Analysis of Key Distinct Biological Characteristics of Human Placenta-Derived Mesenchymal Stromal Cells and Individual Heterogeneity Attributing to Donors

2021 ◽  
pp. 1-13
Author(s):  
Chenxu Tai ◽  
Liudi Wang ◽  
Yuanyuan Xie ◽  
Tianyun Gao ◽  
Feifei Huang ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Human Placenta ◽  
Immune Regulation ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Adipogenic Differentiation ◽  
Individual Heterogeneity ◽  
Differentiation Potential ◽  
Different Origin

For potential clinical applications in the future, we investigated the distinct biological features of mesenchymal stromal cells (MSCs) derived from different origin areas of human placenta and individual heterogeneity among different donors. Chorionic plate MSCs (CP-MSCs), amniotic membrane MSCs (AM-MSCs), and decidual plate MSCs (DP-MSCs) were isolated from 5 human placentae and were analyzed in terms of main features of MSCs including surface marker profile, growth, differentiation potential, immune regulation capability, and tubulin acetylation (Ac-tubulin). The expression profile of surface markers in the 3 types of MSCs derived from the 5 donors was relatively stable. Heterogeneity was found in growth, differentiation potential, and immune regulation among MSCs according to the different areas of isolation and different donors. CP-MSCs and AM-MSCs derived from the placentae of donors 1–3 had a higher osteogenic differentiation potential than the corresponding DP-MSCs, but those derived from the placentae of donors 4 and 5 had a markedly lower osteogenic differentiation potential than DP-MSCs. All CP-MSCs derived from donors 1–3 had the highest adipogenic differentiation potential, but CP-MSCs derived from donors 4 and 5 did not show strong capability of adipogenic differentiation. CP-MSCs markedly inhibited the proliferation of peripheral blood mononuclear cells (PBMCs) induced by phytohemagglutinin, whereas AM- and DP-MSCs did not. All MSCs decreased the proportion of CD3+/CD8–/IFN-γ+ Th1 and CD3+/CD8–/IL17+ Th17 cells, but increased the proportion of Treg cells in PBMCs, with individual differences among the 5 donors. DP-MSCs from donors 1 and 2 had higher levels of Ac-tubulin compared with CP- and AM-MSCs. However, the levels of Ac-tubulin in AM-MSCs from donors 3 and 5 were higher than those of the other 2 types of MSCs. Our results revealed that there was tissue-specific heterogeneity among the 3 types of MSCs from different origin tissues of placenta and individual heterogeneity among donors. In future, the pre-selected placenta-derived MSCs with specific biological advantages may improve the curative effect of cell therapy in different situations.

Human Placenta-Derived CD146-Positive Mesenchymal Stromal Cells Display a Distinct Osteogenic Differentiation Potential

2015 ◽  
Vol 24 (13) ◽  
pp. 1558-1569 ◽  
Author(s):  
Christine Ulrich ◽  
Tanja Abruzzese ◽  
Jan K. Maerz ◽  
Manuel Ruh ◽  
Bastian Amend ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Human Placenta ◽  
Stromal Cells ◽  
Differentiation Potential

scholarly journals Individual heterogeneity screened umbilical cord-derived mesenchymal stromal cells with high Treg promotion demonstrate improved recovery of mouse liver fibrosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuanyuan Xie ◽  
Shuo Liu ◽  
Liudi Wang ◽  
Hui Yang ◽  
Chenxu Tai ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Growth Curve ◽  
Immune Regulation ◽  
Stromal Cells ◽  
Mouse Liver ◽  
Individual Heterogeneity ◽  
Therapeutic Outcomes ◽  
Multiple Donors

Abstract Background To investigate the heterogeneities of human umbilical cord mesenchymal stromal cells (HUCMSCs) derived from different donors and their therapeutic variations when applied to mouse liver fibrosis model. Methods The characteristics of HUCMSCs derived from multiple donors were comprehensively analyzed including expressions of surface markers, viability, growth curve, karyotype analysis, tumorigenicity, differentiation potentials, and immune regulation capability. Then, the HUCMSCs with distinct immunomodulatory effects were applied to treat mouse liver fibrosis and their therapeutic effects were observed. Results The HUCMSCs derived from multiple donors kept a high consistency in surface marker expressions, viability, growth curve, and tumorigenicity in nude mice but had robust heterogeneities in differentiation potentials and immune regulations. In addition, three HUCMSC lines applied to mice liver fibrosis model had different therapeutic outcomes, in line with individual immune regulation capability. Conclusion The HUCMSCs derived from different donors have individual heterogeneity, which potentially lead to distinct therapeutic outcomes in mouse liver fibrosis, indicating we could make use of the donor-variation of MSCs to screen out guaranteed general indicators of MSCs for specific diseases in further stromal cell therapy.

Lenalidomide Modulates the Phenotype and Function of Human Mesenchymal Stromal Cells From Healthy Donors and MDS Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3816-3816
Author(s):  
Manja Wobus ◽  
Gwendolin Dünnebier ◽  
Silvia Feldmann ◽  
Gerhard Ehninger ◽  
Martin Bornhauser ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Osteogenic Differentiation ◽  
Clinical Efficacy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Morphological Changes ◽  
Adipogenic Differentiation ◽  
Healthy Controls ◽  
Healthy Donors

Abstract Abstract 3816 Poster Board III-752 Introduction Recent studies in patients with MDS have clearly demonstrated the clinical efficacy of lenalidomide. However, its exact mechanisms of action have not been elucidated yet. Myelosuppression is the most common adverse event and seems to be dependent on dose as well MDS subtype, being rather infrequent in patients other than del5q. The aim of this study was to investigate whether lenalidomide affects the bone marrow microenvironment. Therefore, we analyzed in-vitro characteristics of isolated mesenchymal stromal cells (MSCs) from MDS patients and from healthy controls. Methods Bone marrow samples were collected from healthy donors (n=5) and patients with MDS (del5q MDS n=3, RA n=2, RAEB1/2 n=3). MSCs were isolated according to the standard adhesion protocol and cultured in the presence or absence of lenalidomide. Results Lenalidomide treatment of MSCs caused no morphological changes but proliferation was slightly increased. Typical surface molecules as CD73, CD90, CD105 and CD166 were expressed in MSCs from MDS patients at comparable levels to healthy controls. Lenalidomide treatment caused an upregulation of CD29 by 17.8 ± 4.4% and of CD73 by 24 ± 5.7% (mean fluorescence intensity). Investigating the cytokine production, we found lower IL-8 mRNA and protein levels in MSCs from MDS patients (mean in MDS MSC: 138.1 pg/ml vs. mean in healthy MSC: 1177 pg/ml). Interestingly, the IL-8 production can be increased by approximately 40% under lenalidomide treatment. MDS MSCs retained the capacity for adipogenic and osteogenic differentiation as well as their supportive function towards hematopoietic cells in long term culture-initiating assays (LTC-IC). However, the LTC-IC frequency was lower on MSC which had been preincubated with lenalidomide compared to controls. Lenalidomide also slightly accelerated osteogenic differentiation because mineralization started as early as on day 5 with lenalidomide whereas in the control cells first calcium deposits were visible after 7 days. Other samples showed augmented lipid vacuoles after adipogenic differentiation under lenalidomide treatment. Conclusion In conclusion, lenalidomide modulates the phenotype of MSC and leads to an increase of their IL-8 secretion by a yet unknown mechanism. Whether these in-vitro effects are associated with the clinical efficacy of this compound in patients with MDS remains to be investigated. Disclosures: Platzbecker: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Vertebral Bone Marrow-Derived Mesenchymal Stromal Cells from Osteoporotic and Healthy Patients Possess Similar Differentiation Properties In Vitro

2020 ◽  
Vol 21 (21) ◽  
pp. 8309
Author(s):  
El-Mustapha Haddouti ◽  
Thomas M. Randau ◽  
Cäcilia Hilgers ◽  
Werner Masson ◽  
Robert Pflugmacher ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Vertebral Body ◽  
Stromal Cells ◽  
Osteogenic Potential ◽  
Ion Release ◽  
Differentiation Potential ◽  
Phosphate Ion ◽  
Alp Activity ◽  
Immunomodulatory Capacity

Osteoporosis is a disease characterized by low bone mass and an increased risk of fractures. Although several cellular players leading to osteoporosis have been identified, the role of mesenchymal stromal cells (MSC) is still not fully elaborated. The aim of this study was, therefore, to isolate and characterize MSCs from vertebral body of healthy non-osteoporotic and osteoporotic patients, with a particular focus on their osteogenic differentiation potential. Isolated MSCs were characterized by their osteogenic, adipogenic, and chondrogenic differentiation, as well as surface marker expression, proliferation behavior, and immunomodulatory capacity. The mineralization process was confirmed using Alizarin Red S and alkaline phosphatase (ALP) stains and further evaluated by determining ALP activity, mineral deposition, and free phosphate ion release. MSCs from both healthy and osteoporotic patients showed common fibroblast-like morphology and similar proliferation behavior. They expressed the typical MSC surface markers and possessed immunomodulatory capacity. Both groups demonstrated solid trilineage differentiation potential; osteogenic differentiation was further confirmed by increased ALP activity, deposition of inorganic crystals, phosphate ion release, and expression of osteoblast marker genes. Overall, MSCs from osteoporotic and non-osteoporotic patients showed neither a difference in general MSC features nor in the detailed analysis regarding osteogenic differentiation. These data suggest that vertebral body MSCs from osteoporotic patients were not impaired; rather, they possessed full osteogenic potential compared to MSCs from non-osteoporotic patients.

scholarly journals Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mesude Bicer ◽  
Graeme S. Cottrell ◽  
Darius Widera
Keyword(s):  
Stem Cells ◽  
Cell Culture ◽  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Treatment Options ◽  
3D Cell Culture ◽  
Bone Diseases ◽  
Differentiation Potential ◽  
Number Of Patients

AbstractAs populations age across the world, osteoporosis and osteoporosis-related fractures are becoming the most prevalent degenerative bone diseases. More than 75 million patients suffer from osteoporosis in the USA, the EU and Japan. Furthermore, it is anticipated that the number of patients affected by osteoporosis will increase by a third by 2050. Although conventional therapies including bisphosphonates, calcitonin and oestrogen-like drugs can be used to treat degenerative diseases of the bone, they are often associated with serious side effects including the development of oesophageal cancer, ocular inflammation, severe musculoskeletal pain and osteonecrosis of the jaw.The use of autologous mesenchymal stromal cells/mesenchymal stem cells (MSCs) is a possible alternative therapeutic approach to tackle osteoporosis while overcoming the limitations of traditional treatment options. However, osteoporosis can cause a decrease in the numbers of MSCs, induce their senescence and lower their osteogenic differentiation potential.Three-dimensional (3D) cell culture is an emerging technology that allows a more physiological expansion and differentiation of stem cells compared to cultivation on conventional flat systems.This review will discuss current understanding of the effects of different 3D cell culture systems on proliferation, viability and osteogenic differentiation, as well as on the immunomodulatory and anti-inflammatory potential of MSCs.

scholarly journals Effects of Extreme High Temperatures on Proliferation, Cell Cycle, Cell Differentiation and ROS of Adipose-Derived Mesenchymal Stromal Cells

2021 ◽  
Author(s):  
Yuanhui Gao ◽  
Hui Cao ◽  
Shunlan Wang ◽  
Linlin Zheng ◽  
Haowei He ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
High Temperature ◽  
Cell Differentiation ◽  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Adipogenic Differentiation ◽  
Mitochondrial Activity ◽  
Growth Activity

Abstract Backgrounds: Global warming has led to extreme temperatures in different latitudinal regions, resulting in the extinction of a large number of species. This study focuses on the effects of extreme high temperatures on cell proliferation, cell cycle, cell differentiation and mitochondria activity in human adipose-derived mesenchymal stromal cells (hADSCs). Methods: hADSCs were divided into three groups and incubated in 37°C, 39°C and 40°C environment for 5 hours of exposure each day, and then to 37°C circumstances for further incubation. Cell surface markers, cell cycle, cell proliferation activity, mitochondrial activity and cell polarization were detected and analyzed by flow cytometry, CCK-8 assay, ROS and JC-1 staining respectively on the 1 st and 3 rd day of cell culture; osteogenic and adipogenic differentiation ability of hASCs was analyzed by staining after 21 days of osteogenic and adipogenic differentiation induction culture. Results The results of this study showed that hASCs grown under high temperature conditions had restricted growth activity, blocked S and G2 phases of the cell cycle, reduced cytokinesis and impaired mitochondrial activity, while their osteogenic differentiation ability and membrane potential depolarization were enhanced. Conclusions: hADSCs were subjected to high temperature stimulation with restricted growth activity, reduced cell division, impaired mitochondrial activity, significant cell depolarization and enhanced osteogenic differentiation, and these results were closely related to the pathogenic mechanisms of skin aging and heat stroke due to outdoor sun exposure.

scholarly journals Potential Marker Genes for Predicting Adipogenic Differentiation of Mesenchymal Stromal Cells

2019 ◽  
Vol 9 (14) ◽  
pp. 2942 ◽  
Author(s):  
Masami Kanawa ◽  
Akira Igarashi ◽  
Katsumi Fujimoto ◽  
Veronica Sainik Ronald ◽  
Yukihito Higashi ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Expression Profiles ◽  
Adipogenic Differentiation ◽  
Expression Patterns ◽  
Marker Genes ◽  
Mrna Levels ◽  
Differentiation Potential ◽  
Potential Marker ◽  
Promising Source

Mesenchymal stromal cells (MSCs) are a promising source for tissue engineering of soft connective tissues. However, the differentiation capacity of MSCs varies among individual cell lines. Here, we show marker genes to predict the adipogenic potential of MSCs. To clarify the correlation between gene expression patterns before adipogenic induction and the differentiation level of MSCs after differentiation, we compared mRNA levels of 95 genes and glycerol-3-phosphate dehydrogenase (GPDH) activities in 15 MSC lines (five jaw and 10 ilium MSCs) from 15 donors. Expression profiles of 22 genes before differentiation significantly correlated with GPDH activities after differentiation. Expression levels of 11 out of the 22 genes in highly potent ilium MSCs were at least three times higher compared with jaw MSCs, which have limited differentiation potential. Furthermore, three-dimensional scatter plot for mRNA expression of ITGA5, CDKN2D, and CD74 could completely distinguish highly potent MSCs from poorly potent MSCs for adipogenesis. The treatment of MSC cultures with the anti-ITGA5 antibody reduced adipogenic differentiation of MSCs. Collectively, these results suggest that the three genes play a role in adipogenesis before induction and can serve as predictors to select potent MSCs for adipogenic differentiation.

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