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Effects of a ceramic biomaterial on immune modulatory properties and differentiation potential of human mesenchymal stromal cells of different origin.

ABSTRACT: The aim of this study was to assess the immune modulatory properties of human mesenchymal stromal cells obtained from bone marrow (BM-MSCs), fat (ASCs), and cord blood (CB-MSCs) in the presence of a hydroxyapatite and tricalcium-phosphate (HA/TCP) biomaterial as a scaffold for MSC delivery. In resting conditions, a short-term culture with HA/TCP did not modulate the anti-apoptotic and suppressive features of the various MSC types toward T, B, and NK cells; in addition, when primed with inflammatory cytokines, MSCs similarly increased their suppressive capacities in the presence or absence of HA/TCP. The long-term culture of BM-MSCs with HA/TCP induced an osteoblast-like phenotype with upregulation of OSTERIX and OSTEOCALCIN, similar to what was obtained with dexamethasone and, to a higher extent, with bone morphogenetic protein 4 (BMP-4) treatment. MSC-derived osteoblasts did not trigger immune cell activation, but were less efficient than undifferentiated MSCs in inhibiting stimulated T and NK cells. Interestingly, their suppressive machinery included not only the activation of indoleamine-2,3 dioxygenase (IDO), which plays a central role in T-cell inhibition, but also cyclooxygenase-2 (COX-2) that was not significantly involved in the immune modulatory effect of human undifferentiated MSCs. Since COX-2 is significantly involved in bone healing, its induction by HA/TCP could also contribute to the therapeutic activity of MSCs for bone tissue engineering.

SUBMITTER: Bassi G

PROVIDER: S-EPMC4334097 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Effects of a ceramic biomaterial on immune modulatory properties and differentiation potential of human mesenchymal stromal cells of different origin.

Bassi Giulio G Guilloton Fabien F Menard Cedric C Di Trapani Mariano M Deschaseaux Frederic F Sensebé Luc L Schrezenmeier Hubert H Giordano Rosaria R Bourin Philippe P Dominici Massimo M Tarte Karin K Krampera Mauro M

Tissue engineering. Part A 20141211 3-4

The aim of this study was to assess the immune modulatory properties of human mesenchymal stromal cells obtained from bone marrow (BM-MSCs), fat (ASCs), and cord blood (CB-MSCs) in the presence of a hydroxyapatite and tricalcium-phosphate (HA/TCP) biomaterial as a scaffold for MSC delivery. In resting conditions, a short-term culture with HA/TCP did not modulate the anti-apoptotic and suppressive features of the various MSC types toward T, B, and NK cells; in addition, when primed with inflammat ...[more]

PMID: 25322665

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Project description:Advanced therapy medicinal products (ATMPs) offer new prospects to improve the treatment of conditions with unmet medical needs. Kidney diseases are a current major health concern with an increasing global prevalence. Chronic renal failure appears after many years of impairment, which opens a temporary window to apply novel therapeutic approaches to delay or halt disease progression. The immunomodulatory, anti-inflammatory, and pro-regenerative properties of mesenchymal stromal cells (MSCs) have sparked interest for their use in cell-based regenerative therapies. Currently, several early-phase clinical trials have been completed and many are ongoing to explore MSC safety and efficacy in a wide range of nephropathies. However, one of the current roadblocks to the clinical translation of MSC therapies relates to the lack of standardization and harmonization of MSC manufacturing protocols, which currently hinders inter-study comparability. Studies have shown that cell culture processing variables can have significant effects on MSC phenotype and functionality, and these are highly variable across laboratories. In addition, heterogeneity within MSC populations is another obstacle. Furthermore, MSCs may be isolated from several sources which adds another variable to the comparative assessment of outcomes. There is now a growing body of literature highlighting unique and distinctive properties of MSCs according to the tissue origin, and that characteristics such as donor, age, sex and underlying medical conditions may alter the therapeutic effect of MSCs. These variables must be taken into consideration when developing a cell therapy product. Having an optimal scale-up strategy for MSC manufacturing is critical for ensuring product quality while minimizing costs and time of production, as well as avoiding potential risks. Ideally, optimal scale-up strategies must be carefully considered and identified during the early stages of development, as making changes later in the bioprocess workflow will require re-optimization and validation, which may have a significant long-term impact on the cost of the therapy. This article provides a summary of important cell culture processing variables to consider in the scale-up of MSC manufacturing as well as giving a comprehensive review of tissue of origin-specific biological characteristics of MSCs and their use in current clinical trials in a range of renal pathologies.

Project description:BackgroundIn most patients with aplastic anemia (AA), the diagnosis is limited to a description of the symptoms. Lack of understanding of the underlying pathophysiological mechanisms causing bone marrow failure (BMF), hampers tailored treatment. In these patients, auto-immune cell-mediated destruction of the bone marrow is often presumed to be the causative mechanism. The status of the bone marrow microenvironment, particularly the mesenchymal stromal cell (MSC) component, was recently suggested as a potential player in the pathophysiology of AA. Therefore, functional, and immune modulatory characteristics of bone marrow MSCs might represent important parameters for AA.ObjectiveTo conduct a systematic review to evaluate in vitro functional properties of MSCs derived from patients with AA compared to healthy controls.MethodsAccording to PRISMA guidelines, a comprehensive search strategy was performed by using online databases (Pubmed, ISI Web of Science, Embase, and the Cochrane Library). Studies reporting on phenotypical characterization, proliferation potential, differentiation capacity, immunomodulatory potential, and ability to support hematopoiesis were identified and screened using the Rayyan software tool.Results23 articles were included in this systematic review, describing a total of 324 patients with AA and 285 controls. None of the studies identified a significant difference in expression of any MSC surface marker between both groups. However, AA-MSCs showed a decreased proliferation potential, an increased tendency to differentiate into the adipogenic lineage and decreased propensity towards osteogenic differentiation. Importantly, AA-MSCs show reduced capacity of immunosuppression and hematopoietic support in comparison to healthy controls.ConclusionWe conclude that there are indications for a contribution of MSCs in the pathophysiology of AA. However, the current evidence is of poor quality and requires better defined study populations in addition to a more robust methodology to study MSC biology at a cellular and molecular level. Future studies on bone marrow microenvironment should aim at elucidating the interaction between MSCs, hematopoietic stem cells (HSCs) and immune cells to identify impairments associated with/causing BMF in patients with AA.

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Effects of a ceramic biomaterial on immune modulatory properties and differentiation potential of human mesenchymal stromal cells of different origin.

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Effects of a ceramic biomaterial on immune modulatory properties and differentiation potential of human mesenchymal stromal cells of different origin.

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