Transplantation of neuronal cells induced from human mesenchymal stem cells improves neurological functions after stroke without cell fusion

2010 ◽  
Vol 88 (16) ◽  
pp. 3598-3609 ◽  
Author(s):  
Haiyan Xu ◽  
Kazunori Miki ◽  
Satoru Ishibashi ◽  
Jun Inoue ◽  
Liyuan Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Fusion ◽  
Neuronal Cells ◽  
Human Mesenchymal Stem Cells

scholarly journals Characterization of Human Mesenchymal Stem Cells from Different Tissues and Their Membrane Encasement for Prospective Transplantation Therapies

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Eva Schmelzer ◽  
Daniel T. McKeel ◽  
Jörg C. Gerlach
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Cell Fusion ◽  
Human Mesenchymal Stem Cells ◽  
Surface Markers ◽  
Multilineage Differentiation ◽  
Differentiation Potential ◽  
Donor Cells ◽  
Different Tissues

Human mesenchymal stem cells can be isolated from various organs and are in studies on therapeutic cell transplantation. Positive clinical outcomes of transplantations have been attributed to both the secretion of cytokines and growth factors as well as the fusion of donor cells with that of the host. We compared human mesenchymal stem cells from six different tissues for their transplantation-relevant potential. Furthermore, for prospective allogenic transplantation we developed a semipermeable hollow-fiber membrane enclosure, which would prevent cell fusion, would provide an immune barrier, and would allow for easy removal of donor cells from patients after recovery. We investigated human mesenchymal stem cells from adipose tissue, amniotic tissue, bone marrow, chorionic tissue, liver, and umbilical cord. We compared their multilineage differentiation potential, secretion of growth factors, and the expression of genes and surface markers. We found that although the expression of typical mesenchymal stem cell-associated gene THY1 and surface markers CD90 and CD73 were mostly similar between mesenchymal stem cells from different donor sites, their expression of lineage-specific genes, secretion of growth factors, multilineage differentiation potential, and other surface markers were considerably different. The encasement of mesenchymal stem cells in fibers affected the various mesenchymal stem cells differently depending on their donor site. Conclusively, mesenchymal stem cells isolated from different tissues were not equal, which should be taken into consideration when deciding for optimal sourcing for therapeutic transplantation. The encasement of mesenchymal stem cells into semipermeable membranes could provide a physical immune barrier, preventing cell fusion.

scholarly journals Evaluation of Priming Efficiency of Forskolin in Tissue-Specific Human Mesenchymal Stem Cells into Dopaminergic Neurons: An In Vitro Comparative Study

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2058
Author(s):  
Manisha Singh ◽  
Pardeep Kumar Vaishnav ◽  
Amit Kumar Dinda ◽  
Sujata Mohanty
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Calcium Ion ◽  
Dopaminergic Neurons ◽  
Neuronal Cells ◽  
Human Mesenchymal Stem Cells ◽  
Generate Functional ◽  
Efficient Manner ◽  
Protein Levels

Background: Human mesenchymal stem cells (hMSC) can be derived from various tissue sources and differentiated into dopaminergic (DAergic) neurons using various types of inducers. There are several strategies that have been reported to generate functional dopaminergic neuronal cells from hMSCs in the most efficient manner possible. However, this area is still under extensive research. In this study, we aim to compare hMSCs derived from bone marrow (BM), adipose tissue (AD) and dental pulp (DP) to generate functional dopaminergic neurons, using FGF2 and forskolin. Post-differentiation, multiple factors were used to characterize the cells at morphological, morphometric, ultra-structural, mRNA and protein levels for various markers (Nestin, NF, MAP2, Tuj1, TH, DAT, PitX3, Ngn2, Kv4.2, SCN5A). Cells’ functionality was studied by calcium ion imaging, along with the amount of dopamine secreted by the cells in the culture medium. Results: Data analysis revealed that forskolin has comparable effect on BM- and AD-derived MSC (28.43% and 29.46% DAergic neurons, respectively), whereas DP-MSC (42.78 ± 1.248% DAergic neurons) show better outcome in terms of efficient generation of DAergic neuronal cells, expression of neuronal associated markers, dopamine release and calcium ion efflux. Ultra-structural studies by SEM and TEM also revealed a substantial change in both cellular morphology and composition of cellular organelles. It was observed that AD-MSCs showed the best neuronal features, at morphological, gene, and protein levels upon induction with the above-mentioned induction cocktail. Conclusion: It may be concluded that a combination of FGF2 and forskolin yields functionally active dopaminergic neuronal cells in vitro, with highest percentage of the same from AD-MSCs, as compared to that in BM-MSCs and DP-MSCs. The outcomes and comparative evaluation provide a substantial platform for further studies on molecular pathways involved in the process of DAergic neurogenesis in individual cases.

Human Mesenchymal Stem Cells Differentiate Promptly into Tissue-Specific Cell Types without Cell Fusion, Mitochondrial or Membrane Vesicular Transfer in Fetal Sheep.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 436-436 ◽  
Author(s):  
Evan J. Colletti ◽  
Judith A. Airey ◽  
Esmail D. Zanjani ◽  
Christopher D. Porada ◽  
Graça Almeida-Porada
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Fusion ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Type I ◽  
Fetal Sheep ◽  
Tissue Specific ◽  
The Brain

Abstract Despite the exciting reports regarding the ability of human mesenchymal stem cells (MSC) to differentiate into different cells of different organs, the mechanism by which this process occurs remains controversial. Several possible explanations have been put forth as an alternative to the existence of a true differentiation mechanism. We previously showed that MSC, at a single cell level, are able to differentiate into cells of different germ cell layers. In the present study, we investigated whether transfer of mitochondria or membrane-derived vesicles between cells and/or cell fusion participate in the events that lead to the change of phenotype of MSC upon transplantation (Tx). To this end, 54 sheep fetuses (55–60 gestational days) were Tx intra-peritoneally with Stro-1+,CD45−, Gly-A- MSC labeled prior to Tx with either CFSE, that irreversibly couples to both intracellular and cell-surface proteins, or DiD that efficiently labels all cell membranes and intracellular organelles, such as mitochondria. Evaluation of the recipients’ different organs started at 20h post-Tx and continued at 25,30,40,60 and 120h. MSC reached the liver at 25h post-Tx (0.033%±0.0) with maximal engraftment at 40h (0.13%±0.02). MSC were first detected in the lung (0.028%±0.0) and brain (0.034%±0.0) at 30h and 40h respectively. In the brain, engraftment peaked at 60 hours post-Tx (0.08%±0.0) and in the lung at 120h (0.09%±0.01). Normalization of the number of engrafted cells per tissue mass and number of Tx cells revealed that 26% of the Tx MSC reached the lung; 2% the liver; and 3% the brain. Since the decreasing number of CFSE+ and DiD+ cells detected after 120h could be due to cell division, Ki67 staining was performed and revealed that 85–95% of the engrafted cells proliferated upon lodging in the organs, and divided throughout the evaluation period. To determine MSC differentiative timeline, confocal microscopy was performed to assess whether CFSE+ or DiD+ cells expressed tissue-specific markers (MSC were negative for these markers prior to transplant) within the engrafted organs. In the liver at 25h post-Tx, all CFSE+ or DiD+ cells co-expressed alpha-fetoprotein, demonstrating the rapid switch from an MSC to a fetal hepatocyte-like phenotype. In the lung, co-localization of pro-surfactant protein and CFSE/DiD was first detected at 30h post-Tx, but cells remained negative for Caveolin1; a phenotype that is consistent with differentiation to a type II epithelial cell, but not to a more mature type I. In the brain, MSC expressed Tau promptly, but synaptophysin expression was not detected until 120h. In situ hybridization on serial sections using either a human- or sheep-specific probe, with simultaneous visualization of CFSE+ or DiD+ cells allowed us to show that no membrane or mitochondrial transfer had occurred, since none of the sheep cells contained CFSE or DiD, and all of the dye+ cells hybridized only to the human probe. Furthermore, this combined methodology enabled us to determine that differentiation to all of the different cell types had occurred in the absence of cell fusion. In conclusion, MSC engraft multiple tissues rapidly, undergo proliferation, and give rise to tissue-specific cell types in the absence of cellular fusion or the transfer of mitochondria or membrane vesicles.

scholarly journals Human mesenchymal stem cells ectopically expressing full-length dystrophin can complement Duchenne muscular dystrophy myotubes by cell fusion

2005 ◽  
Vol 15 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Manuel A.F.V. Gonçalves ◽  
Antoine A.F. de Vries ◽  
Maarten Holkers ◽  
Marloes J.M. van de Watering ◽  
Ietje van der Velde ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Cell Fusion ◽  
Human Mesenchymal Stem Cells ◽  
Full Length

Neurogenesis Is Induced by Electrical Stimulation of Human Mesenchymal Stem Cells Co-Cultured With Mature Neuronal Cells

2015 ◽  
Vol 15 (11) ◽  
pp. 1586-1594 ◽  
Author(s):  
Sang Jun Park ◽  
Ji Sun Park ◽  
Han Na Yang ◽  
Se Won Yi ◽  
Chun-Ho Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Electrical Stimulation ◽  
Neuronal Cells ◽  
Human Mesenchymal Stem Cells ◽  
Stimulation Of

scholarly journals Human Mesenchymal Stem Cells Reprogram Adult Cardiomyocytes Toward a Progenitor-Like State Through Partial Cell Fusion and Mitochondria Transfer

Stem Cells ◽  
2011 ◽  
Vol 29 (5) ◽  
pp. 812-824 ◽  
Author(s):  
Adrien Acquistapace ◽  
Thierry Bru ◽  
Pierre-François Lesault ◽  
Florence Figeac ◽  
Amélie E. Coudert ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Fusion ◽  
Human Mesenchymal Stem Cells ◽  
Adult Cardiomyocytes ◽  
Mitochondria Transfer
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