Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases

Zhao, Qinjun; Ren, Hongzheng; Han, Zhongchao

doi:10.1016/j.jocit.2014.12.001

Cited by 257 publications

(219 citation statements)

References 185 publications

(144 reference statements)

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“…This is consistent with several previous studies demonstrating that MSCs do not evoke an immune response because of lack of expression of HLA class I and II molecules and costimulatory molecules such as CD40, 80, and 86, which are responsible for immune response (47). …”

Section: Discussionsupporting

confidence: 93%

Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of Anticancer Drug Through True Active Tumor Targeting

Layek

Sadhukha

Panyam

et al. 2018

Molecular Cancer Therapeutics

101

107

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Tumor-targeted drug delivery has the potential to improve therapeutic efficacy and mitigate non-specific toxicity of anticancer drugs. However, current drug delivery approaches rely on inefficient passive accumulation of the drug carrier in the tumor. We have developed a unique, truly active tumor targeting strategy that relies on engineering mesenchymal stem cells (MSCs) with drug-loaded nanoparticles. Our studies using the A549 orthotopic lung tumor model show that nano-engineered MSCs carrying the anticancer drug paclitaxel (PTX) home to tumors and create cellular drug depots that release the drug payload over several days. Despite significantly lower doses of PTX, nano-engineered MSCs resulted in significant inhibition of tumor growth and superior survival. Anticancer efficacy of nano-engineered MSCs was confirmed in immunocompetent C57BL/6 albino female mice bearing orthotopic Lewis Lung Carcinoma (LL/2-luc) tumors. Further, at doses that resulted in equivalent therapeutic efficacy, nano-engineered MSCs had no effect on white blood cell count whereas PTX solution and PTX nanoparticle treatments caused leukopenia. Biodistribution studies showed that nano–engineered MSCs resulted in greater than 9–fold higher AUClung of PTX (1.5 µg.day/g) than PTX solution and nanoparticles (0.2 and 0.1 µg.day/g tissue, respectively) in the target lung tumors. Furthermore, the lung-to-liver and the lung-to-spleen ratios of PTX were several folds higher for nano-engineered MSCs relative to those for PTX solution and nanoparticle groups, suggesting that nano–engineered MSCs demonstrate significantly less off-target deposition. In summary, our results demonstrate that nano-engineered MSCs can serve as an efficient carrier for tumor specific drug delivery and significantly improved anti–cancer efficacy of conventional chemotherapeutic drugs.

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Section: Discussionsupporting

confidence: 93%

Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of Anticancer Drug Through True Active Tumor Targeting

Layek

Sadhukha

Panyam

et al. 2018

Molecular Cancer Therapeutics

101

107

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“…The results also indicate that the suppression of MSCs is associated with or mediated by PGE2, which has been previously observed for UCMSCs (Kim et al, 2015;Yu et al, 2014). However, many published publications have also suggested the role of other factors (TGFbeta, HGF, PGE 2 , NO, and IDO) in immune modulation by MSCs (Ma et al, 2014;Soleymaninejadian et al, 2012;Zhao et al, 2016).…”

Section: Discussionsupporting

confidence: 81%

Umbilical cord-derived stem cells (ModulatistTM) show strong immunomodulation capacity compared to adipose tissue-derived or bone marrow-derived mesenchymal stem cells

Pham¹,

Vu²,

Phan³

2016

Biomed Res Ther

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Abstract-Introduction:Mesenchymal stem cells (MSCs) show great promise in regenerative medicine. Clinical applications of MSCs have recently increased significantly, especially for immune diseases. Autologous transplantation is considered a safe therapy. However, its main disadvantages are poor stability and quality of MSCs from patient to patient, and labor-intensive and time-consuming culture procedures. Therefore, allogeneic MSC transplantation has recently emerged as a potential replacement for autologous transplantation. "Off the shelf" MSC products, or socalled "stem cell drugs", have rapidly developed; these products have already been approved in various countries, including Canada, Korea and Japan. This study aims to evaluate a new stem cell product or "drug", termed Modulatist TM , derived from umbilical cord mesenchymal stem cells (UCMSCs), which have strong immunomodulatory properties, compared to bone marrow-derived MSCs (BMMSCs) or adipose tissue-derived stem cells (ADSCs). Methods: Modulatist TM was produced from MSCs derived from whole umbilical cord (UC) tissue (which includes Wharton's jelly and UC), according to GMP compliant procedures. Bone marrow-and adipose tissue-derived MSCs were isolated and proliferated in standard conditions, according to GMP compliant procedures. Immunomodulation mediated by MSCs was assessed by allogenic T cell suppression and cytokine release; role of prostaglandin E2 in the immunomodulation was also evaluated. Results: The results showed that Modulatist TM exhibited stronger immunomodulation than BMMSC and ADSC in vitro. Modulatist TM strongly suppressed allogeneic T cells proliferation and decreased cytokine production, compared to BMMSCs and ADSCs. Conclusion: Modulatist TM is a strong immunomodulator and promising MSC product. It may be useful to modulate or treat autoimmune diseases.

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“…The side bone marrow stromal cells critical-sized bone defects dental pulp stem cells effective cell dose extracellular matrix gene-activated matrix hypoxia-inducible factor 1-α intra-arterial intravenous mesenchymal stem cells osteogenesis imperfecta platelet-rich fibrin platelet-rich plasma stromal-derived factor 1 stromal vascular fraction tricalcium phosphate tissue engineering and regenerative medicine toll-like receptors tumor necrosis factor-α vascular endothelial growth factor initial observations through the study of the proliferative abilities and phenotypic characteristics of CFU-Fs [Caplan and Bruder, 2001;Eslaminejad and Taghiyar, 2010;Eslaminejad et al, 2011;Lotfy et al, 2014;Baker et al, 2015]. MSCs have been widely used in stem cell transplantation, tissue engineering, gene therapy, and immunotherapy [Reiser et al, 2005;Marion and Mao, 2006;Zhao et al, 2016]. These cells express CD105, CD73, and CD90, and are not able to express CD45, CD34, CD14, or CD11b, CD79α or CD19 antigens.…”

mentioning

confidence: 99%

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Oryan

Kamali²,

Moshiri³

et al. 2017

Cells Tissues Organs

291

204

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Healing and regeneration of bone injuries, particularly those that are associated with large bone defects, are a complicated process. There is growing interest in the application of osteoinductive and osteogenic growth factors and mesenchymal stem cells (MSCs) in order to significantly improve bone repair and regeneration. MSCs are multipotent stromal stem cells that can be harvested from many different sources and differentiated into a variety of cell types, such as preosteogenic chondroblasts and osteoblasts. The effectiveness of MSC therapy is dependent on several factors, including the differentiating state of the MSCs at the time of application, the method of their delivery, the concentration of MSCs per injection, the vehicle used, and the nature and extent of injury, for example. Tissue engineering and regenerative medicine, together with genetic engineering and gene therapy, are advanced options that may have the potential to improve the outcome of cell therapy. Although several in vitro and in vivo investigations have suggested the potential roles of MSCs in bone repair and regeneration, the mechanism of MSC therapy in bone repair has not been fully elucidated, the efficacy of MSC therapy has not been strongly proven in clinical trials, and several controversies exist, making it difficult to draw conclusions from the results. In this review, we update the recent advances in the mechanisms of MSC action and the delivery approaches in bone regenerative medicine. We will also review the most recent clinical trials to find out how MSCs may be beneficial for treating bone defects.

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Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases

Cited by 257 publications

References 185 publications

Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of Anticancer Drug Through True Active Tumor Targeting

Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of Anticancer Drug Through True Active Tumor Targeting

Umbilical cord-derived stem cells (ModulatistTM) show strong immunomodulation capacity compared to adipose tissue-derived or bone marrow-derived mesenchymal stem cells

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

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