Latest advances to enhance the therapeutic potential of mesenchymal stromal cells for the treatment of immune-mediated diseases

Ceruso, Angela; Gonzalez‐Pujana, Ainhoa; Igartua, Manoli; Santos‐Vizcaíno, Edorta; Hernández, Rosa María

doi:10.1007/s13346-021-00934-5

Cited by 8 publications

(7 citation statements)

References 135 publications

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“…14 MSCs possess immunomodulatory properties, making them resistant to recipient immune responses, thus preventing rejection. [15][16][17] Several preclinical studies have shown that MSCs possess intrinsic tumor suppressive properties, including the ability to inhibit cancer cell proliferation, induce apoptosis, and suppress tumor angiogenesis, [18][19][20][21][22][23][24] which makes them more attractive as universal anticancer therapeutic. MSCs have inherent tumor-tropism capability, making them a potent vehicle for selective delivery to tumors.…”

Section: Prominent Intrinsic Properties Of Msc As a Versatile Tumor D...mentioning

confidence: 99%

Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle

Taheri,

Tehrani,

Dehghani

et al. 2024

Medicinal Research Reviews

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Targeting actionable mutations in oncogene‐driven cancers and the evolution of immuno‐oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells (MSCs) possess favorable characteristics for cellular therapy, including their hypoimmune nature, inherent tumor‐tropism property, straightforward isolation, and multilineage differentiation potential. MSCs can be loaded with various chemotherapeutics and oncolytic viruses. The combination of these intrinsic features with the possibility of genetic manipulation makes them a versatile tumor delivery vehicle that can be used for in vivo selective tumor delivery of various chemotherapeutic and biological therapeutics. MSCs can be used as biofactory for the local production of chemical or biological anticancer agents at the tumor site. MSC‐mediated immunotherapy could facilitate the sustained release of immunotherapeutic agents specifically at the tumor site, and allow for the achievement of therapeutic concentrations without the need for repetitive systemic administration of high therapeutic doses. Despite the enthusiasm evoked by preclinical studies that used MSC in various cancer therapy approaches, the translation of MSCs into clinical applications has faced serious challenges. This manuscript, with a critical viewpoint, reviewed the preclinical and clinical studies that have evaluated MSCs as a selective tumor delivery tool in various cancer therapy approaches, including gene therapy, immunotherapy, and chemotherapy. Then, the novel nanotechnology and bioengineering approaches that can improve the potency of MSC for tumor targeting and overcoming challenges related to their low localization at the tumor sites are discussed.

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Section: Prominent Intrinsic Properties Of Msc As a Versatile Tumor D...mentioning

confidence: 99%

Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle

Taheri,

Tehrani,

Dehghani

et al. 2024

Medicinal Research Reviews

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“…The cohabitation of ASCs with pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IFN-ɤ, IL-6, IL-1β, and/or IL-17 can potentiate their effectiveness for inflammatory diseases [ 53 , 100 , 101 ]. Numerous investigators (Table 1 ) assessed the immunogenicity and/or immunosuppressive properties of hASCs after treatment with pro-inflammatory cytokine(s) [ 6 , 13 , 14 , 22 , 27 , 61 , 67 , 85 , 93 , 102 – 121 ] or TLR agonist (s) [ 122 – 129 ].…”

Section: Asc Priming/licensing/preconditioningmentioning

confidence: 99%

“…Hypoxia preconditioning generates ASCs with improved therapeutic immunosuppression [ 68 , 71 , 101 , 130 ]. One of the suggested mechanisms that mediate the enhanced MSC biology and function in hypoxia is the induced expression of hypoxia inducible factor 1 alpha [ 100 , 135 ] and the production of various growth factors, such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), or insulin-like growth factor (IGF) [ 9 ]. Additionally, hypoxic ASCs were able to upregulate strongly the expression of the immunomodulatory molecules IDO and PD-L1 upon stimulation with IFN-ɤ and TNF-α [ 71 ].…”

Section: Asc Priming/licensing/preconditioningmentioning

confidence: 99%

“…Thus, cultivation of MSCs in three-dimensional (3D) systems, such as low attachment surfaces, hydrogels, or scaffolds, to resemble the in vivo spatial organization with increased cell–cell and cell–matrix interactions, have gained attention [ 171 , 179 ]. The methods to generate 3D MSC spheroids, including ASC ones, and the limitation and challenges of different MSC spheroid generation platforms have been recently reviewed [ 171 , 180 ].Enhanced therapeutic and anti-inflammatory mechanisms have been reported in different preclinical models treated with human ASCs cultured by a 3D strategy [ 86 , 100 , 178 , 181 – 190 ].…”

Section: Asc-related Parametersmentioning

confidence: 99%

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Factors Defining Human Adipose Stem/Stromal Cell Immunomodulation in Vitro

Mahmoud,

Abdel-Rasheed,

Galal

et al. 2023

Stem Cell Rev and Rep

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Human adipose tissue-derived stem/stromal cells (hASCs) are adult multipotent mesenchymal stem/stromal cells with immunomodulatory capacities. Here, we present up-to-date knowledge on the impact of different experimental and donor-related factors on hASC immunoregulatory functions in vitro. The experimental determinants include the immunological status of hASCs relative to target immune cells, contact vs. contactless interaction, and oxygen tension. Factors such as the ratio of hASCs to immune cells, the cellular context, the immune cell activation status, and coculture duration are also discussed. Conditioning of hASCs with different approaches before interaction with immune cells, hASC culture in xenogenic or xenofree culture medium, hASC culture in two-dimension vs. three-dimension with biomaterials, and the hASC passage number are among the experimental parameters that greatly may impact the hASC immunosuppressive potential in vitro, thus, they are also considered. Moreover, the influence of donor-related characteristics such as age, sex, and health status on hASC immunomodulation in vitro is reviewed. By analysis of the literature studies, most of the indicated determinants have been investigated in broad non-standardized ranges, so the results are not univocal. Clear conclusions cannot be drawn for the fine-tuned scenarios of many important factors to set a standard hASC immunopotency assay. Such variability needs to be carefully considered in further standardized research. Importantly, field experts’ opinions may help to make it clearer. Graphical Abstract Parameters that promote ASC immunosuppression on immune cells. Activation of immune cells induces their proliferation and differentiation and presence of ASCs modulates/suppresses such consequences. Augmented immunosuppressive effects of ASCs can be introduced in direct contact with the immune cells and via complementing the repeatedly reported experimental settings (texts in grey shapes). Abbreviations: ASCs: adipose tissue-derived stem/stromal cells, IFN-ɤ: Interferon gamma, MLR: Mixed lymphocyte reaction, TNF: Tumor necrosis factor.

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“…MSCs are pluripotent stem cells with anti-inflammatory and immune tolerance potential (31), which were first identified in the bone marrow stroma where supported the development and differentiation of hematopoietic stem cells. In recent years, with research advances, MSCs have been increasingly used in clinical practice given their immunosuppressive functions and tissue repair ability (32). Hence, stem cell therapy is another medical revolution that may be considered after drug therapy and surgical treatment.…”

Section: Different Immunoregulation Capability Of Mscs From Various Originsmentioning

confidence: 99%

Immunomodulatory Effects of Mesenchymal Stem Cells on Drug-Induced Acute Kidney Injury

et al. 2021

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Drug-induced nephrotoxicity is an important and increasing cause of acute kidney injury (AKI), which accounts for approximately 20% of hospitalized patients. Previous reviews studies on immunity and AKI focused mainly on ischemia-reperfusion (IR), whereas no systematic review addressing drug-induced AKI and its related immune mechanisms is available. Recent studies have provided a deeper understanding on the mechanisms of drug-induced AKI, among which acute tubular interstitial injury induced by the breakdown of innate immunity was reported to play an important role. Emerging research on mesenchymal stem cell (MSC) therapy has revealed its potential as treatment for drug-induced AKI. MSCs can inhibit kidney damage by regulating the innate immune balance, promoting kidney repair, and preventing kidney fibrosis. However, it is important to note that there are various sources of MSCs, which impacts on the immunomodulatory ability of the cells. This review aims to address the immune pathogenesis of drug-induced AKI versus that of IR-induced AKI, and to explore the immunomodulatory effects and therapeutic potential of MSCs for drug-induced AKI.

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Latest advances to enhance the therapeutic potential of mesenchymal stromal cells for the treatment of immune-mediated diseases

Cited by 8 publications

References 135 publications

Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle

Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle

Factors Defining Human Adipose Stem/Stromal Cell Immunomodulation in Vitro

Immunomodulatory Effects of Mesenchymal Stem Cells on Drug-Induced Acute Kidney Injury

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