Mitigating effects of hUCB-MSCs on the hematopoietic syndrome resulting from total body irradiation

Shim, Sehwan; Lee, Seung Bum; Lee, Jong-geol; Jang, Won‐Suk; Lee, Sun-Joo; Park, Sunhoo; Lee, Seung-Sook

doi:10.1016/j.exphem.2013.01.002

Cited by 35 publications

(27 citation statements)

References 46 publications

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“…Recent studies suggested the administration of syngeneic or allogeneic mesenchymal stem cells (MSC) from different syngeneic or allogeneic sources [50], [56]–[58], as well as myeloid precursors [59] to enhance the recovery of damaged BM and for mitigation of radiation effects. The mechanism of action of such treatments and their safety are being questioned.…”

Section: Discussionmentioning

confidence: 99%

Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells

et al. 2013

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Exposure to high lethal dose of ionizing radiation results in acute radiation syndrome with deleterious systemic effects to different organs. A primary target is the highly sensitive bone marrow and the hematopoietic system. In the current study C3H/HeN mice were total body irradiated by 7.7 Gy. Twenty four hrs and 5 days after irradiation 2×106 cells from different preparations of human derived 3D expanded adherent placental stromal cells (PLX) were injected intramuscularly. Treatment with batches consisting of pure maternal cell preparations (PLX-Mat) increased the survival of the irradiated mice from ∼27% to 68% (P<0.001), while cell preparations with a mixture of maternal and fetal derived cells (PLX-RAD) increased the survival to ∼98% (P<0.0001). The dose modifying factor of this treatment for both 50% and 37% survival (DMF50 and DMF37) was∼1.23. Initiation of the more effective treatment with PLX-RAD injection could be delayed for up to 48 hrs after irradiation with similar effect. A delayed treatment by 72 hrs had lower, but still significantly effect (p<0.05). A faster recovery of the BM and improved reconstitution of all blood cell lineages in the PLX-RAD treated mice during the follow-up explains the increased survival of the cells treated irradiated mice. The number of CD45+/SCA1+ hematopoietic progenitor cells within the fast recovering population of nucleated BM cells in the irradiated mice was also elevated in the PLX-RAD treated mice. Our study suggests that IM treatment with PLX-RAD cells may serve as a highly effective “off the shelf” therapy to treat BM failure following total body exposure to high doses of radiation. The results suggest that similar treatments may be beneficial also for clinical conditions associated with severe BM aplasia and pancytopenia.

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Section: Discussionmentioning

confidence: 99%

Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells

et al. 2013

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“…Some studies showed that MSCs can prevent graft-versus-host disease (GVHD) and improve hematopoiesis when coinfused with HSCs [ 20 , 21 ]. Hence, animal models have been developed to assess the response of MSCs in acquired AA as well as the hematologic cell amelioration [ 22 – 24 ] to find conditions to improve HSC transplant regimens or even to evaluate its own effect to reverse BMF and consequently to enhance survival rates of the patients.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell Benefits Observed in Bone Marrow Failure and Acquired Aplastic Anemia

Gonzaga

Wenceslau²,

Lisboa

et al. 2017

Stem Cells International

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Acquired aplastic anemia (AA) is a type of bone marrow failure (BMF) syndrome characterized by partial or total bone marrow (BM) destruction resulting in peripheral blood (PB) pancytopenia, which is the reduction in the number of red blood cells (RBC) and white blood cells (WBC), as well as platelets (PLT). The first-line treatment option of AA is given by hematopoietic stem cell (HSCs) transplant and/or immunosuppressive (IS) drug administration. Some patients did not respond to the treatment and remain pancytopenic following IS drugs. The studies are in progress to test the efficacy of adoptive cellular therapies as mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable allogeneic transplants in refractory severe aplastic anemia (SAA) cases. Moreover, bone marrow stromal cells (BMSC) constitute an essential component of the hematopoietic niche, responsible for stimulating and enhancing the proliferation of HSCs by secreting regulatory molecules and cytokines, providing stimulus to natural BM microenvironment for hematopoiesis. This review summarizes scientific evidences of the hematopoiesis improvements after MSC transplant, observed in acquired AA/BMF animal models as well as in patients with acquired AA. Additionally, we discuss the direct and indirect contribution of MSCs to the pathogenesis of acquired AA.

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“…There is an evidence that MSCs and myeloid cells functionally co-operate, enhancing the activity of natural immune cells in anti-infective protection [46]. The transplantation of human umbilical cord blood MSCs into irradiated rats has greatly contributed to the regeneration of bone marrow [47] and the immune system as a whole [48]. In addition, MSCs show metabolic and adaptogenic activity, which promotes post-stress regeneration of the immune system [49].…”

Section: Resultsmentioning

confidence: 99%

The effects of the transplantation of thymus-derived multipotent stromal cells on the immune system and survival of lethally irradiated mice

Nikolska¹

2018

JCOT

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The traditional source for regeneration of the immune system is hematopoietic stem cells. Multipotent stromal cells (MSCs), especially MSCs of the thymus, have been significantly less studied for this purpose.The aim was to study the regenerative, immunobiological and radioprotective properties of thymus-derived multipotent stromal cells.Materials and methods. Researches were conducted to study the effect of transplantation of thymus-derived MSCs on the survival and features of restoration of the immune system of lethally irradiated mice. Lethally irradiated (with dose 9 Gy) CBA mice, 5-6 weeks old, were injected intravenously with 5·104 thymus-derived MSCs. On the 30th day the cellularity of lymphoid organs, bone marrow and blood, natural and adaptive immunity were studied.Results. It was found that transplanted thymus-derived MSCs significantly prolonged the survival and average lifespan of mice, restored the cellularity of bone marrow, the ability of bone marrow stromal cells to form fibroblast colonies, greatly increased the cellularity of the thymus and contributed to the normalization of the number of leukocytes in the blood. In addition, the natural cytotoxic activity of splenocytes and their ability to synthesize α/β- and γ-interferons, significantly increased, the number of antibody-producing cells was stimulated and the synthesis of antibodies increased. The concentration of the tumor necrosis factor α in the blood was significantly reduced.Conclusions. The results indicate that thymus-derived MSCs possess pronounced regenerative and immunobiological activity, which provides these cells with radioprotective ability. The obtained data can be used to develop combined cell transplants and new methods for improving their regenerative potential and radioprotective effects.

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Mitigating effects of hUCB-MSCs on the hematopoietic syndrome resulting from total body irradiation

Cited by 35 publications

References 46 publications

Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells

Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells

Mesenchymal Stem Cell Benefits Observed in Bone Marrow Failure and Acquired Aplastic Anemia

The effects of the transplantation of thymus-derived multipotent stromal cells on the immune system and survival of lethally irradiated mice

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