] transplanted 20 millions of BM-MNC in acute (6 h post-MI) or chronic (at 4 weeks) MI, finding that treatment induced a significant recovery of cardiac function only when cells were intramyocardially injected in the chronic phase, with no effect in the acute stage. It is possible that once again, the inflammatory microenvironment played a role in cell disappearance, but other factors as the high dose employed (over 200 times the usual dose for mice) could have contributed to injected cell necrosis.…”

“…Either route showed similar functional effects on ventricular contractility, vascular density, and fibrosis 3 months after transplantation, but the percutaneous approach presents the advantage of being clearly less invasive. On the other hand, when intravenous and intramyocardial BM cell injections were compared in a mouse model of chronic MI, it was found that only direct cardiac transplantation induced a significant recovery of cardiac contractility [53], probably related to the differences in the level of engraftment.…”

Rejuvenation: an integrated approach to regenerative medicine

“…The transportation system not only ensures the remote communication between the injured site and the repair mechanism [ 48 ], but also serves as the essential conduit for the delivery of the repairing materials to the injured site. In the study of myocardial ischemic injury, it was found that intravenous injection of bone marrow stem cells improved the recovery of acute ischemic infarction, but the same treatment had no effect on the chronic ischemic infarction [ 51 – 54 ]. In the latter case, the homing of labeled stem cells was not identified in the infarcted area, otherwise, it took place in the acute infarction [ 51 ].…”