Local Cell Delivery Research Articles

Issue Highlights

HomeCirculationVol. 113, No. 21Issue Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIssue Highlights Originally published30 May 2006https://doi.org/10.1161/circ.113.21.2473Circulation. 2006;113:2473IMPACT OF TRANSFORMING GROWTH FACTOR-β1 ON ATRIOVENTRICULAR NODE CONDUCTION MODIFICATION BY INJECTED AUTOLOGOUS FIBROBLASTS IN THE CANINE HEART, by Bunch et al.Pharmacological treatment of atrial fibrillation using antiarrhythmic agents or ventricular rate control is challenging because of variable success and medication side effects. Catheter ablation also is not 100% successful and carries the risk of procedural complications. In this issue of Circulation, Bunch and colleagues describe a technique of percutaneously injecting cultured fibroblasts from skin biopsies to modulate atrioventricular (AV) nodal conduction and rate control in a canine model. Using electroanatomic mapping and intracardiac echocardiography to guide delivery, they injected fibroblasts (with or without transforming growth factor-β1) through a NOGA catheter at several AV nodal input regions. Regulation of AV nodal conduction and ventricular rate reduction during induced atrial fibrillation was observed and was more pronounced in dogs receiving transforming growth factor-β1–treated fibroblast injections. There were no major complications or long-term high-grade AV block. Local cell delivery may eventually be a potential therapeutic option, perhaps combined with medication and/or device therapy to modulate ventricular rate control during atrial arrhythmias. See p 2485 (and editorial on p 2474).ENHANCED VENTRICULAR UNTWISTING DURING EXERCISE: A MECHANISTIC MANIFESTATION OF ELASTIC RECOIL DESCRIBED BY DOPPLER TISSUE IMAGING, by Notomi et al.Classical concepts of myocardial function learned by all cardiologists center around pressure-volume relationships in the right and left ventricles. It is important to realize, however, that the sequence and pattern of contraction of the 2 ventricles is different: The right ventricle contracts more like a bellows, but the left ventricle undergoes a complex cycle of twisting and untwisting in systole and diastole. Notomi et al provide a detailed analysis of left ventricular (LV) untwisting both at rest and during exercise using Doppler tissue imaging. Although healthy volunteers enhance the rate of untwisting during exercise, thus increasing the diastolic intraventricular pressure gradient (facilitating LV “suction”), patients with hypertrophic cardiomyopathy have a blunted untwisting response to exercise. The new insights into the dynamic relationship between LV systolic and diastolic function described in this paper offer new tools for evaluating diastolic LV function in a variety of cardiovascular disease states and potentially monitoring the response to therapy. See p 2524.PERCUTANEOUS TREATMENT WITH DRUG-ELUTING STENT IMPLANTATION VERSUS BYPASS SURGERY FOR UNPROTECTED LEFT MAIN STENOSIS: A SINGLE-CENTER EXPERIENCE, by Chieffo et al.Coronary artery bypass grafting (CABG) is the preferred revascularization strategy for left main coronary artery (LMCA) disease. Improvements in results with percutaneous coronary intervention (PCI) with drug-eluting stents (DES) have led interventional cardiologists to perform unprotected LMCA procedures. Clinical trial evidence supporting such an approach is lacking, however. In this issue of Circulation, Chieffo et al report the single-center retrospective experience in patients with LMCA stenosis treated with PCI and DES (n=107) or CABG (n=142). At 1 year, there was no difference in the degree of protection against death, stroke, myocardial infarction, and revascularization between PCI with DES and CABG for LMCA disease. These results support the need for randomized trials with longer clinical follow-up to define optimal revascularization strategies for LMCA disease. See p 2542.Visit http://circ.ahajournals.org:Images in Cardiovascular MedicineUntreated 37-Year-Old Homozygous Familial Hypercholesterolemic Smoker. See p e777.Near Sudden Death From Cardiac Lipoma in an Adolescent. See p e778.Left Ventricular Pseudoaneurysm: A Late Complication of Low-Energy DC Ablation. See p e780. Download figureDownload PowerPointCorrespondenceSee p e782. Previous Back to top Next FiguresReferencesRelatedDetails May 30, 2006Vol 113, Issue 21 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.113.21.2473 Originally publishedMay 30, 2006 PDF download Advertisement

Cell therapy for bone disease: a review of current status.

Bone marrow is a reservoir of pluripotent stem/progenitor cells for mesenchymal tissues. Upon in vitro expansion, in vivo bone-forming efficiency of bone marrow stromal cells (BMSCs) is dramatically lower in comparison with fresh bone marrow, and their in vitro multidifferentiation potentials are gradually lost. Nevertheless, when BMSCs are isolated and expanded in the presence of fibroblast growth factor 2, the percentage of cells able to differentiate into the osteogenic, chondrogenic, and adipogenic lineages is greater. Osteogenic progenitors are not exclusive to skeletal tissues. We could also think of cells in different adult tissues as potentially capable of following an osteochondrogenic differentiation pathway, but, under normal physiological conditions, they are inhibited in this process by the environment and/or the adjacent cell populations. When, for some reason such as pathology, the environment changes dramatically and the inhibiting condition is removed, these cells could become osteoblasts. Bone is repaired via local delivery of cells within a scaffold. Bone formation was first assessed in small animal models. Large animal models were successively developed to prove the feasibility of the tissue engineering approach in a model closer to a real clinical situation. Eventually, pilot clinical studies were performed. Extremely appealing is the possibility of using mesenchymal progenitors in the therapy of genetic bone diseases via systemic infusion. There is experimental evidence to suggest that mesenchymal progenitors delivered by this route engraft with a very low efficiency and do not produce relevant and durable clinical effects. Under some conditions, where the local microenvironment is either altered (i.e., injury) or under important remodeling processes (i.e., fetal growth), engraftment of stem and progenitor cells seems to be enhanced. A better understanding of their engraftment mechanisms will, hopefully, extend the field of therapeutic applications of mesenchymal progenitors.

Intracoronary Infusion of Skeletal Myoblasts Improves Cardiac Function in Doxorubicin-Induced Heart Failure

Background Skeletal myoblast transplantation is promising for the treatment of end-stage heart failure. Direct intramyocardial injection is useful for local cell delivery but may not be effective in global dissemination of cells into the heart, which would be advantageous in treating generalized cardiac dysfunction as in dilated cardiomyopathy. We hypothesized that intracoronary infusion of myoblasts would disseminate cells more effectively, leading to functional improvement in global heart failure. Methods and Results Heart failure was induced by the intraperitoneal administration of doxorubicin (total dose 15 mg/kg) in rat. One million primary skeletal myoblasts were then infused via the coronary arteries of an excised, failing doxorubicin-treated heart. After incubation under increased intracoronary pressure, the hearts were subsequently transplanted into syngeneic recipients. For the control group, doxorubicin-treated hearts were infused with medium only and transplanted. Four weeks after transplantation, Langendorff perfusion demonstrated that both maximum dP/dt (2797.6±103.3 versus 2326.9±133.1 mm Hg/s, P =0.01) and minimum dP/dt (−2067.4±88.1 versus −1718.8±91.3 mm Hg/s, P =0.02) were improved in myoblast-transplanted hearts compared with medium-infused hearts. This was associated with a sharper slope of the left ventricular developed pressure-volume curve and a reduced slope of the end-diastolic pressure-volume relation in the myoblast-transplanted hearts. Immunohistochemistry for skeletal myosin heavy chain showed that globally disseminated myoblasts had survived and differentiated into multinucleated myotubes that had aligned with the cardiac fiber axis within host myocardium. No significant myocardial infarction was observed. Conclusions We demonstrated the feasibility and efficiency of skeletal myoblast transplantation via the intracoronary route as a promising strategy for improving cardiac function in global heart failure.

Intracoronary infusion of skeletal myoblasts improves cardiac function in doxorubicin-induced heart failure.

Skeletal myoblast transplantation is promising for the treatment of end-stage heart failure. Direct intramyocardial injection is useful for local cell delivery but may not be effective in global dissemination of cells into the heart, which would be advantageous in treating generalized cardiac dysfunction as in dilated cardiomyopathy. We hypothesized that intracoronary infusion of myoblasts would disseminate cells more effectively, leading to functional improvement in global heart failure. Heart failure was induced by the intraperitoneal administration of doxorubicin (total dose 15 mg/kg) in rat. One million primary skeletal myoblasts were then infused via the coronary arteries of an excised, failing doxorubicin-treated heart. After incubation under increased intracoronary pressure, the hearts were subsequently transplanted into syngeneic recipients. For the control group, doxorubicin-treated hearts were infused with medium only and transplanted. Four weeks after transplantation, Langendorff perfusion demonstrated that both maximum dP/dt (2797.6+/-103.3 versus 2326.9+/-133.1 mm Hg/s, P=0.01) and minimum dP/dt (-2067.4+/-88.1 versus -1718.8+/-91.3 mm Hg/s, P=0.02) were improved in myoblast-transplanted hearts compared with medium-infused hearts. This was associated with a sharper slope of the left ventricular developed pressure-volume curve and a reduced slope of the end-diastolic pressure-volume relation in the myoblast-transplanted hearts. Immunohistochemistry for skeletal myosin heavy chain showed that globally disseminated myoblasts had survived and differentiated into multinucleated myotubes that had aligned with the cardiac fiber axis within host myocardium. No significant myocardial infarction was observed. We demonstrated the feasibility and efficiency of skeletal myoblast transplantation via the intracoronary route as a promising strategy for improving cardiac function in global heart failure.