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Mouse bone marrow-derived mesenchymal stem cells inhibit leukemia/lymphoma cell proliferation in vitro and in a mouse model of allogeneic bone marrow transplant.

Song N, Gao L, Qiu H, Huang C, Cheng H, Zhou H, Lv S, Chen L, Wang J - Int. J. Mol. Med. (2015)

Bottom Line: Cell proliferation, apoptosis, cell cycle progression and the amount of cytokine secretion were then measured using a Cell Counting kit‑8, Annexin V/propidium iodide staining, flow cytometry and ELISA, respectively.Our results revealed that the MSCs inhibited the proliferation of the mouse lymphoma and leukemia cells in vitro, leading to cell cycle arrest and reducing the secretion of interleukin (IL)‑10.The results from the present study indicate that MSCs may be safe and effective when used in allogeneic BMT for the treatment of hemotological malignancies.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Institute of Hematology, PLA, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.

ABSTRACT
The allogeneic hematopoietic stem cell (HSC) transplantation of mesenchymal stem cells (MSCs) contributes to the reconstitution of hematopoiesis by ameliorating acute graft‑versus‑host disease (aGVHD). However, the role of MSCs in graft‑versus‑leukemia remains to be determined. In the present study, we co‑cultured C57BL/6 mouse bone marrow (BM)‑derived MSCs with A20 murine B lymphoma, FBL3 murine erythroleukemia and P388 murine acute lymphocytic leukemia cells. Cell proliferation, apoptosis, cell cycle progression and the amount of cytokine secretion were then measured using a Cell Counting kit‑8, Annexin V/propidium iodide staining, flow cytometry and ELISA, respectively. We also established a model of allogeneic bone marrow transplantation (BMT) using BALB/c mice. Following the administration of A20 cells and MSCs, we recorded the symptoms and the survival of the mice for 4 weeks, assessed the T cell subsets present in peripheral blood, and, after the mice were sacrifice, we determined the infiltration of MSCs into the organs by histological staining. Our results revealed that the MSCs inhibited the proliferation of the mouse lymphoma and leukemia cells in vitro, leading to cell cycle arrest and reducing the secretion of interleukin (IL)‑10. In our model of allogeneic BMT, the intravenous injection of MSCs into the mice injected wth A20 cells decreased the incidence of lymphoma, improved survival, increased the fraction of CD3+CD8+ T cells, decreased the fraction of CD3+CD4+ T cells and CD4+CD25+ T cells in peripheral blood, and ameliorated the manifestation of aGVHD. The results from the present study indicate that MSCs may be safe and effective when used in allogeneic BMT for the treatment of hemotological malignancies.

No MeSH data available.


Related in: MedlinePlus

Cyosections of tissues at (A-D) 24 h or (E-H) 7 days after transplantation. We observed no mesenchymal stem cella (MSCa) in the (A) small intestine and (B) lunga, but numerous PKH26-labeled MSCs in the (C) spleen and (D) kidneya at 24 h post-grafting; (E-H) Fluorescence microscopic images confirmed the presence of PKH26-labeled MSCa in the (E) liver, (F) lunga, (G) spleen and (H) kidneya 7 days after transplantation, and a large number of PKH26-labeled MSCs in the spleen.
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f7-ijmm-36-01-0139: Cyosections of tissues at (A-D) 24 h or (E-H) 7 days after transplantation. We observed no mesenchymal stem cella (MSCa) in the (A) small intestine and (B) lunga, but numerous PKH26-labeled MSCs in the (C) spleen and (D) kidneya at 24 h post-grafting; (E-H) Fluorescence microscopic images confirmed the presence of PKH26-labeled MSCa in the (E) liver, (F) lunga, (G) spleen and (H) kidneya 7 days after transplantation, and a large number of PKH26-labeled MSCs in the spleen.

Mentions: Twenty-four-hours post-grafting, the labeled MSCs were observed to be diffusely distributed in the spleen and kidneys (Fig. 7C and D), while no MSCs were observed in the heart, liver, small intestine (Fig. 7A) or lungs (Fig. 7B). On day 7, we could still observe numerous MSCs within the spleen and kidneys (Fig. 7G and H), which appeared to maintain the elongated, fibroblast-like appearance that they adopt in culture. Furthermore, on day 7, the donor MSCs were present in the liver and lungs of the grafted mice. This indicated that following their infusion, the MSCs mainly migrated to the tumor sites (spleen and liver) and the damaged tissues (lungs and kidneys). We were, however, surprised not to find any MSCs in the easily injured small intestine 24 h or 7 days post-grafting.


Mouse bone marrow-derived mesenchymal stem cells inhibit leukemia/lymphoma cell proliferation in vitro and in a mouse model of allogeneic bone marrow transplant.

Song N, Gao L, Qiu H, Huang C, Cheng H, Zhou H, Lv S, Chen L, Wang J - Int. J. Mol. Med. (2015)

Cyosections of tissues at (A-D) 24 h or (E-H) 7 days after transplantation. We observed no mesenchymal stem cella (MSCa) in the (A) small intestine and (B) lunga, but numerous PKH26-labeled MSCs in the (C) spleen and (D) kidneya at 24 h post-grafting; (E-H) Fluorescence microscopic images confirmed the presence of PKH26-labeled MSCa in the (E) liver, (F) lunga, (G) spleen and (H) kidneya 7 days after transplantation, and a large number of PKH26-labeled MSCs in the spleen.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494598&req=5

f7-ijmm-36-01-0139: Cyosections of tissues at (A-D) 24 h or (E-H) 7 days after transplantation. We observed no mesenchymal stem cella (MSCa) in the (A) small intestine and (B) lunga, but numerous PKH26-labeled MSCs in the (C) spleen and (D) kidneya at 24 h post-grafting; (E-H) Fluorescence microscopic images confirmed the presence of PKH26-labeled MSCa in the (E) liver, (F) lunga, (G) spleen and (H) kidneya 7 days after transplantation, and a large number of PKH26-labeled MSCs in the spleen.
Mentions: Twenty-four-hours post-grafting, the labeled MSCs were observed to be diffusely distributed in the spleen and kidneys (Fig. 7C and D), while no MSCs were observed in the heart, liver, small intestine (Fig. 7A) or lungs (Fig. 7B). On day 7, we could still observe numerous MSCs within the spleen and kidneys (Fig. 7G and H), which appeared to maintain the elongated, fibroblast-like appearance that they adopt in culture. Furthermore, on day 7, the donor MSCs were present in the liver and lungs of the grafted mice. This indicated that following their infusion, the MSCs mainly migrated to the tumor sites (spleen and liver) and the damaged tissues (lungs and kidneys). We were, however, surprised not to find any MSCs in the easily injured small intestine 24 h or 7 days post-grafting.

Bottom Line: Cell proliferation, apoptosis, cell cycle progression and the amount of cytokine secretion were then measured using a Cell Counting kit‑8, Annexin V/propidium iodide staining, flow cytometry and ELISA, respectively.Our results revealed that the MSCs inhibited the proliferation of the mouse lymphoma and leukemia cells in vitro, leading to cell cycle arrest and reducing the secretion of interleukin (IL)‑10.The results from the present study indicate that MSCs may be safe and effective when used in allogeneic BMT for the treatment of hemotological malignancies.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Institute of Hematology, PLA, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.

ABSTRACT
The allogeneic hematopoietic stem cell (HSC) transplantation of mesenchymal stem cells (MSCs) contributes to the reconstitution of hematopoiesis by ameliorating acute graft‑versus‑host disease (aGVHD). However, the role of MSCs in graft‑versus‑leukemia remains to be determined. In the present study, we co‑cultured C57BL/6 mouse bone marrow (BM)‑derived MSCs with A20 murine B lymphoma, FBL3 murine erythroleukemia and P388 murine acute lymphocytic leukemia cells. Cell proliferation, apoptosis, cell cycle progression and the amount of cytokine secretion were then measured using a Cell Counting kit‑8, Annexin V/propidium iodide staining, flow cytometry and ELISA, respectively. We also established a model of allogeneic bone marrow transplantation (BMT) using BALB/c mice. Following the administration of A20 cells and MSCs, we recorded the symptoms and the survival of the mice for 4 weeks, assessed the T cell subsets present in peripheral blood, and, after the mice were sacrifice, we determined the infiltration of MSCs into the organs by histological staining. Our results revealed that the MSCs inhibited the proliferation of the mouse lymphoma and leukemia cells in vitro, leading to cell cycle arrest and reducing the secretion of interleukin (IL)‑10. In our model of allogeneic BMT, the intravenous injection of MSCs into the mice injected wth A20 cells decreased the incidence of lymphoma, improved survival, increased the fraction of CD3+CD8+ T cells, decreased the fraction of CD3+CD4+ T cells and CD4+CD25+ T cells in peripheral blood, and ameliorated the manifestation of aGVHD. The results from the present study indicate that MSCs may be safe and effective when used in allogeneic BMT for the treatment of hemotological malignancies.

No MeSH data available.


Related in: MedlinePlus