scholarly journals Recent Progress in Stem Cell Modification for Cardiac Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-22 ◽  
Author(s):  
Heiko Lemcke ◽  
Natalia Voronina ◽  
Gustav Steinhoff ◽  
Robert David

During the past decades, stem cell-based therapy has acquired a promising role in regenerative medicine. The application of novel cell therapeutics for the treatment of cardiovascular diseases could potentially achieve the ambitious aim of effective cardiac regeneration. Despite the highly positive results from preclinical studies, data from phase I/II clinical trials are inconsistent and the improvement of cardiac remodeling and heart performance was found to be quite limited. The major issues which cardiac stem cell therapy is facing include inefficient cell delivery to the site of injury, accompanied by low cell retention and weak effectiveness of remaining stem cells in tissue regeneration. According to preclinical and clinical studies, various stem cells (adult stem cells, embryonic stem cells, and induced pluripotent stem cells) represent the most promising cell types so far. Beside the selection of the appropriate cell type, researchers have developed several strategies to produce “second-generation” stem cell products with improved regenerative capacity. Genetic and nongenetic modifications, chemical and physical preconditioning, and the application of biomaterials were found to significantly enhance the regenerative capacity of transplanted stem cells. In this review, we will give an overview of the recent developments in stem cell engineering with the goal to facilitate stem cell delivery and to promote their cardiac regenerative activity.

2021 ◽  
Vol 26 ◽  
pp. 169-191
Author(s):  
Emma E. Redfield ◽  
Erin K. Luciano ◽  
Monica J. Sewell ◽  
Lucas A. Mitzel ◽  
Isaac J. Sanford ◽  
...  

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.


2009 ◽  
Vol 58 (4) ◽  
pp. 301-308 ◽  
Author(s):  
Cristina A. Szigyarto ◽  
Paul Sibbons ◽  
Gill Williams ◽  
Mathias Uhlen ◽  
Su M. Metcalfe

Axotrophin/MARCH-7 was first identified in mouse embryonic stem cells as a neural stem cell gene. Using the axotrophin/MARCH-7 null mouse, we discovered profound effects on T lymphocyte responses, including 8-fold hyperproliferation and 5-fold excess release of the stem cell cytokine leukemia inhibitory factor (LIF). Our further discovery that axotrophin/MARCH-7 is required for targeted degradation of the LIF receptor subunit gp190 implies a direct role in the regulation of LIF signaling. Bioinformatics studies revealed a highly conserved RING-CH domain in common with the MARCH family of E3-ubiquitin ligases, and accordingly, axotrophin was renamed “MARCH-7.” To probe protein expression of human axotrophin/MARCH-7, we prepared antibodies against different domains of the protein. Each antibody bound its specific target epitope with high affinity, and immunohistochemistry cross-validated target specificity. Forty-eight human tissue types were screened. Epithelial cells stained strongly, with trophoblasts having the greatest staining. In certain tissues, specific cell types were selectively positive, including neurons and neuronal progenitor cells in the hippocampus and cerebellum, endothelial sinusoids of the spleen, megakaryocytes in the bone marrow, crypt stem cells of the small intestine, and alveolar macrophages in the lung. Approximately 20% of central nervous system neuropils were positive. Notably, axotrophin/MARCH-7 has an expression profile that is distinct from that of other MARCH family members. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.


Author(s):  
Nidhi Puranik ◽  
Ananta Prasad Arukha ◽  
Shiv Kumar Yadav ◽  
Dhananjay Yadav ◽  
Jun O Jin

: Several human neurological disorders such as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis; Huntington’s disease, spinal cord injury, multiple sclerosis, and brain stroke, are caused by the injury to neurons or glial cells. The recent years have witnessed the successful generation of neurons and glia cells driving efforts to develop stem-cell-based therapies for patients to combat a broad spectrum of human neurological diseases. The inadequacy of suitable cell types for cell replacement therapy in patients suffering from neurological disorders have hampered the development of this promising therapeutic approach. Attempts are thus being made to reconstruct viable neurons and glial cells from different stem cells such as the embryonic stem cells, mesenchymal stem cells, and neural stem cells. Dedicated research to cultivate stem cell-based brain transplantation therapies have been carried out. We aim at compiling the breakthroughs in the field of stem cell-based therapy for the treatment of neurodegenerative maladies, emphasizing on the shortcomings faced, victories achieved, and the future prospects of the therapy in clinical settings.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Maria G. Roubelakis ◽  
Ourania Trohatou ◽  
Nicholas P. Anagnou

Amniotic fluid (AF) and amniotic membrane (AM) have been recently characterized as promising sources of stem or progenitor cells. Both not only contain subpopulations with stem cell characteristics resembling to adult stem cells, such as mesenchymal stem cells, but also exhibit some embryonic stem cell properties like (i) expression of pluripotency markers, (ii) high expansion in vitro, or (iii) multilineage differentiation capacity. Recent efforts have been focused on the isolation and the detailed characterization of these stem cell types. However, variations in their phenotype, their heterogeneity described by different groups, and the absence of a single marker expressed only in these cells may prevent the isolation of a pure homogeneous stem cell population from these sources and their potential use of these cells in therapeutic applications. In this paper, we aim to summarize the recent progress in marker discovery for stem cells derived from fetal sources such as AF and AM, using novel methodologies based on transcriptomics, proteomics, or secretome analyses.


2004 ◽  
pp. U7-12 ◽  
Author(s):  
C Mummery

Stem cell research holds the promise of treatments for many disorders resulting from disease or trauma where one or at most a few cell types have been lost or do not function. In combination with tissue engineering, stem cells may represent the greatest contribution to contemporary medicine of the present century. Progress is however being hampered by the debate on the origin of stem cells, which can be derived from human embryos and some adult tissues. Politics, religious beliefs and the media have determined society's current perception of their relative value while the ethical antipathy towards embryonic stem cells, which require destruction of a human embryo for their derivation, has in many countries biased research towards adult stem cells. Many scientists believe this bias may be premature and basic research on both cell types is still required. The media has created confusion about the purpose of stem cell research: treating chronic ailments or striving for immortality. Here, the scientific state of the art on adult and embryonic stem cells is reviewed as a basis for a debate on whether research on embryonic stem cells is ethically acceptable.


2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Calvin C. Sheng ◽  
Li Zhou ◽  
Jijun Hao

Heart failure commonly results from an irreparable damage due to cardiovascular diseases (CVDs), the leading cause of morbidity and mortality in the United States. In recent years, the rapid advancements in stem cell research have garnered much praise for paving the way to novel therapies in reversing myocardial injuries. Cell types currently investigated for cellular delivery include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cell lineages such as skeletal myoblasts, bone-marrow-derived stem cells (BMSCs), mesenchymal stem cells (MSCs), and cardiac stem cells (CSCs). To engraft these cells into patients’ damaged myocardium, a variety of approaches (intramyocardial, transendocardial, transcoronary, venous, intravenous, intracoronary artery and retrograde venous administrations and bioengineered tissue transplantation) have been developed and explored. In this paper, we will discuss the pros and cons of these delivery modalities, the current state of their therapeutic potentials, and a multifaceted evaluation of their reported clinical feasibility, safety, and efficacy. While the issues of optimal delivery approach, the best progenitor stem cell type, the most effective dose, and timing of administration remain to be addressed, we are highly optimistic that stem cell therapy will provide a clinically viable option for myocardial regeneration.


2006 ◽  
Vol 18 (8) ◽  
pp. 829 ◽  
Author(s):  
Barry D. Bavister

The distribution and functions of mitochondria in stem cells have not been examined, yet the contributions of these organelles to stem cell viability and differentiation must be vitally important in view of their critical roles in all other cell types. A key role for mitochondria in stem cells is indicated by reports that they translocate in the oocyte during fertilisation to cluster around the pronuclei and can remain in a perinuclear pattern during embryo development. This clustering appears to be essential for normal embryonic development. Because embryonic stem cells are derived from fertilised oocytes, and eventually can differentiate into ‘adult’ stem cells, it was hypothesised that mitochondrial perinuclear clustering persists through preimplantation embryo development into the stem cells, and that this localisation is indicative of stem cell pluripotency. Further, it was predicted that mitochondrial activity, as measured by respiration and adenosine triphosphate (ATP) content, would correlate with the degree of perinuclear clustering. It was also predicted that these morphological and metabolic measurements could serve as indicators of ‘stemness.’ This article reviews the distribution and metabolism of mitochondria in a model stem cell line and how this information is related to passage number, differentiation and/or senescence. In addition, it describes mitochondrial DNA deletions in oocytes and embryos that could adversely affect stem cell performance.


Author(s):  
Franz Ricklefs ◽  
Sonja Schrepfer

Current medical research is focused on two particular types of stem cells, adult stem cells and embryonic stem cells. Both cell types demonstrate a tremendous potential as the source for regenerative medicine due to their paracrine and pluripotency effects, respectively. Therefore, stem cells are expected to have an enormous impact on clinical therapy. However, allogeneic approaches using “off-the-shelf” stem cells from healthy donors are the only financially and ethically feasible pathway. The long-standing assumption that stem cells are not recognized by the recipient’s immune system was recently disproved not only by our group. Therefore, specific knowledge of the immunologic properties of pluripotent and multipotent stem cells is a prerequisite for safe applications of stem cell-based therapy. This chapter will discuss the involvement of the innate and adaptive immune system and summarize state-of-the art approaches to overcome the immunological barrier.


2021 ◽  
Vol 2 ◽  
pp. 2
Author(s):  
Vikash Chandra ◽  
Mudasir Bashir Gugjoo ◽  
Amarpal ◽  
G. Taru Sharma

Stem cells are wonder cells that function silently in an individual to grow and/to regenerate. There are various stem cell types; some especially embryonic stem cells (ESCs) favor individual development while more advanced cells like adult stem cells play mostly repair and tissue matrix secretion role. Among various adult stem cell types, mesenchymal stem cells play an important role to maintain tissue homeostasis. These cells are available in almost all the tissue types and exhibit features similar to the ESCs. These cells are immunoevasive, immune modulatory, and/anti-inflammatory, and bear properties of self-renewal (although limited), multiplication, and differentiation. In addition, these cells are able to migrate and home-in to the distant tissues. All these features make these cells potential candidates for therapeutic applications and drug development. There are various studies that have favored their role in therapeutics and drug development, although more studies and further insights are desired to make stem cell therapy a definitive therapeutic option.


2021 ◽  
Vol 22 (2) ◽  
pp. 666
Author(s):  
Toshio Takahashi

Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.


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