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

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.

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 The Identification of Marker Genes for Predicting the Osteogenic Differentiation Potential of Mesenchymal Stromal Cells

2021 ◽  
Vol 43 (3) ◽  
pp. 2157-2166
Author(s):  
Masami Kanawa ◽  
Akira Igarashi ◽  
Katsumi Fujimoto ◽  
Tania Saskianti ◽  
Ayumu Nakashima ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Marker Genes ◽  
Mrna Levels ◽  
Differentiation Potential ◽  
Alp Activity ◽  
Osteogenic Induction ◽  
Promising Source

Mesenchymal stromal cells (MSCs) have the potential to differentiate into a variety of mature cell types and are a promising source of regenerative medicine. The success of regenerative medicine using MSCs strongly depends on their differentiation potential. In this study, we sought to identify marker genes for predicting the osteogenic differentiation potential by comparing ilium MSC and fibroblast samples. We measured the mRNA levels of 95 candidate genes in nine ilium MSC and four fibroblast samples before osteogenic induction, and compared them with alkaline phosphatase (ALP) activity as a marker of osteogenic differentiation after induction. We identified 17 genes whose mRNA expression levels positively correlated with ALP activity. The chondrogenic and adipogenic differentiation potentials of jaw MSCs are much lower than those of ilium MSCs, although the osteogenic differentiation potential of jaw MSCs is comparable with that of ilium MSCs. To select markers suitable for predicting the osteogenic differentiation potential, we compared the mRNA levels of the 17 genes in ilium MSCs with those in jaw MSCs. The levels of 7 out of the 17 genes were not substantially different between the jaw and ilium MSCs, while the remaining 10 genes were expressed at significantly lower levels in jaw MSCs than in ilium MSCs. The mRNA levels of the seven similarly expressed genes were also compared with those in fibroblasts, which have little or no osteogenic differentiation potential. Among the seven genes, the mRNA levels of IGF1 and SRGN in all MSCs examined were higher than those in any of the fibroblasts. These results suggest that measuring the mRNA levels of IGF1 and SRGN before osteogenic induction will provide useful information for selecting competent MSCs for regenerative medicine, although the effectiveness of the markers is needed to be confirmed using a large number of MSCs, which have various levels of osteogenic differentiation potential.

scholarly journals Identification of ALP+/CD73+ defining markers for enhanced osteogenic potential in human adipose-derived mesenchymal stromal cells by mass cytometry

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Daisy D. Canepa ◽  
Elisa A. Casanova ◽  
Eirini Arvaniti ◽  
Vinko Tosevski ◽  
Sonja Märsmann ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Osteogenic Differentiation ◽  
Single Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Osteogenic Potential ◽  
Single Cell Level ◽  
Cellular Composition ◽  
Cell Level ◽  
Differentiation Potential

Abstract Background The impressive progress in the field of stem cell research in the past decades has provided the ground for the development of cell-based therapy. Mesenchymal stromal cells obtained from adipose tissue (AD-MSCs) represent a viable source for the development of cell-based therapies. However, the heterogeneity and variable differentiation ability of AD-MSCs depend on the cellular composition and represent a strong limitation for their use in therapeutic applications. In order to fully understand the cellular composition of MSC preparations, it would be essential to analyze AD-MSCs at single-cell level. Method Recent advances in single-cell technologies have opened the way for high-dimensional, high-throughput, and high-resolution measurements of biological systems. We made use of the cytometry by time-of-flight (CyTOF) technology to explore the cellular composition of 17 human AD-MSCs, interrogating 31 markers at single-cell level. Subcellular composition of the AD-MSCs was investigated in their naïve state as well as during osteogenic commitment, via unsupervised dimensionality reduction as well as supervised representation learning approaches. Result This study showed a high heterogeneity and variability in the subcellular composition of AD-MSCs upon isolation and prolonged culture. Algorithm-guided identification of emerging subpopulations during osteogenic differentiation of AD-MSCs allowed the identification of an ALP+/CD73+ subpopulation of cells with enhanced osteogenic differentiation potential. We could demonstrate in vitro that the sorted ALP+/CD73+ subpopulation exhibited enhanced osteogenic potential and is moreover fundamental for osteogenic lineage commitment. We finally showed that this subpopulation was present in freshly isolated human adipose-derived stromal vascular fractions (SVFs) and that could ultimately be used for cell therapies. Conclusion The data obtained reveal, at single-cell level, the heterogeneity of AD-MSCs from several donors and highlight how cellular composition impacts the osteogenic differentiation capacity. The marker combination (ALP/CD73) can not only be used to assess the differentiation potential of undifferentiated AD-MSC preparations, but also could be employed to prospectively enrich AD-MSCs from the stromal vascular fraction of human adipose tissue for therapeutic applications.

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