Inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media

Author(s): Valencic E, Loganes C, Cesana S, Piscianz E, Gaipa G, et al.

Abstract

Introduction: Despite having a proven immunosuppressive potential in vitro, human mesenchymal stromal cells (MSCs) are reported to display variable efficacy in vivo and, in fact, their proven benefit in the clinical practice is still limited and controversial.

Methods: The interplay between clinical grade MSCs and pre-activated donor lymphocytes or selected lymphocyte subsets was studied in vitro. The kinetics of MSC growth and viability was evaluated by adhesion-dependent changes of culture plate impedance and biochemically by a colorimetric assay. Activation of natural killer (NK) cells was assessed as well, using a flow cytometry assay.

Results: A strong inhibition of MSC growth was rapidly induced by the addition of pre-activated lymphocytes but not of resting lymphocytes. Inhibition seems not to be attributable to a single cell population, as similar results can be obtained by depleting NK cells or by using either selected CD4+ or CD8+ lymphocytes. In addition, conditioned medium (CM) from activated lymphocytes was able to inhibit MSC growth in a dose-dependent manner. Furthermore, licensing with IFN-γ partially protected MSCs from pre-activated lymphocytes but not from their CM. These results suggest an inhibitory role of lymphocyte-activation-derived substances. However, the identification of a single molecule responsible for MSC inhibition remained elusive, even if preliminary experiments showed that ATP and, to a lesser extent, TNF-α might play a role.

Conclusions: These results suggest that survival of MSCs can be affected by soluble mediators released by activated lymphocytes. Thus it can be hypothesized that MSC immunosuppressive action in vivo could be impaired by ongoing immune activation through the release of inflammatory mediators.

Similar Articles

Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis

Author(s): Riordan NH, Ichim TE, Min WP, Wang H, Solano F, et al.

Isolation and characterization of multi-potent stem cells from human orbital fat tissues

Author(s): Ho JH, Ma WH, Tseng TC, Chen YF, Chen MH, et al.

Isolation and characterization of canine adipose-derived mesenchymal stem cells

Author(s): Neupane M, Chang CC, Kiupel M,Yuzbasiyan-Gurkan V

Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives

Author(s): Planat-Benard V, Silvestre JS, Cousin B, Andre M, Nibbelink M, et al.

Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications

Author(s): Yoshimura K, Asano Y, Aoi N, Kurita M, Oshima Y, et al.

Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report

Author(s): Lendeckel S, Jodicke A, Christophis P, Heidinger K, Wolff J, et al.

Adipose-derived stromal cells: Their identity and uses in clinical trials, an update

Author(s): Casteilla L, Planat-Benard V, Laharrague P,Cousin B

A simple modification of the separation method reduces heterogeneity of adipose-derived stem cells

Author(s): Griesche N, Luttmann W, Luttmann A, Stammermann T, Geiger H, et al.

Characterization of adipose tissue-derived cells isolated with the Celution system

Author(s): Lin K, Matsubara Y, Masuda Y, Togashi K, Ohno T, et al.

Sera of overweight people promote in vitro adipocyte differentiation of bone marrow stromal cells

Author(s): Di Bernardo G, Messina G, Capasso S, Del Gaudio S, Cipollaro M, et al.

Comparison of ex vivo expansion culture conditions of mesenchymal stem cells for human cell therapy

Author(s): Perez-Ilzarbe M, Diez-Campelo M, Aranda P, Tabera S, Lopez T, et al.

Ex vivo expansion of human mesenchymal stem cells in defined serum-free media

Author(s): Jung S, Panchalingam KM, Rosenberg L,Behie LA

Optimizing proliferation and characterization of multipotent stem cells from porcine adipose tissue

Author(s): Wang KH, Kao AP, Wangchen H, Wang FY, Chang CH, et al.

Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke

Author(s): Honmou O, Houkin K, Matsunaga T, Niitsu Y, Ishiai S, et al.

Expectations and strategies regarding islet transplantation: metabolic data from the GRAGIL 2 trial

Author(s): Badet L, Benhamou PY, Wojtusciszyn A, Baertschiger R, Milliat-Guittard L, et al.

Human CD34/CD90 ASCs are capable of growing as sphere clusters, producing high levels of VEGF and forming capillaries

Author(s): De Francesco F, Tirino V, Desiderio V, Ferraro G, D'Andrea F, et al.