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.

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.

From mesenchymal stem cells and stromal cells - from bench to bedside

2019 ◽  
Vol 1 (1) ◽  
pp. 36-39
Author(s):  
Bernd Giebel ◽  
Verena Börger ◽  
Mario Gimona ◽  
Eva Rohde
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stromal Cells ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Cell Replacement ◽  
Beneficial Effects ◽  
Promising Tool

Human mesenchymal stem/stromal cells (MSCs) represent a promising tool in regenerative medicine. Until now, almost one thousand NIH-registered clinical trials investigated their immunomodulatory and pro-regenerative therapeutic potential in various diseases. Despite controversial reports regarding the efficacy of MSC-treatments, MSCs appear to exert their beneficial effects in a paracrine manner rather than by cell replacement. In this context, extracellular vesicles (EVs), such as exosomes and microvesicles, seem to induce the MSCs’ therapeutic effects. Here, we briefly illustrate the potential of MSC-EVs as therapeutic agent of the future.

scholarly journals Effects of Severe Hypoxia on Bone Marrow Mesenchymal Stem Cells Differentiation Potential

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Claudia Cicione ◽  
Emma Muiños-López ◽  
Tamara Hermida-Gómez ◽  
Isaac Fuentes-Boquete ◽  
Silvia Díaz-Prado ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Molecular Mechanisms ◽  
Control Point ◽  
Severe Hypoxia ◽  
Marker Genes ◽  
Differentiation Potential ◽  
Differentiation Capacity ◽  
Hypoxic Conditions

Background. The interests in mesenchymal stem cells (MSCs) and their application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently hypoxia has been indicated as crucial for complete chondrogenesis. We aimed at analyzing bone marrow MSCs (BM-MSCs) differentiation capacity under normoxic and severe hypoxic culture conditions.Methods. MSCs were characterized by flow cytometry and differentiated towards adipocytes, osteoblasts, and chondrocytes under normoxic or severe hypoxic conditions. The differentiations were confirmed comparing each treated point with a control point made of cells grown in DMEM and fetal bovine serum (FBS).Results. BM-MSCs from the donors displayed only few phenotypical differences in surface antigens expressions. Analyzing marker genes expression levels of the treated cells compared to their control point for each lineage showed a good differentiation in normoxic conditions and the absence of this differentiation capacity in severe hypoxic cultures.Conclusions. In our experimental conditions, severe hypoxia affects thein vitrodifferentiation potential of BM-MSCs. Adipogenic, osteogenic, and chondrogenic differentiations are absent in severe hypoxic conditions. Our work underlines that severe hypoxia slows cell differentiation by means of molecular mechanisms since a decrease in the expression of adipocyte-, osteoblast-, and chondrocyte-specific genes was observed.

scholarly journals Modulation of Adult Mesenchymal Stem Cells Activity by Toll-Like Receptors: Implications on Therapeutic Potential

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Olga DelaRosa ◽  
Eleuterio Lombardo
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Culture Conditions ◽  
Toll Like Receptors ◽  
Adult Mesenchymal Stem Cells ◽  
Special Relevance ◽  
Tlr Signalling

Mesenchymal stem cells (MSCs) are of special interest as therapeutic agents in the settings of both chronic inflammatory and autoimmune diseases. Toll-like receptors (TLR) ligands have been linked with the perpetuation of inflammation in a number of chronic inflammatory diseases due to the permanent exposure of the immune system to TLR-specific stimuli. Therefore, MSCs employed in therapy can be potentially exposed to TLR ligands, which may modulate MSC therapeutic potential in vivo. Recent results demonstrate that MSCs are activated by TLR ligands leading to modulation of the differentiation, migration, proliferation, survival, and immunosuppression capacities. However inconsistent results among authors have been reported suggesting that the source of MSCs, TLR stimuli employed or culture conditions play a role. Notably, activation by TLR ligands has not been reported to modulate the “immunoprivileged” phenotype of MSCs which is of special relevance regarding the use of allogeneic MSC-based therapies. In this review, we discuss the available data on the modulation of MSCs activity through TLR signalling.

Bone Marrow Mesenchymal Stem Cells Exhibit a Transdifferentiation and Therapeutic Effects in a Murine Model of Orthotopic Hepatocellular Carcinoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5133-5133
Author(s):  
Jun Ren ◽  
Hanfang Jiang ◽  
Lijun Di ◽  
Guohong Song
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Murine Model ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Tumor Diameter ◽  
Hepatic Differentiation ◽  
Marrow Mesenchymal Stem Cells

Abstract Background and Aim: Bone marrow stem cells can differentiate into mature hepatocytes in vitro and in vivo. Moreover, recent study shown bone marrow mesenchymal stem cells (MSCs) are the most potent component in hepatic differentiation, suggesting that the transplantation of MSCs is a promising treatment for liver disease. However, little information is available about the therapeutic potential of MSCs transplantation in cases of hepatic cell carcinoma (HCC). Here, we transplanted bone marrow-derived MSCs to testify their effects in a murine model of orthotopic HCC. Methods:MSCs were obtained from tow male strains of β-galactosidase (β-gal) transgenic mouse(Rosa 26) and BALB/c mouse. MSCs were injected into tumor in BALB/c femal murine models of orthotopic HCC. Tumor growths were assessed by MRI on 7 days and survival rates were observed. When mouse was dying, the liver was removed from each treated mouse and evaluated by x-gal staining, and immunohistochemisty as well. Results: MSCs transplantation increased the survival of hepatocellular carcinoma-bearing mice(25.5±4.5days verus 21.3±1.7days, p=0.025) and decreased tumor diameter slightly (7.7±2.9mm versus 9.4±2.8mm, p=0.284). MSCs transplanted directly into the tumor and/ or normal hepatic parenchyma in the same liver lobe localized mainly at the border between the tumor cells and normal liver parenchyma, induced a large area of coagulative necrosis in the tumor bed. Some engrafted MSCs were positive for albumin. There are in the carcinoma bearing BALB/c mice with MSCs implanted, whether MSCs from BALB/c mice or from Rosa 26 transgenic mice. Conclusion: Our results suggest that the therapeutical effects of MSCs might be mediated not only by their differentiation into hepatocyte, but also mainly by they possess intrinsic antineoplastic properties.

scholarly journals From Blood to the Brain: Can Systemically Transplanted Mesenchymal Stem Cells Cross the Blood-Brain Barrier?

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Linan Liu ◽  
Mark A. Eckert ◽  
Hamidreza Riazifar ◽  
Dong-Ku Kang ◽  
Dritan Agalliu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Inflammatory Diseases ◽  
Neurological Diseases ◽  
Brain Barrier ◽  
Therapeutic Effects ◽  
Blood Brain ◽  
The Brain

Systemically infused mesenchymal stem cells (MSCs) are emerging therapeutics for treating stroke, acute injuries, and inflammatory diseases of the central nervous system (CNS), as well as brain tumors due to their regenerative capacity and ability to secrete trophic, immune modulatory, or other engineered therapeutic factors. It is hypothesized that transplanted MSCs home to and engraft at ischemic and injured sites in the brain in order to exert their therapeutic effects. However, whether MSCs possess the ability to migrate across the blood-brain barrier (BBB) that separates the blood from the brain remains unresolved. This review analyzes recent advances in this area in an attempt to elucidate whether systemically infused MSCs are able to actively transmigrate across the CNS endothelium, particularly under conditions of injury or stroke. Understanding the fate of transplanted MSCs and their CNS trafficking mechanisms will facilitate the development of more effective stem-cell-based therapeutics and drug delivery systems to treat neurological diseases and brain tumors.

Osteoblastic differentiation potential of human amniotic fluid-derived mesenchymal stem cells in different culture conditions

2018 ◽  
Vol 120 (8) ◽  
pp. 701-712 ◽  
Author(s):  
Tanongsak Laowanitwattana ◽  
Sirinda Aungsuchawan ◽  
Suteera Narakornsak ◽  
Runchana Markmee ◽  
Waleephan Tancharoen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Amniotic Fluid ◽  
Osteoblastic Differentiation ◽  
Culture Conditions ◽  
Human Amniotic Fluid ◽  
Differentiation Potential

scholarly journals Mesenchymal Stem Cells for Cartilage Regeneration of TMJ Osteoarthritis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Dixin Cui ◽  
Hongyu Li ◽  
Xin Xu ◽  
Ling Ye ◽  
Xuedong Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cartilage Regeneration ◽  
Cartilage Degeneration ◽  
Self Healing ◽  
Condylar Cartilage ◽  
Differentiation Potential ◽  
Tissue Repair And Regeneration ◽  
Cell Based Therapy ◽  
Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, characterized by progressive cartilage degradation, subchondral bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical treatments have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In recent years, stem cell-based therapy has raised much attention as an alternative approach towards tissue repair and regeneration. Mesenchymal stem cells (MSCs), derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ OA. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the trophic modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will briefly discuss the pathogenesis of cartilage degeneration in TMJ OA and emphasize the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ OA, particularly focusing on the MSC-based therapy and tissue engineering.

scholarly journals Cell-Based Therapy for Stroke

Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2854-2862 ◽  
Author(s):  
You Jeong Park ◽  
Kuniyasu Niizuma ◽  
Maxim Mokin ◽  
Mari Dezawa ◽  
Cesar V. Borlongan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Therapeutic Potential ◽  
Host Tissue ◽  
In Vivo Models ◽  
Cell Based Therapy ◽  
Muse Cells

Stem cell-based regenerative therapies may rescue the central nervous system following ischemic stroke. Mesenchymal stem cells exhibit promising regenerative capacity in in vitro studies but display little to no incorporation in host tissue after transplantation in in vivo models of stroke. Despite these limitations, clinical trials using mesenchymal stem cells have produced some functional benefits ascribed to their ability to modulate the host’s inflammatory response coupled with their robust safety profile. Regeneration of ischemic brain tissue using stem cells, however, remains elusive in humans. Multilineage-differentiating stress-enduring (Muse) cells are a distinct subset of mesenchymal stem cells found sporadically in connective tissue of nearly every organ. Since their discovery in 2010, these endogenous reparative stem cells have been investigated for their therapeutic potential against a variety of diseases, including acute myocardial infarction, stroke, chronic kidney disease, and liver disease. Preclinical studies have exemplified Muse cells’ unique ability mobilize, differentiate, and engraft into damaged host tissue. Intravenously transplanted Muse cells in mouse lacunar stroke models afforded functional recovery and long-term engraftment into the host neural network. This mini-review article highlights these biological properties that make Muse cells an exceptional candidate donor source for cell therapy in ischemic stroke. Elucidating the mechanism behind the therapeutic potential of Muse cells will undoubtedly help optimize stem cell therapy for stroke and advance the field of regenerative medicine.

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