scholarly journals Combined Analysis of Endothelial, Hematopoietic, and Mesenchymal Stem Cell Compartments Shows Simultaneous but Independent Effects of Age and Heart Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Carine Ghem ◽  
Lucinara Dadda Dias ◽  
Roberto Tofani Sant’Anna ◽  
Renato A. K. Kalil ◽  
Melissa Markoski ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Heart Disease ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Heart Diseases ◽  
Left Ventricular ◽  
Syntax Score ◽  
Hematopoietic Stem ◽  
Cell Compartments

Clinical trials using stem cell therapy for heart diseases have not reproduced the initial positive results obtained with animal models. This might be explained by a decreased regenerative capacity of stem cells collected from the patients. This work aimed at the simultaneous investigation of endothelial stem/progenitor cells (EPCs), mesenchymal stem/progenitor cells (MSCs), and hematopoietic stem/progenitor cells (HSCs) in sternal bone marrow samples of patients with ischemic or valvular heart disease, using flow cytometry and colony assays. The study included 36 patients referred for coronary artery bypass grafting or valve replacement surgery. A decreased frequency of stem cells was observed in both groups of patients. Left ventricular dysfunction, diabetes, and intermediate risk in EuroSCORE and SYNTAX score were associated with lower EPCs frequency, and the use of aspirin andβ-blockers correlated with a higher frequency of HSCs and EPCs, respectively. Most importantly, the distribution of frequencies in the three stem cell compartments showed independent patterns. The combined investigation of the three stem cell compartments in patients with cardiovascular diseases showed that they are independently affected by the disease, suggesting the investigation of prognostic factors that may be used to determine when autologous stem cells may be used in cell therapy.

scholarly journals Potential of cardiac stem/progenitor cells and induced pluripotent stem cells for cardiac repair in ischaemic heart disease

2013 ◽  
Vol 125 (7) ◽  
pp. 319-327 ◽  
Author(s):  
Wei Eric Wang ◽  
Xiongwen Chen ◽  
Steven R. Houser ◽  
Chunyu Zeng
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Heart Disease ◽  
Cell Therapy ◽  
Induced Pluripotent Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Autologous Transplantation ◽  
Cardiac Repair ◽  
Induced Pluripotent

Stem cell therapy has emerged as a promising strategy for cardiac and vascular repair. The ultimate goal is to rebuild functional myocardium by transplanting exogenous stem cells or by activating native stem cells to induce endogenous repair. CS/PCs (cardiac stem/progenitor cells) are one type of adult stem cell with the potential to differentiate into cardiac lineages (cardiomyocytes, smooth muscle cells and endothelial cells). iPSCs (induced pluripotent stem cells) also have the capacity to differentiate into necessary cells to rebuild injured cardiac tissue. Both types of stem cells have brought promise for cardiac repair. The present review summarizes recent advances in cardiac cell therapy based on these two cell sources and discusses the advantages and limitations of each candidate. We conclude that, although both types of stem cells can be considered for autologous transplantation with promising outcomes in animal models, CS/PCs have advanced more in their clinical application because iPSCs and their derivatives possess inherent obstacles for clinical use. Further studies are needed to move cell therapy forward for the treatment of heart disease.

scholarly journals Current status, challenges and perspectives of mesenchymal stem cell-based therapy for cardiac regeneration

2021 ◽  
Vol 10 (3) ◽  
pp. 72-78
Author(s):  
P. M. Docshin ◽  
A. Bairqdar ◽  
A. B. Malashicheva
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Side Population ◽  
Heart Diseases ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Individual Characteristics ◽  
Current Status ◽  
Cell Based Therapy

Modern methods of treating heart failure are similar to the palliative care, since they mostly relieve the symptoms of the disease. The discovery of resident cardiac stem cells gave impetus to the development of “second generation” cell therapy, which quickly moved from animal research to clinical trials with critically ill patients. Many cardiac side population cells have been identified to have stem cells characteristics and some additional individual characteristics, both in vitro and in vivo. The results of clinical studies demonstrated that the stem cell treatment is safe, however, this type of cell-based therapy did not restore cardiac function. Its effects were limited to mildly improving left ventricular systolic pressure and reducing the scar area. Despite that, the promising nature of these therapeutic approaches for heart diseases have contributed to the development of next-generation cell therapy.

New Aspects of Cell Therapy for Iscemic Heart Disease (Review)

2015 ◽  
Vol 22 (3) ◽  
pp. 165-171
Author(s):  
Рейдман ◽  
V. Reydman ◽  
Кравченко ◽  
T. Kravchenko ◽  
Козель ◽  
...  
Keyword(s):  
Stem Cells ◽  
Heart Disease ◽  
Cell Therapy ◽  
Ischemic Heart Disease ◽  
Progenitor Cells ◽  
Laser Irradiation ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Long Term Results ◽  
Left Ventricular Ejection

The authors reviewed the modern methods of cell therapy for ischemic heart disease. The experimental and clinical researches demonstrated that transplantation of hematopoietic progenitor cells and mesenchymal stem cells contributes to reduction of the postinfarction scar size, to increase of left ventricular ejection fraction, to decrease of cardiac remodeling, resulting in the reduction of end-diastolic and end-systolic volumes. This treatment promoted an increase of exercise tolerance, decrease of angina functional class and improved the quality of life. The best long-term results were observed for the early beginning of cell therapy and the implantation of cells directly into the myocardium. The cultures of resident cardiomyocyte progenitor cells significantly improved the results of treatment. Hypoxic preconditioning or low intensity laser irradiation enhanced the therapeutic potential of the cells cultured for transplantation, activated proliferation and reduced apoptosis. Good results were achieved with laser revascularization of myocardium before the cell transplantation. New non-invasive methods of treatment for ischemic heart disease, based on the increase in the concentration of stem cells in peripheral blood with G-CSF application or laser irradiation of the bone marrow localization areas were suggested.

scholarly journals Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
S. Sakinah ◽  
Sivan Padma Priya ◽  
Pooi Ling Mok ◽  
Rusheni Munisvaradass ◽  
Seoh Wei Teh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mouse Model ◽  
Cell Therapy ◽  
Dengue Virus ◽  
Progenitor Cells ◽  
Stem Cell Therapy ◽  
Dengue Infection ◽  
Target Cells ◽  
Hematopoietic Stem

Extensive clinical efforts have been made to control the severity of dengue diseases; however, the dengue morbidity and mortality have not declined. Dengue virus (DENV) can infect and cause systemic damage in many organs, resulting in organ failure. Here, we present a novel report showing a tailored stem-cell-based therapy that can aid in viral clearance and rescue liver cells from further damage during dengue infection. We administered a combination of hematopoietic stem cells and endothelial progenitor cells in a DENV-infected BALB/c mouse model and found that delivery of this cell cocktail had improved their liver functions, confirmed by hematology, histopathology, and next-generation sequencing. These stem and progenitor cells can differentiate into target cells and repair the damaged tissues. In addition, the regime can regulate endothelial proliferation and permeability, modulate inflammatory reactions, enhance extracellular matrix production and angiogenesis, and secrete an array of growth factors to create an enhanced milieu for cell reparation. No previous study has been published on the treatment of dengue infection using stem cells combination. In conclusion, dengue-induced liver damage was rescued by administration of stem cell therapy, with less apoptosis and improved repair and regeneration in the dengue mouse model.

scholarly journals Stem cells in the treatment of patients with coronary heart disease. Part I

2011 ◽  
Vol 10 (2) ◽  
pp. 122-128 ◽  
Author(s):  
N. S. Zhukova ◽  
I. I. Staroverov
Keyword(s):  
Stem Cells ◽  
Coronary Heart Disease ◽  
Stem Cell ◽  
Heart Disease ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Myocardial Damage ◽  
Cellular Cardiomyoplasty ◽  
Modern Methods ◽  
Death Causes

Heart failure (HF) is one of the leading death causes in patients with myocardial infarction (MI). The modern methods of reperfusion MI therapy, such as thrombolysis, surgery and balloon revascularization, even when performed early, could fail to prevent the development of large myocardial damage zones, followed by HF. Therefore, the researches have been searching for the methods which improve functional status of damaged myocardium. This review is focused on stem cell therapy, a method aimed at cardiac function restoration. The results of experimental and clinical studies on stem cell therapy in coronary heart disease are presented. Various types of stem cells, used for cellular cardiomyoplasty, are characterised. The methods of cell transplantation into myocardium and potential adverse effects of stem cell therapy are discussed.

scholarly journals Very Small Embryonic-Like Stem Cells, Endothelial Progenitor Cells, and Different Monocyte Subsets Are Effectively Mobilized in Acute Lymphoblastic Leukemia Patients after G-CSF Treatment

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Andrzej Eljaszewicz ◽  
Lukasz Bolkun ◽  
Kamil Grubczak ◽  
Malgorzata Rusak ◽  
Tomasz Wasiluk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Lymphoblastic Leukemia ◽  
Monocyte Subsets ◽  
Endothelial Progenitor ◽  
Hematopoietic Stem ◽  
Cd34 Cells

Background. Acute lymphoblastic leukemia (ALL) is a malignant disease of lymphoid progenitor cells. ALL chemotherapy is associated with numerous side effects including neutropenia that is routinely prevented by the administration of growth factors such as granulocyte colony-stimulating factor (G-CSF). To date, the effects of G-CSF treatment on the level of mobilization of different stem and progenitor cells in ALL patients subjected to clinically effective chemotherapy have not been fully elucidated. Therefore, in this study we aimed to assess the effect of administration of G-CSF to ALL patients on mobilization of other than hematopoietic stem cell (HSCs) subsets, namely, very small embryonic-like stem cells (VSELs), endothelial progenitor cells (EPCs), and different monocyte subsets. Methods. We used multicolor flow cytometry to quantitate numbers of CD34+ cells, hematopoietic stem cells (HSCs), VSELs, EPCs, and different monocyte subsets in the peripheral blood of ALL patients and normal age-matched blood donors. Results. We showed that ALL patients following chemotherapy, when compared to healthy donors, presented with significantly lower numbers of CD34+ cells, HSCs, VSELs, and CD14+ monocytes, but not EPCs. Moreover, we found that G-CSF administration induced effective mobilization of all the abovementioned progenitor and stem cell subsets with high regenerative and proangiogenic potential. Conclusion. These findings contribute to better understanding the beneficial clinical effect of G-CSF administration in ALL patients following successful chemotherapy.

scholarly journals Intestinal myofibroblasts: targets for stem cell therapy

2011 ◽  
Vol 300 (5) ◽  
pp. G684-G696 ◽  
Author(s):  
R. C. Mifflin ◽  
I. V. Pinchuk ◽  
J. I. Saada ◽  
D. W. Powell
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Stem Cell ◽  
Cell Therapy ◽  
Lamina Propria ◽  
Stem Cell Therapy ◽  
Intestinal Inflammation ◽  
Mesenchymal Cells ◽  
Hematopoietic Stem ◽  
Intestinal Lamina Propria

The subepithelial intestinal myofibroblast is an important cell orchestrating many diverse functions in the intestine and is involved in growth and repair, tumorigenesis, inflammation, and fibrosis. The myofibroblast is but one of several α-smooth muscle actin-positive (α-SMA+) mesenchymal cells present within the intestinal lamina propria, including vascular pericytes, bone marrow-derived stem cells (mesenchymal stem cells or hematopoietic stem cells), muscularis mucosae, and the lymphatic pericytes (colon) and organized smooth muscle (small intestine) associated with the lymphatic lacteals. These other mesenchymal cells perform many of the functions previously attributed to subepithelial myofibroblasts. This review discusses the definition of a myofibroblast and reconsiders whether the α-SMA+ subepithelial cells in the intestine are myofibroblasts or other types of mesenchymal cells, i.e., pericytes. Current information about specific, or not so specific, molecular markers of lamina propria mesenchymal cells is reviewed, as well as the origins of intestinal myofibroblasts and pericytes in the intestinal lamina propria and their replenishment after injury. Current concepts and research on stem cell therapy for intestinal inflammation are summarized. Information about the stem cell origin of intestinal stromal cells may inform future stem cell therapies to treat human inflammatory bowel disease (IBD).

scholarly journals Hematopoietic stem cells in the blood after stem cell factor and interleukin-11 administration: evidence for different mechanisms of mobilization

Blood ◽  
1995 ◽  
Vol 86 (12) ◽  
pp. 4674-4680 ◽  
Author(s):  
P Mauch ◽  
C Lamont ◽  
TY Neben ◽  
C Quinto ◽  
SJ Goldman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Stem Cell Factor ◽  
Cytotoxic Agents ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Blood Stem Cells ◽  
Interleukin 11

Peripheral blood stem cells and progenitor cells, collected during recovery from exposure to cytotoxic agents or after cytokine administration, are being increasingly used in clinical bone marrow transplantation. To determine factors important for mobilization of both primitive stem cells and progenitor cells to the blood, we studied the blood and splenic and marrow compartments of intact and splenectomized mice after administration of recombinant human interleukin-11 (rhlL-11), recombinant rat stem cell factor (rrSCF), and IL-11 + SCF. IL-11 administration increased the number of spleen colony- forming units (CFU-S) in both the spleen and blood, but did not increase blood long-term marrow-repopulating ability (LTRA) in intact or splenectomized mice. SCF administration increased the number of CFU- S in both the spleen and blood and did not increase the blood or splenic LTRA of intact mice, but did increase blood LTRA to normal marrow levels in splenectomized mice. The combination of lL-11 + SCF syngeristically enhanced mobilization of long-term marrow-repopulating cells from the marrow to the spleen of intact mice and from the marrow to the blood of splenectomized mice. These data, combined with those of prior studies showing granulocyte colony-stimulating factor mobilization of long-term marrow repopulating cells from the marrow to the blood of mice with intact spleens, suggest different cytokine- induced pathways for mobilization of primitive stem cells.

scholarly journals Regenerative Cardiovascular Therapies: Stem Cells and Beyond

2019 ◽  
Vol 20 (6) ◽  
pp. 1420 ◽  
Author(s):  
Bernhard Wernly ◽  
Moritz Mirna ◽  
Richard Rezar ◽  
Christine Prodinger ◽  
Christian Jung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Basic Science ◽  
Left Ventricular ◽  
Specific Cell ◽  
Therapeutic Effects ◽  
Cell Processing

Although reperfusion therapy has improved outcomes, acute myocardial infarction (AMI) is still associated with both significant mortality and morbidity. Once irreversible myocardial cell death due to ischemia and reperfusion sets in, scarring leads to reduction in left ventricular function and subsequent heart failure. Regenerative cardiovascular medicine experienced a boost in the early 2000s when regenerative effects of bone marrow stem cells in a murine model of AMI were described. Translation from an animal model to stem cell application in a clinical setting was rapid and the first large trials in humans suffering from AMI were conducted. However, high initial hopes were early shattered by inconsistent results of randomized clinical trials in patients suffering from AMI treated with stem cells. Hence, we provide an overview of both basic science and clinical trials carried out in regenerative cardiovascular therapies. Possible pitfalls in specific cell processing techniques and trial design are discussed as these factors influence both basic science and clinical outcomes. We address possible solutions. Alternative mechanisms and explanations for effects seen in both basic science and some clinical trials are discussed here, with special emphasis on paracrine mechanisms via growth factors, exosomes, and microRNAs. Based on these findings, we propose an outlook in which stem cell therapy, or therapeutic effects associated with stem cell therapy, such as paracrine mechanisms, might play an important role in the future. Optimizing stem cell processing and a better understanding of paracrine signaling as well as its effect on cardioprotection and remodeling after AMI might improve not only AMI research, but also our patients’ outcomes.

Differential Role for VLA-5 in Mobilization of Heamotopoieic Stem Cells Toward Peripheral Blood and Homing to Bone Marrow and Spleen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2190-2190 ◽  
Author(s):  
Pieter K. Wierenga ◽  
Ellen Weersing ◽  
Bert Dontje ◽  
Gerald de Haan ◽  
Ronald P. van Os
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Hematopoietic Stem ◽  
Late Antigen ◽  
Cell Mobilization

Abstract Adhesion molecules have been implicated in the interactions of hematopoietic stem and progenitor cells with the bone marrow extracellular matrix and stromal cells. In this study we examined the role of very late antigen-5 (VLA-5) in the process of stem cell mobilization and homing after stem cell transplantation. In normal bone marrow (BM) from CBA/H mice 79±3 % of the cells in the lineage negative fraction express VLA-5. After mobilization with cyclophosphamide/G-CSF, the number of VLA-5 expressing cells in mobilized peripheral blood cells (MPB) decreases to 36±4%. The lineage negative fraction of MPB cells migrating in vitro towards SDF-1α (M-MPB) demonstrated a further decrease to 3±1% of VLA-5 expressing cells. These data are suggestive for a downregulation of VLA-5 on hematopoietic cells during mobilization. Next, MPB cells were labelled with PKH67-GL and transplanted in lethally irradiated recipients. Three hours after transplantation an increase in VLA-5 expressing cells was observed which remained stable until 24 hours post-transplant. When MPB cells were used the percentage PKH-67GL+ Lin− VLA-5+ cells increased from 36% to 88±4%. In the case of M-MPB cells the number increased from 3% to 33±5%. Although the increase might implicate an upregulation of VLA-5, we could not exclude selective homing of VLA-5+ cells as a possible explanation. Moreover, we determined the percentage of VLA-5 expressing cells immediately after transplantation in the peripheral blood of the recipients and were not able to observe any increase in VLA-5+ cells in the first three hours post-tranpslant. Finally, we separated the MPB cells in VLA-5+ and VLA-5− cells and plated these cells out in clonogenic assays for progenitor (CFU-GM) and stem cells (CAFC-day35). It could be demonstared that 98.8±0.5% of the progenitor cells and 99.4±0.7% of the stem cells were present in the VLA-5+ fraction. Hence, VLA-5 is not downregulated during the process of mobilization and the observed increase in VLA-5 expressing cells after transplantation is indeed caused by selective homing of VLA-5+ cells. To shed more light on the role of VLA-5 in the process of homing, BM and MPB cells were treated with an antibody to VLA-5. After VLA-5 blocking of MPB cells an inhibition of 59±7% in the homing of progenitor cells in bone marrow could be found, whereas homing of these subsets in the spleen of the recipients was only inhibited by 11±4%. For BM cells an inhibition of 60±12% in the bone marrow was observed. Homing of BM cells in the spleen was not affected at all after VLA-5 blocking. Based on these data we conclude that mobilization of hematopoietic progenitor/stem cells does not coincide with a downregulation of VLA-5. The observed increase in VLA-5 expressing cells after transplantation is caused by preferential homing of VLA-5+ cells. Homing of progenitor/stem cells to the bone marrow after transplantation apparantly requires adhesion interactions that can be inhibited by blocking VLA-5 expression. Homing to the spleen seems to be independent of VLA-5 expression. These data are indicative for different adhesive pathways in the process of homing to bone marrow or spleen.

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