204-LB: The In Vitro Characteristics of Human Islet Cells from Diverse Donors, Coaggregated with Human Mesenchymal Stromal Cells to form “Neo-islets”, Are Consistently Identical: Relevance to Clinical Trials in Diabetic Subjects

COPD is characterised by tissue destruction and inflammation. Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant. In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair. These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD. Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD. However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD. In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research.

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Growth factor and cytokine expression of human mesenchymal stromal cells is not altered in an in vitro model of tissue damage

Cytotherapy ◽

10.3109/14653249.2010.501789 ◽

2010 ◽

Vol 12 (7) ◽

pp. 870-880 ◽

Cited By ~ 13

Author(s):

Katrin Montzka ◽

Tobias Führmann ◽

Jochen Müller-Ehmsen ◽

Michael Wöltje ◽

Gary A. Brook

Keyword(s):

Growth Factor ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Tissue Damage ◽

In Vitro Model ◽

Cytokine Expression ◽

Human Mesenchymal Stromal Cells ◽

Vitro Model

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Is in vivo biodistribution and toxicity assessment of human mesenchymal stromal cells in rodent model relevant to organ targeted clinical trials?

Cytotherapy ◽

10.1016/s1465324921003571 ◽

2021 ◽

Vol 23 (5) ◽

pp. S61

Author(s):

S. Selvaraj ◽

S. K.N. ◽

R. Meenakshi Sundaram ◽

S.R ◽

C. Anbalagan ◽

...

Keyword(s):

Clinical Trials ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Toxicity Assessment ◽

Rodent Model ◽

Human Mesenchymal Stromal Cells ◽

In Vivo Biodistribution

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Human Mesenchymal Stromal Cells are Mechanosensitive to Vibration Stimuli

Journal of Dental Research ◽

10.1177/0022034512465291 ◽

2012 ◽

Vol 91 (12) ◽

pp. 1135-1140 ◽

Cited By ~ 41

Author(s):

I.S. Kim ◽

Y.M. Song ◽

B. Lee ◽

S.J. Hwang

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Type I Collagen ◽

Bone Cells ◽

Type I ◽

Related Factors ◽

Matrix Mineralization ◽

Vibration Signals ◽

Human Mesenchymal Stromal Cells

Low-magnitude high-frequency (LMHF) vibrations have the ability to stimulate bone formation and reduce bone loss. However, the anabolic mechanisms that are mediated by vibration in human bone cells at the cellular level remain unclear. We hypothesized that human mesenchymal stromal cells (hMSCs) display direct osteoblastic responses to LMHF vibration signals. Daily exposure to vibrations increased the proliferation of hMSCs, with the highest efficiency occurring at a peak acceleration of 0.3 g and vibrations at 30 to 40 Hz. Specifically, these conditions promoted osteoblast differentiation through an increase in alkaline phosphatase activity and in vitro matrix mineralization. The effect of vibration on the expression of osteogenesis-related factors differed depending on culture method. hMSCs that underwent vibration in a monolayer culture did not exhibit any changes in the expressions of these genes, while cells in three-dimensional culture showed increased expression of type I collagen, osteoprotegerin, or VEGF, and VEGF induction appeared in 2 different hMSC lines. These results are among the first to demonstrate a dose-response effect upon LMHF stimulation, thereby demonstrating that hMSCs are mechanosensitive to LMHF vibration signals such that they could facilitate the osteogenic process.

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Human mesenchymal stromal cells primed with paclitaxel, apart from displaying anti-tumor activity, maintain their immune regulatory functions in vitro

Cytotherapy ◽

10.1016/j.jcyt.2014.01.414 ◽

2014 ◽

Vol 16 (6) ◽

pp. 868-870 ◽

Cited By ~ 5

Author(s):

Antonella Conforti ◽

Simone Biagini ◽

Nadia Starc ◽

Alessandra Proia ◽

Augusto Pessina ◽

...

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Human Mesenchymal Stromal Cells ◽

Regulatory Functions ◽

Anti Tumor Activity

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Immunological Characterization Of Multipotent Mesenchymal Stromal Cells. The International Society For Cellular Therapy (ISCT) Working Proposal

Blood ◽

10.1182/blood.v122.21.5438.5438 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5438-5438

Author(s):

Mauro Krampera ◽

Jacques Galipeau ◽

Yufang Shi ◽

Karin Tarte ◽

Luc Sensebé

Keyword(s):

Clinical Trials ◽

Mesenchymal Stromal Cells ◽

International Society ◽

Stromal Cells ◽

Quantitative Methods ◽

Multipotent Mesenchymal Stromal Cells ◽

In Vivo Models ◽

Immunological Characterization

Abstract The large number of experimental approaches, culture conditions, qualitative and quantitative methods, and in vitro and in vivo models employed so far to assess immune regulatory properties of multipotent mesenchymal stromal cells (MSC) has led to an excess of literature data that sometimes are poorly comparable, redundant, and even contradictory. Thus, quite paradoxically, the risk is that pre-clinical literature data may become eventually weak and scarcely useful, in both researchers’ and Regulatory Authorities’ opinion, for supporting experimentally specific MSC-based clinical trials aimed at treating autoimmune and inflammatory diseases. However, some data in this field appear more solid and reproducible and may be generally accepted to suggest reproducible immunological assays to quantify the differences in immune modulatory properties of MSCs produced according to Good Manufacturing Practice (GMP). The MSC Committee of the International Society of Cell Therapy (ISCT) released a statement paper in 2006 that established the minimal criteria characterizing human MSC, without focusing particularly on their immunological properties. In the 7 years following the publication of this statement paper, more than 10,000 manuscripts on MSC, and many of them deal with immune regulation. To consolidate the scientific research in this field, the MSC Committee of the ISCT is publishing a working proposal paper aimed at stimulating the general discussion about the need of shared guidelines for the immunological characterization of MSCs for clinical use: 1. A standard immune plasticity assay should be implemented by using IFN-γ + TNF-α as model in vitro priming agent 2. Functional analysis of an expanded cell product may provide mechanistic insights on intra- and inter- study variance in clinical response amongst patients 3. The use of purified responders would be widely practicable and should provide more generalizable guidance on relative functional potency of MSC and as a companion to clinical trials 4. Interrogating the IDO response as part of an in vitro licensing assay should be considered central 5. Conclusions based on xenorecipient animal models on how to conduct clinical trials should be drawn with caution 6. The prospective hypothesis-driven analysis of lymphocyte populations in patients groups treated with MSC should be encouraged 7. Clinical analysis should also include the monitoring of whether injected MSCs are the target of an immune response. Disclosures: No relevant conflicts of interest to declare.

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A double‐virally‐inactivated (Intercept–solvent/detergent) human platelet lysate for in vitro expansion of human mesenchymal stromal cells

Transfusion ◽

10.1111/trf.15251 ◽

2019 ◽

Cited By ~ 7

Author(s):

Lassina Barro ◽

Yu‐Ting Su ◽

Ouada Nebie ◽

Yu‐Wen Wu ◽

Yen‐Hua Huang ◽

...

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Human Platelet ◽

Platelet Lysate ◽

Human Mesenchymal Stromal Cells ◽

In Vitro Expansion ◽

Human Platelet Lysate

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Syndecan-2–positive, Bone Marrow–derived Human Mesenchymal Stromal Cells Attenuate Bacterial-induced Acute Lung Injury and Enhance Resolution of Ventilator-induced Lung Injury in Rats

Anesthesiology ◽

10.1097/aln.0000000000002327 ◽

2018 ◽

Vol 129 (3) ◽

pp. 502-516 ◽

Cited By ~ 12

Author(s):

Claire Masterson ◽

James Devaney ◽

Shahd Horie ◽

Lisa O’Flynn ◽

Laura Deedigan ◽

...

Keyword(s):

Escherichia Coli ◽

Lung Injury ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Arterial Oxygenation ◽

Human Mesenchymal Stromal Cells ◽

Ventilator Induced Lung Injury ◽

Enhanced Resolution ◽

Macrophage Phagocytosis

Abstract What We Already Know about This Topic What This Article Tells Us That Is New Background Human mesenchymal stromal cells demonstrate promise for acute respiratory distress syndrome, but current studies use highly heterogenous cell populations. We hypothesized that a syndecan 2 (CD362)–expressing human mesenchymal stromal cell subpopulation would attenuate Escherichia coli–induced lung injury and enhance resolution after ventilator-induced lung injury. Methods In vitro studies determined whether CD362+ human mesenchymal stromal cells could modulate pulmonary epithelial inflammation, wound healing, and macrophage phagocytosis. Two in vivo rodent studies determined whether CD362+ human mesenchymal stromal cells attenuated Escherichia coli–induced lung injury (n = 10/group) and enhanced resolution of ventilation-induced injury (n = 10/group). Results CD362+ human mesenchymal stromal cells attenuated cytokine-induced epithelial nuclear factor kappa B activation, increased epithelial wound closure, and increased macrophage phagocytosis in vitro. CD362+ human mesenchymal stromal cells attenuated Escherichia coli–induced injury in rodents, improving arterial oxygenation (mean ± SD, 83 ± 9 vs. 60 ± 8 mmHg, P < 0.05), improving lung compliance (mean ± SD: 0.66 ± 0.08 vs. 0.53 ± 0.09 ml · cm H2O−1, P < 0.05), reducing bacterial load (median [interquartile range], 1,895 [100–3,300] vs. 8,195 [4,260–8,690] colony-forming units, P < 0.05), and decreasing structural injury compared with vehicle. CD362+ human mesenchymal stromal cells were more effective than CD362− human mesenchymal stromal cells and comparable to heterogenous human mesenchymal stromal cells. CD362+ human mesenchymal stromal cells enhanced resolution after ventilator-induced lung injury in rodents, restoring arterial oxygenation (mean ± SD: 113 ± 11 vs. 89 ± 11 mmHg, P < 0.05) and lung static compliance (mean ± SD: 0.74 ± 0.07 vs. 0.45 ± 0.07 ml · cm H2O−1, P < 0.05), resolving lung inflammation, and restoring histologic structure compared with vehicle. CD362+ human mesenchymal stromal cells efficacy was at least comparable to heterogenous human mesenchymal stromal cells. Conclusions A CD362+ human mesenchymal stromal cell population decreased Escherichia coli–induced pneumonia severity and enhanced recovery after ventilator-induced lung injury.

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