scholarly journals Analyzing Impetus of Regenerative Cellular Therapeutics in Myocardial Infarction

2020 ◽  
Vol 9 (5) ◽  
pp. 1277 ◽  
Author(s):  
Ming-Long Chang ◽  
Yu-Jui Chiu ◽  
Jian-Sing Li ◽  
Khoot-Peng Cheah ◽  
Hsiu-Hu Lin
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Cardiac Fibroblasts ◽  
Cell Lineage ◽  
Specific Cell ◽  
Paracrine Factors ◽  
Differentiation Potential ◽  
Cell Based Therapy ◽  
Organ Specific ◽  
Made In

Both vasculature and myocardium in the heart are excessively damaged following myocardial infarction (MI), hence therapeutic strategies for treating MI hearts should concurrently aim for true cardiac repair by introducing new cardiomyocytes to replace lost or injured ones. Of them, mesenchymal stem cells (MSCs) have long been considered a promising candidate for cell-based therapy due to their unspecialized, proliferative differentiation potential to specific cell lineage and, most importantly, their capacity of secreting beneficial paracrine factors which further promote neovascularization, angiogenesis, and cell survival. As a consequence, the differentiated MSCs could multiply and replace the damaged tissues to and turn into tissue- or organ-specific cells with specialized functions. These cells are also known to release potent anti-fibrotic factors including matrix metalloproteinases, which inhibit the proliferation of cardiac fibroblasts, thereby attenuating fibrosis. To achieve the highest possible therapeutic efficacy of stem cells, the other interventions, including hydrogels, electrical stimulations, or platelet-derived biomaterials, have been supplemented, which have resulted in a narrow to broad range of outcomes. Therefore, this article comprehensively analyzed the progress made in stem cells and combinatorial therapies to rescue infarcted myocardium.

Therapeutic Potential of Amniotic Fluid Derived Mesenchymal Stem Cells Based on their Differentiation Capacity and Immunomodulatory Properties

2019 ◽  
Vol 14 (4) ◽  
pp. 327-336 ◽  
Author(s):  
Carl R. Harrell ◽  
Marina Gazdic ◽  
Crissy Fellabaum ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Animal Models ◽  
Amniotic Fluid ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Therapeutic Effects ◽  
Differentiation Potential ◽  
Differentiation Capacity ◽  
Cell Based Therapy

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.

Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

2020 ◽  
Vol 15 (6) ◽  
pp. 531-546 ◽  
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Critical Role ◽  
The Self ◽  
Specific Cell ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

Mini Review; Differentiation of Human Pluripotent Stem Cells into Oocytes

2020 ◽  
Vol 15 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Gaifang Wang ◽  
Maryam Farzaneh
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cells ◽  
Human Oocyte ◽  
Differentiation Potential ◽  
Cell Lineages ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.

scholarly journals Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
HuiYa Li ◽  
DanQing Hu ◽  
Guilin Chen ◽  
DeDong Zheng ◽  
ShuMei Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Paracrine Factors ◽  
Dual Treatment

AbstractBoth weak survival ability of stem cells and hostile microenvironment are dual dilemma for cell therapy. Adropin, a bioactive substance, has been demonstrated to be cytoprotective. We therefore hypothesized that adropin may produce dual protective effects on the therapeutic potential of stem cells in myocardial infarction by employing an adropin-based dual treatment of promoting stem cell survival in vitro and modifying microenvironment in vivo. In the current study, adropin (25 ng/ml) in vitro reduced hydrogen peroxide-induced apoptosis in rat bone marrow mesenchymal stem cells (MSCs) and improved MSCs survival with increased phosphorylation of Akt and extracellular regulated protein kinases (ERK) l/2. Adropin-induced cytoprotection was blocked by the inhibitors of Akt and ERK1/2. The left main coronary artery of rats was ligated for 3 or 28 days to induce myocardial infarction. Bromodeoxyuridine (BrdU)-labeled MSCs, which were in vitro pretreated with adropin, were in vivo intramyocardially injected after ischemia, following an intravenous injection of 0.2 mg/kg adropin (dual treatment). Compared with MSCs transplantation alone, the dual treatment with adropin reported a higher level of interleukin-10, a lower level of tumor necrosis factor-α and interleukin-1β in plasma at day 3, and higher left ventricular ejection fraction and expression of paracrine factors at day 28, with less myocardial fibrosis and higher capillary density, and produced more surviving BrdU-positive cells at day 3 and 28. In conclusion, our data evidence that adropin-based dual treatment may enhance the therapeutic potential of MSCs to repair myocardium through paracrine mechanism via the pro-survival pathways.

scholarly journals Human Amniotic Fluid Mesenchymal Stem Cells from Second- and Third-Trimester Amniocentesis: Differentiation Potential, Molecular Signature, and Proteome Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Jurate Savickiene ◽  
Grazina Treigyte ◽  
Sandra Baronaite ◽  
Giedre Valiuliene ◽  
Algirdas Kaupinis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Amniotic Fluid ◽  
Expression Patterns ◽  
Specific Gene ◽  
Specific Cell ◽  
Third Trimester ◽  
Human Amniotic Fluid ◽  
Differentiation Potential

Human amniotic fluid stem cells have become an attractive stem cell source for potential applications in regenerative medicine and tissue engineering. The aim of this study was to characterize amniotic fluid-derived mesenchymal stem cells (AF-MSCs) from second- and third-trimester of gestation. Using two-stage protocol, MSCs were successfully cultured and exhibited typical stem cell morphological, specific cell surface, and pluripotency markers characteristics. AF-MSCs differentiated into adipocytes, osteocytes, chondrocytes, myocytes, and neuronal cells, as determined by morphological changes, cell staining, and RT-qPCR showing the tissue-specific gene presence for differentiated cell lineages. Using SYNAPT G2 High Definition Mass Spectrometry technique approach, we performed for the first time the comparative proteomic analysis between undifferentiated AF-MSCs from late trimester of gestation and differentiated into myogenic, adipogenic, osteogenic, and neurogenic lineages. The analysis of the functional and expression patterns of 250 high abundance proteins selected from more than 1400 demonstrated the similar proteome of cultured and differentiated AF-MSCs but the unique changes in their expression profile during cell differentiation that may help the identification of key markers in differentiated cells. Our results provide evidence that human amniotic fluid of second- and third-trimester contains stem cells with multilineage potential and may be attractive source for clinical applications.

Abstract 362: Proteomic Analysis of Low Oxygen Tension-Induced Secretome of Adipose Tissue-Derived Stem Cells

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Zeljko Bosnjak ◽  
Bassam Wakim ◽  
Yasheng Yan ◽  
Scott Canfield ◽  
Chika Kikuchi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Oxygen Tension ◽  
Proteomic Analysis ◽  
Stem Cell Markers ◽  
Paracrine Factors ◽  
Differentiation Potential ◽  
Trophic Effect ◽  
Lower Oxygen

Growing evidence from animal studies shows that adipose tissue-derived stem cells (ASCs) improve cardiac function of infarcted hearts. It is commonly accepted that therapeutic potential of ASCs may depend more on their paracrine effects than differentiation potential. The underlying mechanisms remain unclear. However, most data regarding paracrine factors were obtained from ASCs cultured in normoxic condition (20%). The present study investigated how in vivo physiological oxygen (4%) tension influenced the secretome of ASCs. ASCs were isolated from three 8-week-old BALB/c mice. ASCs were confirmed by the expression of stem cell markers (CD44 and CD90) and their capacity to differentiate into adipocytes and osteocytes. ASCs at passage 5 were cultured in normoxic (20%) and lower oxygen (4%) incubators and conditioned for 24 h (3 cultures/group). The conditioned media (CM) from ASCs were subjected to trypsin digestion followed by analysis using automated nano-flow liquid chromatography tandem mass spectrometry. The collected LC/MS/MS data were searched against the rodent subset of the Uniprot database and the total proteomes were identified. The data were from 6 technical replicates. A total of 28 proteins were identified and 7 proteins were unique to normoxic CM. Of the 21 common proteins detected in both normoxic and lower oxygen CM, 9 were extracellular matrix proteins. The abundance of 6 of these proteins (e.g., collagen I and laminin) differed noticeably between normoxic and lower oxygen CM. In addition, a greater amount of cytokine CXCL5 and matrix metalloproteinase (MMP)-2 was detected in lower oxygen CM than in normoxic CM while tissue inhibitor of metalloproteinase (TIMP)-1 was only detected in normoxic CM. These results indicate that lower oxygen tension differentially regulates the secretome of ASCs. Extrapolating the results of this study to the in vivo setting, it would appear that injected ASCs may exert their anti-fibrotic and trophic effect by 1) directly regulating the balance of MMP/TIMP production and preventing collagen accumulation in ischemic hearts to decrease fibrosis, and 2) secreting trophic factors including CXCL5. These data suggest that proteomic analysis of CM is useful for elucidation of the paracrine effect of ASCs in vivo.

Abstract 258: Pitx2 Promotes Murine Myocardial Regeneration after Myocardial Injury

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
GE TAO ◽  
Elzbieta Klysik ◽  
Yuka Morikawa ◽  
James F Martin
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Myocardial Injury ◽  
De Novo ◽  
The United States ◽  
Myocardial Regeneration ◽  
Mouse Heart ◽  
Specific Cell ◽  
Regulation Of Transcription ◽  
Regenerative Therapy

Myocardial infarction is the leading cause of morbidity and mortality in the United States. Compromised myocardial function, due to the lack of self-renewal capacity in mature hearts, is a major reason for heart failure. Available therapies can only ameliorate, but not reverse the loss of functional myocardium. With heart transplantation as the only available cure, design of an effective regenerative therapy has become imperative for cardiovascular research. To repopulate the heart with de novo cardiomyocytes, most attempts have been based on the transplantation of cardiac, non-cardiac stem cells or their derivatives, however a more profound knowledge of stem cells is required for achieving significant progress. Meanwhile, triggering endogenous regenerative capacity is a compelling strategy for cardiac repair. It has been reported that proliferation of pre-existing cardiomyocytes strongly contributes to regeneration. Thus, efforts have been made to reintroduce mature cardiomyocytes into mitotic cycle. The mechanisms underlying the proliferation of cardiomyocytes during development and their homeostasis during adulthood are not fully understood, but likely require tight regulation of transcription factors in specific cell types. We have previously shown that the mouse Hippo kinase cascade is a major heart-size control pathway during development. In addition, activation of Yap, a transcriptional cofactor inhibited by Hippo, by genetically disrupting Hippo signaling is sufficient to induce juvenile and adult myocardial regeneration after surgery-induced myocardial infarction. Here we identified the paired-like homeodomain transcription factor 2 (pitx2) as a potential downstream target and cofactor of Yap in mouse heart. Our data indicates that Pitx2 expression is induced by myocardial injury, and is required for neonatal myocardial regeneration in a postnatal day 1 (P1) apex resection model. Further studies show that over-expression of pitx2 in adult cardiomyocytes is sufficient to promote the restoration of myocardial structure and function after myocardial infarction. Together, we show that pitx2 is a new manipulator of myocardial regeneration and could serve as a novel therapeutic target in cardiac regenerative therapy.

scholarly journals Polymeric sheet actuators with programmable bioinstructivity

2020 ◽  
Vol 117 (4) ◽  
pp. 1895-1901 ◽  
Author(s):  
Zijun Deng ◽  
Weiwei Wang ◽  
Xun Xu ◽  
Oliver E. C. Gould ◽  
Karl Kratz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Shape Change ◽  
Cell Lineage ◽  
Fundamental Principle ◽  
Signaling Cascades ◽  
Specific Cell ◽  
Polymer Actuator ◽  
Intracellular Ca ◽  
Functional Biomaterials ◽  
Biochemical Signals

Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSCs). Using a grid on its underside, the shape change of polymer sheet, as well as cell morphology, calcium (Ca2+) influx, and focal adhesion assembly, could be visualized and quantified. This paper gives compelling evidence that the temperature sensing and mechanosensing of MSCs are interconnected via intracellular Ca2+. Up-regulated Ca2+ levels lead to a remarkable alteration of histone H3K9 acetylation and activation of osteogenic related genes. The interplay of physical, thermal, and biochemical signaling was utilized to accelerate the cell differentiation toward osteogenic lineage. The approach of programmable bioinstructivity provides a fundamental principle for functional biomaterials exhibiting multifaceted stimuli on differentiation programs. Technological impact is expected in the tissue engineering of periosteum for treating bone defects.

Skeletal Muscle-Derived Stem Cells: Implications for Cell-Mediated Therapies

Medicina ◽  
2011 ◽  
Vol 47 (9) ◽  
pp. 469 ◽  
Author(s):  
Arvydas Ūsas ◽  
Justinas Mačiulaitis ◽  
Romaldas Mačiulaitis ◽  
Neli Jakubonienė ◽  
Arvydas Milašius ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Trophic Factors ◽  
Acute Injury ◽  
Cartilage Defects ◽  
Specific Cell ◽  
Muscle Injuries ◽  
Differentiation Potential ◽  
Isolation And Characterization ◽  
Myogenic Stem Cells

Current advances in stem cell research and innovative biological approaches in the field of tissue engineering and regenerative medicine could eventually translate into prospective clinical applications. Various adult organs and tissues harbor stem and progenitor cells that could potentially be used to repair, regenerate, and restore a variety of different tissues following acute injury or tissue destructive diseases. Skeletal muscle is a very convenient and plentiful source of somatic stem cells. It contains several distinct populations of myogenic stem cells including satellite cells that are mainly responsible for muscle growth and regeneration, and multipotent muscle-derived stem cells (MDSCs). Although both cell populations share some phenotypic similarities, MDSCs display a much greater differentiation potential in vitro and are capable of regenerating various tissues in vivo. Furthermore, these cells not only participate in the regeneration process by differentiating into tissue-specific cell types, but also promote endogenous tissue repair by secreting a multitude of trophic factors. In this article, we describe the biological aspects of MDSC isolation and characterization and provide an overview of potential therapeutic application of these cells for the treatment of cardiac and skeletal muscle injuries and diseases, urological dysfunction, and bone and cartilage defects. We also discuss major challenges and limitations currently faced by MDSC-based therapies that await resolution before these techniques can be applied clinically.

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