Secretome of Mesenchymal Bone Marrow Stem Cells: Is It Immunosuppressive or Proinflammatory?

Киселевский, М. В.; Vlasenko, R. Ya.; Stepanyan, N. G.; Шубина, И. Ж.; Ситдикова, С. М.; Киргизов, К. И.; Варфоломеева, С. Р.

doi:10.1007/s10517-021-05371-5

Cited by 19 publications

(10 citation statements)

References 21 publications

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“…In IVDD, BMSCs are the most studied intervention among MSCs from other sources. Cytokine profiling of BMSCs, however, revealed intensive production of proinflammatory cytokines IL-6 and IL-8 (Kiselevskii et al, 2021), which may contradict the report that MSCs induce anti-inflammatory effects (Marimuthu and Pushpa Rani, 2021). In addition, BMSCs aid the expression of vascular endothelial growth factor (VEGF) to promote angiogenesis under hypoxic conditions (Archacka et al, 2021).…”

Section: Bmscsmentioning

confidence: 90%

Application of mesenchymal stem cell-derived exosomes from different sources in intervertebral disc degeneration

Xia

Yang²,

Hou³

et al. 2022

Front. Bioeng. Biotechnol.

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Intervertebral disc degeneration (IVDD) is a main cause of lower back pain, leading to psychological and economic burdens to patients. Physical therapy only delays pain in patients but cannot eliminate the cause of IVDD. Surgery is required when the patient cannot tolerate pain or has severe neurological symptoms. Although surgical resection of IVD or decompression of the laminae eliminates the diseased segment, it damages adjacent normal IVD. There is also a risk of re-protrusion after IVD removal. Cell therapy has played a crucial role in the development of regenerative medicine. Cell transplantation promotes regeneration of degenerative tissue. However, owing to the lack of vascular structure in IVD, sufficient nutrients cannot be provided for transplanted mesenchymal stem cells (MSCs). In addition, dead cells release harmful substances that aggravate IVDD. Extracellular vesicles (EVs) have been extensively studied as an emerging therapeutic approach. EVs generated by paracrine MSCs retain the potential of MSCs and serve as carriers to deliver their contents to target cells to regulate target cell activity. Owing to their double-layered membrane structure, EVs have a low immunogenicity and no immune rejection. Therefore, EVs are considered an emerging therapeutic modality in IVDD. However, they are limited by mass production and low loading rates. In this review, the structure of IVD and advantages of EVs are introduced, and the application of MSC-EVs in IVDD is discussed. The current limitations of EVs and future applications are described.

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Section: Bmscsmentioning

confidence: 90%

Application of mesenchymal stem cell-derived exosomes from different sources in intervertebral disc degeneration

Xia

Yang²,

Hou³

et al. 2022

Front. Bioeng. Biotechnol.

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“…The cytokine secretion profiles of MSCs derived from different sources and cultured under different conditions still contain contradictions. Some studies have reported that MSCs do not secrete cytokines such as IL-4 and IL-10 under normal conditions [ 38 ] and can detect only inflammatory conditions and the presence of cytokines [ 39 ]. However, studies showing that amniotic fluid and adipose tissue-derived MSCs secrete cytokines such as IL-4, IL-6, and IL-10 are also available in the literature [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

2D and 3D cultured human umbilical cord-derived mesenchymal stem cell-conditioned medium has a dual effect in type 1 diabetes model in rats: immunomodulation and beta-cell regeneration

et al. 2022

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Background Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease characterized by the irreversible destruction of insulin-producing β-cells in pancreatic islets. Helper and cytotoxic T-cells and cytokine production, which is impaired by this process, take a synergetic role in β-cell destruction, and hyperglycemia develops due to insulin deficiency in the body. Mesenchymal stem cells (MSCs) appear like an excellent therapeutic tool for autoimmune diseases with pluripotent, regenerative, and immunosuppressive properties. Paracrine factors released from MSCs play a role in immunomodulation by increasing angiogenesis and proliferation and suppressing apoptosis. In this context, the study aims to investigate the therapeutic effects of MSC’s secretomes by conditioned medium (CM) obtained from human umbilical cord-derived MSCs cultured in 2-dimensional (2D) and 3-dimensional (3D) environments in the T1D model. Methods First, MSCs were isolated from the human umbilical cord, and the cells were characterized. Then, two different CMs were prepared by culturing MSCs in 2D and 3D environments. The CM contents were analyzed in terms of total protein, IL-4, IL-10, IL-17, and IFN-λ. In vivo studies were performed in Sprague-Dawley-type rats with an autoimmune T1D model, and twelve doses of CM were administered intraperitoneally for 4 weeks within the framework of a particular treatment model. In order to evaluate immunomodulation, the Treg population was determined in lymphocytes isolated from the spleen after sacrification, and IL-4, IL-10, IL-17, and IFN-λ cytokines were analyzed in serum. Finally, β-cell regeneration was evaluated immunohistochemically by labeling Pdx1, Nkx6.1, and insulin markers, which are critical for the formation of β-cells. Results Total protein and IL-4 levels were higher in 3D-CM compared to 2D-CM. In vivo results showed that CMs induce the Treg population and regulate cytokine release. When the immunohistochemical results were evaluated together, it was determined that CM application significantly increased the rate of β-cells in the islets. This increase was at the highest level in the 3D-CM applied group. Conclusion The dual therapeutic effect of MSC-CM on immunomodulation and homeostasis/regeneration of β-cells in the T1D model has been demonstrated. Furthermore, this effect could be improved by using 3D scaffolds for culturing MSCs while preparing CM.

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“…С появлением и развитием тканевой инженерии ГГ стали использовать для восстановления и регенерации различных тканей и органов [1]. Мезенхимальные мультипотентные (стволовые) стромальные клетки (ММСК) применяют для регенерации тканей, лечения и профилактики цитокинового шторма при COVID-19 и реакции «трансплантат против хозяина», а также для стимуляции гемопоэза при аллогенной трансплантации стволовых гемопоэтических клеток [2][3][4][5]. В отличие от рутинного культивирования использование ГГ позволяет создавать 3D-скаффолды, заселенные ММСК, что дает возможность локализовать эти клетки в области тканей-мишеней [6].…”

Section: Introductionunclassified

Efficiency of accelerated electron beam sterilization of a hydrogel for 3D cultivation of mesenchymal multipotent cells

Bystrov

Новрузов

Potapnev³

et al. 2022

Rossijskij bioterapevtičeskij žurnal

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Background. Hydrogels are promising for use in tissue engineering for the restoration and regeneration of various tissues, since they are able to perform the functions of bulk scaffolds, providing the formation of 3D cell structures. Population of such scaffolds with autologous or heterogeneous mesenchymal multipotent stromal cells in vitro makes it possible to localize these cells in the area of target tissues after implantation in a patient. One of the difficult tasks is the choice of the method and mode of sterilization of the hydrogel, which does not change its properties.Aim. Study of the effectiveness of hydrogel sterilization by an accelerated electron beam in various modes, changes in the structure and biocompatibility of the scaffold, to assess the prospects for its use for medical purposes, including as a platform for mesenchymal stromal cells.Materials and methods. We used a hydrogel based on 4 % solutions of sodium alginate and sodium salt of carboxymethyl cellulose, cross-linked with calcium chloride, which was developed, obtained and provided for our research by the team of the Research and Educational Center for Biomedical Engineering of the National University of Science and Technology “MISIS”. Hydrogel samples loaded with Escherichia coli, Lactobacillus acidophilus, Saccharomyces cerevisiae were subjected to electron beam treatment in the range of 5–100 kGy. After electron beam treatment of hydrogel, the presence of living microorganisms and its structure were evaluated by IR-Fourier spectroscopy, as well as the phenotype and formation of 3D structures by mesenchymal multipotent cells.Results. It was found that the treatment of hydrogels with an electron beam at a mode of 25 kGy ensures the death of microorganisms, but does not destroy the structure of the hydrogel and does not inhibit the ability to form capillary-like structures by mesenchymal multipotent cells.Conclusion. Treatment with an accelerated electron beam at a 25 kGy can be used to sterilize hydrogels to obtain bulk scaffolds for cell engineering implants.

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Secretome of Mesenchymal Bone Marrow Stem Cells: Is It Immunosuppressive or Proinflammatory?

Cited by 19 publications

References 21 publications

Application of mesenchymal stem cell-derived exosomes from different sources in intervertebral disc degeneration

Application of mesenchymal stem cell-derived exosomes from different sources in intervertebral disc degeneration

2D and 3D cultured human umbilical cord-derived mesenchymal stem cell-conditioned medium has a dual effect in type 1 diabetes model in rats: immunomodulation and beta-cell regeneration

Efficiency of accelerated electron beam sterilization of a hydrogel for 3D cultivation of mesenchymal multipotent cells

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