Prospectively isolated mesenchymal stem/stromal cells are enriched in the CD73+ population and exhibit efficacy after transplantation

Suto, Eriko Grace; Mabuchi, Yo; Suzuki, Nobuharu; Suzuki, Kôji; Ogata, Yusuke; Taguchi, Miyu; Muneta, Takeshi; Sekiya, Ichiro; Akazawa, Chihiro

doi:10.1038/s41598-017-05099-1

Cited by 46 publications

(61 citation statements)

References 53 publications

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“…In a recent study, sorting MSC sub-populations based on CD73 + expression has produced cells with greater self-renewal and differentiation properties. 108 These sorted cells (CD73 + ) exhibited high levels of colony forming unit ability in contrast with an absence observed with CD73cells.…”

Section: Msc Enrichmentmentioning

confidence: 94%

Mesenchymal stromal cell therapy for liver diseases

Alfaifi

Eom

Newsome

et al. 2018

Journal of Hepatology

168

148

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The therapeutic potential of mesenchymal stromal cells (MSCs) in the treatment of liver fibrosis is predominantly based on their immunosuppressive properties, and their ability to secrete various trophic factors. This potential has been investigated in clinical and preclinical studies. Although the therapeutic mechanisms of MSC transplantation are still not fully characterised, accumulating evidence has revealed that various trophic factors secreted by MSCs play key therapeutic roles in regeneration by alleviating inflammation, apoptosis, and fibrosis as well as stimulating angiogenesis and tissue regeneration in damaged liver. In this review, we summarise the safety, efficacy, potential transplantation routes and therapeutic effects of MSCs in patients with liver fibrosis. We also discuss some of the key strategies to enhance the functionality of MSCs, which include sorting and/or priming with factors such as cytokines, as well as genetic engineering.

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Section: Msc Enrichmentmentioning

confidence: 94%

Mesenchymal stromal cell therapy for liver diseases

Alfaifi

Eom

Newsome

et al. 2018

Journal of Hepatology

168

148

View full text Add to dashboard Cite

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“…In the clinical application of cell-based therapies, cell surface markers such as CD34 (a marker of hematopoietic stem cells), CD73, CD90, and CD105 (a marker of mesenchymal stem cells, MSCs), which may represent the targeting ability of cell tissue products, have been analyzed and have shown promise as stable and effective treatments for damaged tissues [11]. Although several markers, such as myogenin, MyoD, and desmin, have been reported as markers of myoblasts [12,13], the cell surface marker CD56 has been thought to be more useful for evaluation of myoblast because of its simple method for measurement.…”

Section: Introductionmentioning

confidence: 99%

Role and therapeutic effects of skeletal muscle-derived non-myogenic cells in a rat myocardial infarction model

et al. 2020

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Background: Transplantation of skeletal myoblast sheets is a promising strategy for the treatment of heart failure, and its therapeutic effects have already been proven in both animal disease models and clinical trials. Myoblast sheets reportedly demonstrate their therapeutic effects by producing many paracrine factors. Although the quality of processed cells for transplantation can be evaluated by the positive ratio of CD56, a myoblast marker, it is unclear which cell populations from isolated cells produce paracrine factors that have an impact on therapeutic effects, and whether these therapeutic effects are closely correlated with CD56-positive cells isolated from the skeletal muscle is also unclear. Therefore, we hypothesized that CD56-negative cells as well as CD56-positive cells isolated from the skeletal muscle produce paracrine factors and have therapeutic effects in skeletal muscle-derived cell sheet therapy for heart failure. Methods: Cell surface and intracellular markers of CD56-negative non-myogenic cells (NMCs) and CD56-positive myoblasts were evaluated. We also analyzed cytokine expression, tube formation ability, and stem cell mobilization in both cell populations. Finally, we assessed the therapeutic effects of the cell populations in a rat myocardial infarction model.Results: Analysis of cell surface and intracellular markers revealed that CD56-negative NMCs expressed fibroblast markers and a higher level of mesenchymal cell markers, such as CD49b and CD140a, than myoblasts. Both NMCs and myoblasts expressed various cytokines in vitro with different expression patterns. In addition, NMCs induced tube formation (control vs. myoblasts vs. NMCs: 100 ± 11.2 vs. 142 ± 8.3 vs. 198 ± 7.4%) and stem cell mobilization (control vs. myoblasts vs. NMCs: 100 ± 6.8 vs. 210 ± 22.9 vs. 351 ± 36.0%) to a higher degree in vitro than did myoblasts. The effect of NMCs and myoblasts on the improvement of cardiac function and suppression of myocardial fibrosis in rat myocardial infarction model was comparable. Conclusion:These results indicate that NMCs exhibit therapeutic effects in skeletal muscle-derived cell sheet therapy for heart failure. Thus, accurate parameters correlating with therapeutic effects need to be further explored.

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“…CD44 that was expressed by 93% of MSCs from whole V-BMA, 52% of MSCs from concentrated V-BMA and 100% of MSCs from clotted V-BMA regulates and operates in cell adhesion, migration, homing, proliferation and apoptosis and have also a role in stemness properties and maintenance 41,42 . CD73+ positive populations that in our study were expressed only by 64% of MSCs from concentrated V-BMA and by high percentage in the other culture conditions are significantly enriched in clonogenic cells, able to generate CFUs 43 . In our study, this data was confirmed also by the lower CFUs number that was evaluated in MSCs from concentrated V-BMA.…”

Section: Discussionmentioning

confidence: 41%

A Rationale for the Use of Clotted Vertebral Bone Marrow to Aid Tissue Regeneration Following Spinal Surgery

Salamanna

Contartese

Giavaresi

et al. 2020

Sci Rep

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Vertebral body bone marrow aspirate (V-BMA), easily accessible simultaneously with the preparation of the site for pedicle screw insertion during spinal procedures, is becoming an increasingly used cell therapy approach in spinal surgery. However, the main drawbacks for V-BMA use are the lack of a standardized procedure and of a structural texture with the possibility of diffusion away from the implant site. the aim of this study was to evaluate, characterize and compare the biological characteristics of MScs from clotted V-BMA and MScs from whole and concentrate V-BMAs. MScs from clotted V-BMA showed the highest cell viability and growth factors expression (tGf-β, VeGf-A, FGF2), the greatest colony forming unit (CFU) potency, cellular homogeneity, ability to differentiate towards the osteogenic (COL1AI, TNFRSF11B, BGLAP) and chondrogenic phenotype (SOX9) and the lowest ability to differentiate toward the adipogenic lineage (ADIPOQ) in comparison to all the other culture conditions. Additionally, results revealed that MSCs, differently isolated, expressed different level of HOX and TALE signatures and that PBX1 and MEIS3 were down-regulated in MSCs from clotted V-BMA in comparison to concentrated one. The study demonstrated for the first time that the cellular source inside the clotted V-BMA showed the best biological properties, representing an alternative and advanced cell therapy approach for patients undergoing spinal surgery. Bone marrow aspiration is an easy, safe and inexpensive method that makes possible a direct transplantation of mesenchymal stem cells (MSCs), endothelial progenitor cells, hematopoietic stem cells, other progenitor cells, growth factors, e.g. bone morphogenetic proteins (BMPs), platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and several interleukins, into the defect site 1-3. Despite only a very small percentage (0.01-0.001%) of MSCs is found among the totality of mononuclear cells in bone marrow aspirate (BMA), the attendance of non-adherent osteogenic cells and the potential collaboration among BMA cell types in tissue repair suggest that the use of whole BMA, instead of expanded, concentrated and purified MSCs, is preferable for bone cell therapy 4. Recently the use of iliac crest BMA is becoming increasingly trendy also in spinal surgery in order to overcome the problems linked to the harvest and use of iliac crest autograft and/or local autograft (spinous processes, laminae) 5,6. However, several issues of the process need specific attention in order to optimize the efficacy and reduce potential side effects 7. In addition, although bone marrow is commonly aspirated by the iliac crest, during spinal surgery its harvest leads to an increase in operative and rehabilitation time and to further morbidity in the donor site 8. These complications are particularly critical in adolescent idiopathic scoliosis patients who have no pain before surgery and in osteoporotic patients that have a greatest risk of bleeding comp...

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Prospectively isolated mesenchymal stem/stromal cells are enriched in the CD73+ population and exhibit efficacy after transplantation

Cited by 46 publications

References 53 publications

Mesenchymal stromal cell therapy for liver diseases

Mesenchymal stromal cell therapy for liver diseases

Role and therapeutic effects of skeletal muscle-derived non-myogenic cells in a rat myocardial infarction model

A Rationale for the Use of Clotted Vertebral Bone Marrow to Aid Tissue Regeneration Following Spinal Surgery

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