Innovation in Basic Science: Stem Cells and their role in the treatment of Paediatric Cardiac Failure – Opportunities and Challenges

2009 ◽  
Vol 19 (S2) ◽  
pp. 74-84 ◽  
Author(s):  
Sunjay Kaushal ◽  
Jeffrey Phillip Jacobs ◽  
Jeffrey G. Gossett ◽  
Ann Steele ◽  
Peter Steele ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Embryonic Stem Cells ◽  
Cardiac Failure ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cardiac Regeneration ◽  
Cardiac Progenitor Cells ◽  
Cardiac Stem Cells ◽  
Skeletal Myoblasts

AbstractHeart failure is a leading cause of death worldwide. Current therapies only delay progression of the cardiac disease or replace the diseased heart with cardiac transplantation. Stem cells represent a recently discovered novel approach to the treatment of cardiac failure that may facilitate the replacement of diseased cardiac tissue and subsequently lead to improved cardiac function and cardiac regeneration.A stem cell is defined as a cell with the properties of being clonogenic, self-renewing, and multipotent. In response to intercellular signalling or environmental stimuli, stem cells differentiate into cells derived from any of the three primary germ layers: ectoderm, endoderm, and mesoderm, a powerful advantage for regenerative therapies. Meanwhile, a cardiac progenitor cell is a multipotent cell that can differentiate into cells of any of the cardiac lineages, including endothelial cells and cardiomyocytes.Stem cells can be classified into three categories: (1) adult stem cells, (2) embryonic stem cells, and (3) induced pluripotential cells. Adult stem cells have been identified in numerous organs and tissues in adults, including bone-marrow, skeletal muscle, adipose tissue, and, as was recently discovered, the heart. Embryonic stem cells are derived from the inner cell mass of the blastocyst stage of the developing embryo. Finally through transcriptional reprogramming, somatic cells, such as fibroblasts, can be converted into induced pluripotential cells that resemble embryonic stem cells.Four classes of stem cells that may lead to cardiac regeneration are: (1) Embryonic stem cells, (2) Bone Marrow derived stem cells, (3) Skeletal myoblasts, and (4) Cardiac stem cells and cardiac progenitor cells. Embryonic stem cells are problematic because of several reasons: (1) the formation of teratomas, (2) potential immunologic cellular rejection, (3) low efficiency of their differentiation into cardiomyocytes, typically 1% in culture, and (4) ethical and political issues. As of now, bone marrow derived stem cells have not been proven to differentiate reproducibly and reliably into cardiomyocytes. Skeletal myoblasts have created in vivo myotubes but have not electrically integrated with the myocardium. Cardiac stem cells and cardiac progenitor cells represent one of the most promising types of cellular therapy for children with cardiac failure.

scholarly journals Stem Cell Repair for Cardiac Muscle Regeneration: A Review of the Literature

2016 ◽  
Vol 4 (1) ◽  
pp. 19-25
Author(s):  
Georgiana Farrugia ◽  
Rena Balzan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Side Population ◽  
Embryonic Stem ◽  
Cardiac Progenitor Cells ◽  
Cardiac Stem Cells ◽  
Skeletal Myoblasts ◽  
Islet 1

The notion that the human adult heart is a quiescent organ incapable of self-regeneration has been successfully challenged. It is now evident that the heart possesses a significant ability for repair and regeneration. Stem cells of endogenous cardiac origin are currently considered to possess the greatest ability to differentiate into cardiomyocytes. The major types of cardiac stem cells that show a promising potential to replace damaged cardiomyocytes include C-KIT positive (C-KIT+) cardiac progenitor cells, cardiosphere-derived progenitor cells, islet-1 (Isl1+) cardiac progenitor cells, side-population cardiac progenitor cells, epicardium-derived progenitor cells and stem cell antigen-1 (SCA1+) cardiac progenitor cells. Moreover, stem cells of extra-cardiac origin are also thought to restore contractility and vascularization of the myocardium. These include skeletal myoblasts, bone marrow mononuclear cells, mesenchymal stem cells, endothelial progenitor cells as well as embryonic stem cells. The need for further investigation on cardiac stem cell therapeutic strategies still remains.

Abstract 241: Cardiac TIMP-4 Dictates cardiomyocyte contractility and differentiation of embryonic stem cells into cardiomyocytes: Road to Therapy

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Pankaj Chaturvedi ◽  
Anuradha Kalani ◽  
Anastasia Familtseva ◽  
Pradip K Kamat ◽  
Naira Metriveli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Progenitor Cells ◽  
Embryonic Stem ◽  
Cardiac Regeneration ◽  
Matrix Metalloproteases ◽  
Cardiac Progenitor Cells ◽  
Cardiac Phenotype ◽  
Cardiomyocyte Contractility ◽  
Ros Scavenger

The remarkable nature of cardiomyocytes for contractility is attributed to the extracellular matrix which is maintained by the balance between MMPs (Matrix Metalloproteases) and TIMPs (Tissue Inhibitors of Matrix Metalloproteases). Any deviation from this delicate balance of MMP/TIMP is a hallmark of cardiovascular pathologies including myocardial infarction (MI). TIMP4, which is the least studied molecule, is deficient in failing hearts and mice lacking TIMP4 show poor regeneration capacity after MI. Therefore, we hypothesize that TIMP4 helps in cardiac regeneration by alleviating contractility and inducing the differentiation of cardiac progenitor cells into cardiomyocytes. To validate this hypothesis, we transfected cardiomyocytes with TIMP4 and TIMP4-siRNA and observed that there was increase in contractility in the TIMP4 transfected cardiomyocytes as compared to siRNA-TIMP4 transfected cardiomyocytes. To explain this we looked into the calcium channel genes and found increase in the expression of serca2a (sarcoplasmic reticulum calcium ATPase2a) in the TIMP4 transformed myocytes. Serca2a is tightly regulated by mir122a and we found decrease in the expression of mir122a in the TIMP4 transfected cells as compared to the TIMP4-siRNA cells. To observe the effect of TIMP4 in differentiation of cardiac progenitor cells we treated mouse embryonic stem cells with cardiac extract and cardiac extract minus TIMP4 (using TIMP4 monoclonal antibody). The cells treated with cardiac extract showed cardiac phenotype in terms of Ckit+, GATA4+ and Nkx2.5 expression. This is a novel report on the influence of TIMP4 on contractility and inducing the differentiation of stem cells to cardiomyocytes. In view of the failure of MMP9 inhibitors for cardiac therapy in clinical trials, TIMP4 provides and alternative approach, being an indigenous molecule, a natural inhibitor of MMP9 and efficient ROS scavenger.

Differential bone-forming capacity of osteogenic cells from either embryonic stem cells or bone marrow-derived mesenchymal stem cells

2010 ◽  
Vol 5 (3) ◽  
pp. 180-190 ◽  
Author(s):  
Sanne K. Both ◽  
Aart A. van Apeldoorn ◽  
Jojanneke M. Jukes ◽  
Mikael C.O. Englund ◽  
Johan Hyllner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Osteogenic Cells

Types of Stem Cells Used in US-Based Clinical Trials between 1999 and 2014

2021 ◽  
Vol 26 ◽  
pp. 169-191
Author(s):  
Emma E. Redfield ◽  
Erin K. Luciano ◽  
Monica J. Sewell ◽  
Lucas A. Mitzel ◽  
Isaac J. Sanford ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
The Us ◽  
Health Database ◽  
Induced Pluripotent

This study looks at the number of clinical trials involving specific stem cell types. To our knowledge, this has never been done before. Stem cell clinical trials that were conducted at locations in the US and registered on the National Institutes of Health database at ‘clinicaltrials.gov’ were categorized according to the type of stem cell used (adult, cancer, embryonic, perinatal, or induced pluripotent) and the year that the trial was registered. From 1999 to 2014, there were 2,357 US stem cell clinical trials registered on ‘clinicaltrials.gov,’ and 89 percent were from adult stem cells and only 0.12 percent were from embryonic stem cells. This study concludes that embryonic stem cells should no longer be used for clinical study because of their irrelevance, moral questions, and induced pluripotent stem cells.

Magnetic resonance tracking of transplanted bone marrow and embryonic stem cells labeled by iron oxide nanoparticles in rat brain and spinal cord

2004 ◽  
Vol 76 (2) ◽  
pp. 232-243 ◽  
Author(s):  
Pavla Jendelová ◽  
Vít Herynek ◽  
Lucia Urdzíková ◽  
Kateřina Glogarová ◽  
Jana Kroupová ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Iron Oxide ◽  
Embryonic Stem Cells ◽  
Magnetic Resonance ◽  
Rat Brain ◽  
Embryonic Stem ◽  
Oxide Nanoparticles ◽  
Brain And Spinal Cord

scholarly journals Cardiac Regeneration After Myocardial Infarction: an Approachable Goal

2020 ◽  
Vol 22 (10) ◽  
Author(s):  
Mauro Giacca
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Adult Stem Cells ◽  
Ex Vivo ◽  
Embryonic Stem ◽  
Cardiac Regeneration ◽  
Myocardial Tissue ◽  
Induced Pluripotent ◽  
Large Animals

Abstract Purpose of Review Until recently, cardiac regeneration after myocardial infarction has remained a holy grail in cardiology. Failure of clinical trials using adult stem cells and scepticism about the actual existence of such cells has reinforced the notion that the heart is an irreversibly post-mitotic organ. Recent evidence has drastically challenged this conclusion. Recent Findings Cardiac regeneration can successfully be obtained by at least two strategies. First, new cardiomyocytes can be generated from embryonic stem cells or induced pluripotent stem cells and administered to the heart either as cell suspensions or upon ex vivo generation of contractile myocardial tissue. Alternatively, the endogenous capacity of cardiomyocytes to proliferate can be stimulated by the delivery of individual genes or, more successfully, of selected microRNAs. Summary Recent experimental success in large animals by both strategies now fuels the notion that cardiac regeneration is indeed possible. Several technical hurdles, however, still need to be addressed and solved before broad and successful clinical application is achieved.

Derivation of SSEA4-/CD73+ Mesenchymal Stem Cells from Human Embryonic Stem Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2579-2579
Author(s):  
Parul Trivedi ◽  
Peiman Hematti
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Clinical Applications ◽  
Differentiation Potential ◽  
Hla Class I Antigens ◽  
Undifferentiated Hescs

Abstract Human embryonic stem cells (hESCs) could potentially provide a renewable source of different types of cells for cell therapy applications. Recently, mesenchymal stem cells (MSCs) have been derived from hESCs either through co-culturing with murine OP9 bone marrow stromal cell line or directly from hESCs without co-culturing with OP9 cells. Although the latter methodology is clinically advantageous over co-culturing with an animal cell layer those mesenchymal cells were reported to be positive for SSEA4. SSEA4 is a marker of undifferentiated hESCs and thus the presence of this marker on hESC-derived cells could potentially be problematic for clinical applications. We have recently achieved a novel and reproducible methodology for deriving a pure population of SSEA4-/CD73+ MSCs from federally approved hESC lines H1 and H9. To initiate the differentiation of hESCs to MSCs, we cultured undifferentiated hESCs on matrigel plates in murine embryonic fibroblast conditioned media with media changes every 3 days. Under these culture conditions a portion of embryonic stem cells differentiated into fibroblast looking cells. Through a multi-step process which involved the use of a culture methodology similar to what is being used to culture bone marrow (BM)-derived MSCs, and passaging cultured cells at defined time points we were able to derive a pure population of cells that were uniformly positive for MSC marker CD73 in about a 4-weeks period. These cells had fibroblast/mesenchymal looking morphology, and expressed cell surface marker antigens similar to what has been reported for adult human BM-derived MSCs: they are positive for CD29, CD44, CD54, CD71, CD90, glycophorin A, CD105, and were negative for hematopoietic markers such as CD34 and CD45. Similar to adult BM-derived MSCs these cells express HLA class-I antigens but not class-II antigens. Using established differentiation protocols we could differentiate the hESC-derived CD73+ MSCs into adipocytes, osteocytes, and chondrocytes as verified by immunohistochemistry and RT-PCR assays. So far we have grown these CD73+ MSCs up to passages 15–18. These cells retained their differentiation potential, and were karotypically normal when tested at passage 12. Most importantly, we did not observe any MSCs that were double positive for CD73 and SSEA4 antigen at any time point during our experiments. MSCs from a variety of fetal and adult sources are in various stages of clinical trials with some encouraging preliminary results. Our hESC-derived MSCs that are very similar to adult BM-derived MSCs regarding their growth and morphologic properties, immunophenotypic characteristics, differentiation potential, and importantly are devoid of hESC marker SSEA4 could potentially provide a novel source of MSCs for clinical applications.

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