Igor Jakoniuk

Bio: Igor Jakoniuk is an academic researcher from New York Medical College. The author has contributed to research in topics: Heart failure & Bone marrow. The author has an hindex of 4, co-authored 4 publications receiving 8565 citations.

Bone marrow cells regenerate infarcted myocardium

Abstract: Myocardial infarction leads to loss of tissue and impairment of cardiac performance The remaining myocytes are unable to reconstitute the necrotic tissue, and the post-infarcted heart deteriorates with time1 Injury to a target organ is sensed by distant stem cells, which migrate to the site of damage and undergo alternate stem cell differentiation2,3,4,5; these events promote structural and functional repair6,7,8 This high degree of stem cell plasticity prompted us to test whether dead myocardium could be restored by transplanting bone marrow cells in infarcted mice We sorted lineage-negative (Lin-) bone marrow cells from transgenic mice expressing enhanced green fluorescent protein9 by fluorescence-activated cell sorting on the basis of c-kit expression10 Shortly after coronary ligation, Lin- c-kitPOS cells were injected in the contracting wall bordering the infarct Here we report that newly formed myocardium occupied 68% of the infarcted portion of the ventricle 9 days after transplanting the bone marrow cells The developing tissue comprised proliferating myocytes and vascular structures Our studies indicate that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease

Mobilized bone marrow cells repair the infarcted heart, improving function and survival

Abstract: Attempts to repair myocardial infarcts by transplanting cardiomyocytes or skeletal myoblasts have failed to reconstitute healthy myocardium and coronary vessels integrated structurally and functionally with the remaining viable portion of the ventricular wall. The recently discovered growth and transdifferentiation potential of primitive bone marrow cells (BMC) prompted us, in an earlier study, to inject in the border zone of acute infarcts Lin− c-kitPOS BMC from syngeneic animals. These BMC differentiated into myocytes and vascular structures, ameliorating the function of the infarcted heart. Two critical determinants seem to be required for the transdifferentiation of primitive BMC: tissue damage and a high level of pluripotent cells. On this basis, we hypothesized here that BMC, mobilized by stem cell factor and granulocyte-colony stimulating factor, would home to the infarcted region, replicate, differentiate, and ultimately promote myocardial repair. We report that, in the presence of an acute myocardial infarct, cytokine-mediated translocation of BMC resulted in a significant degree of tissue regeneration 27 days later. Cytokine-induced cardiac repair decreased mortality by 68%, infarct size by 40%, cavitary dilation by 26%, and diastolic stress by 70%. Ejection fraction progressively increased and hemodynamics significantly improved as a consequence of the formation of 15 × 106 new myocytes with arterioles and capillaries connected with the circulation of the unaffected ventricle. In conclusion, mobilization of primitive BMC by cytokines might offer a noninvasive therapeutic strategy for the regeneration of the myocardium lost as a result of ischemic heart disease and, perhaps, other forms of cardiac pathology.

Myocardial Cell Death in Human Diabetes

Abstract: The renin-angiotensin system is upregulated with diabetes, and this may contribute to the development of a dilated myopathy. Angiotensin II (Ang II) locally may lead to oxidative damage, activating cardiac cell death. Moreover, diabetes and hypertension could synergistically impair myocardial structure and function. Therefore, apoptosis and necrosis were measured in ventricular myocardial biopsies obtained from diabetic and diabetic-hypertensive patients. Accumulation of a marker of oxidative stress, nitrotyrosine, and Ang II labeling were evaluated quantitatively. The diabetic heart showed cardiac hypertrophy, cavitary dilation, and depressed ventricular performance. These alterations were more severe with diabetes and hypertension. Diabetes was characterized by an 85-fold, 61-fold, and 26-fold increase in apoptosis of myocytes, endothelial cells, and fibroblasts, respectively. Apoptosis in cardiac cells did not increase additionally with diabetes and hypertension. Diabetes increased necrosis by 4-fold in myocytes, 9-fold in endothelial cells, and 6-fold in fibroblasts. However, diabetes and hypertension increased necrosis by 7-fold in myocytes and 18-fold in endothelial cells. Similarly, Ang II labeling in myocytes and endothelial cells increased more with diabetes and hypertension than with diabetes alone. Nitrotyrosine localization in cardiac cells followed a comparable pattern. In spite of the difference in the number of nitrotyrosine-positive cells with diabetes and with diabetes and hypertension, apoptosis and necrosis of myocytes, endothelial cells, and fibroblasts were detected only in cells containing this modified amino acid. In conclusion, local increases in Ang II with diabetes and with diabetes and hypertension may enhance oxidative damage, activating cardiac cell apoptosis and necrosis.

Oxidative Stress–Mediated Cardiac Cell Death Is a Major Determinant of Ventricular Dysfunction and Failure in Dog Dilated Cardiomyopathy

Abstract: Cell death has been questioned as a mechanism of ventricular failure. In this report, we tested the hypothesis that apoptotic death of myocytes, endothelial cells, and fibroblasts is implicated in ...

Nitric Oxide and Peroxynitrite in Health and Disease

Abstract: The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

Pluripotency of mesenchymal stem cells derived from adult marrow

Abstract: We report here that cells co-purifying with mesenchymal stem cells--termed here multipotent adult progenitor cells or MAPCs--differentiate, at the single cell level, not only into mesenchymal cells, but also cells with visceral mesoderm, neuroectoderm and endoderm characteristics in vitro. When injected into an early blastocyst, single MAPCs contribute to most, if not all, somatic cell types. On transplantation into a non-irradiated host, MAPCs engraft and differentiate to the haematopoietic lineage, in addition to the epithelium of liver, lung and gut. Engraftment in the haematopoietic system as well as the gastrointestinal tract is increased when MAPCs are transplanted in a minimally irradiated host. As MAPCs proliferate extensively without obvious senescence or loss of differentiation potential, they may be an ideal cell source for therapy of inherited or degenerative diseases.

Mesenchymal stem cells in health and disease

Abstract: Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal stem cells that can be isolated from many adult tissues. They can differentiate into cells of the mesodermal lineage, such as adipocytes, osteocytes and chondrocytes, as well as cells of other embryonic lineages. MSCs can interact with cells of both the innate and adaptive immune systems, leading to the modulation of several effector functions. After in vivo administration, MSCs induce peripheral tolerance and migrate to injured tissues, where they can inhibit the release of pro-inflammatory cytokines and promote the survival of damaged cells. This Review discusses the targets and mechanisms of MSC-mediated immunomodulation and the possible translation of MSCs to new therapeutic approaches.

Self-assembly and mineralization of peptide-amphiphile nanofibers

Abstract: We have used the pH-induced self-assembly of a peptide-amphiphile to make a nanostructured fibrous scaffold reminiscent of extracellular matrix. The design of this peptide-amphiphile allows the nanofibers to be reversibly cross-linked to enhance or decrease their structural integrity. After cross-linking, the fibers are able to direct mineralization of hydroxyapatite to form a composite material in which the crystallographic c axes of hydroxyapatite are aligned with the long axes of the fibers. This alignment is the same as that observed between collagen fibrils and hydroxyapatite crystals in bone.