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. 2019 Feb;104(2):e54-e58.
doi: 10.3324/haematol.2018.196568. Epub 2018 Sep 20.

Bone marrow mesenchymal stem/stromal cells from risk-stratified acute myeloid leukemia patients are anti-inflammatory in in vivo preclinical models of hematopoietic reconstitution and severe colitis

Rafael Diaz de la Guardia  1 , Belen Lopez-Millan  1 , Heleia Roca-Ho  1 , Clara Bueno  1 , Francisco Gutiérrez-Agüera  1 , Jose Luis Fuster  2 , Eduardo Anguita  3 , Samanta Romina Zanetti  1 , Susana Vives  4 , Josep Nomdedeu  5 , Robert Sackstein  6 , Jessie Lavoie  7 , Elena Gónzalez-Rey  8 , Mario Delgado  8 , Michael Rosu-Myles  7 , Pablo Menendez  9   10   11
Affiliations

Bone marrow mesenchymal stem/stromal cells from risk-stratified acute myeloid leukemia patients are anti-inflammatory in in vivo preclinical models of hematopoietic reconstitution and severe colitis

Rafael Diaz de la Guardia et al. Haematologica. 2019 Feb.
No abstract available

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Figures

Figure 1.
Figure 1.
BMSCs from risk-stratified AML patients support in vitro homeostasis of CB-CD34+ HSPCs cells. (A) Schematic depicting the experimental design. (B) In vitro expansion kinetics of CB-CD34+ HSPCs alone (n=9) or co-cultured on BMSCs from HD (n=9) and AML patients (n=27; LR, n=9; IR, n=9; HR, n=9). This “n” is applicable to all subsequent graphs of this figure. (C) Kinetics of loss of CD34 antigen over time in CD34:BMSCs co-cultures. (D) Proportion of cycling CD34+ cells measured at day 11 of CD34:BMSCs co-cultures. (E) Proportion of apoptotic CB-CD34+ cells (Annexin V+) measured at day 11 of CD34:BMSCs co-cultures. (F) The primary clonogenic potential of CB-CD34+ HSPCs previously co-cultured 4 days with HD- or AML-BMSCs. (G) Clonogenic potential of CD34+ progenitors replated in secondary CFC assays normalized against -BMSCs. CFU-Mix (also known as CFU-GEMM) is a Colony-Forming Unit-Granulocyte, Erythrocyte, Monocyte/macrophage, Megakaryocyte. (H) Scoring of primary CFCs. CD34+ cells not previously exposed to BMSCs, were used as base-line control for CD34: BMSCs co-cultures. Because HSPCs gradually lose CD34 expression, we refer to them, we refer to them as “non-adherent cells” rather than “CD34+ cells”. *P< 0.05; ** P<0.01 for CFU-Mix and & P<0.05 for CFU-GM between BMSC groups and -BMSCs.
Figure 2.
Figure 2.
BMSCs from risk-stratified AML patients do not impair in vivo multilineage repopulating function of CB-CD34+ HSPCs. (A) Representative FACS analysis of the graft. The human graft is identified as the CD45+HLA-ABC+ fraction. The CD45+ human graft comprises B-lymphoid cells (CD19+), myeloid cells (CD33+) as well as immature CD34+ and CD34+CD38− cells. (B) Long-term multilineage hematopoietic reconstitution in the IT, CL, PB and spleen of NSG mice sacrificed 6-7 weeks after intra BM injection of CB-CD34+ HSPCs alone (n=5) or co-cultured for 4 days in BMSCs from HD (n=5) or AML patients (n=15; LR, n=5; IR, n=5; HR, n=5). n=90 mice, 4 per donor/patient. (C) Multilineage and multiorgan human chimerism demonstrating that AML-BMSCs do not negatively impact migration of HSPCs from the IT. No differences in the graft composition were found between CD34+ HSPCs co-cultured with BMSCs from HD or risk-stratified AML patients. (D) Long-term BM hematopoietic reconstitution assessed upon serial transplantation of primografted cells. IT: injected tibia; CL: contralateral tibia and femur; PB: peripheral blood.
Figure 3.
Figure 3.
BMSCs from AML patients are highly anti-inflammatory in vivo in an experimental model of acute severe colitis. Colitis was induced by intracolonic administration of TNBS and mice were treated i.p. with PBS (TNBS group), HD-BMSCs or AML-BMSCs (106 cells) 12 hours after TNBS injection. Control mice received 50% ethanol. Clinical evolution was monitored by determining the daily body weight loss (A) as well as measuring the colitis score at day 3 (B), survival (C) the macroscopic colonic damage score (D), and the histopathologic score at day 3 (E). Data are expressed as mean±s.e.m. n=10 mice per group in a-d. n=5 mice per group in e. Statistical differences between groups were calculated as described in the methods section. (F) Serum levels on the indicated cytokines in colitis mice treated with either HD- or AML-BMSCs. (G) Levels of IL6 and IL8 produced by in vitro expanded HD- and AML-BMSCs. *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001.
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References

    1. Grimwade D, Lo Coco F. Acute promyelocytic leukemia: a model for the role of molecular diagnosis and residual disease monitoring in directing treatment approach in acute myeloid leukemia. Leukemia. 2002;16(10):1959–1973. - PubMed
    1. Garcia-Castro J, Trigueros C, Madrenas J, Perez-Simon JA, Rodriguez R, Menendez P. Mesenchymal stem cells and their use as cell replacement therapy and disease modelling tool. J Cell Mol Med. 2008;12(6B):2552–2565. - PMC - PubMed
    1. Brenner AK, Nepstad I, Bruserud O. Mesenchymal stem cells support survival and proliferation of primary human acute myeloid leukemia cells through heterogeneous molecular mechanisms. Front Immunol. 2017;8:106. - PMC - PubMed
    1. Ito S, Barrett AJ, Dutra A, et al. Long term maintenance of myeloid leukemic stem cells cultured with unrelated human mesenchymal stromal cells. Stem Cell Res. 2015;14(1):95–104. - PMC - PubMed
    1. Diaz de la Guardia R, Lopez-Millan B, Lavoie JR, et al. Detailed characterization of mesenchymal stem/stromal cells from a large cohort of AML patients demonstrates a definitive link to treatment outcomes. Stem Cell Reports. 2017;8(6):1573–1586. - PMC - PubMed

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