scholarly journals Macrophages Educated with Exosomes from Primed Mesenchymal Stem Cells Treat Acute Radiation Syndrome by Promoting Hematopoietic Recovery

2019 ◽  
Vol 25 (11) ◽  
pp. 2124-2133 ◽  
Author(s):  
John A. Kink ◽  
Matthew H. Forsberg ◽  
Sofiya Reshetylo ◽  
Soroush Besharat ◽  
Charlie J. Childs ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Acute Radiation ◽  
Acute Radiation Syndrome ◽  
Hematopoietic Recovery

scholarly journals The healing effect of bone marrow-derived stem cells in acute radiation syndrome

2016 ◽  
Vol 32 (3) ◽  
Author(s):  
Seyed Mohammad Javad Mortazavi ◽  
Fatemeh Shekoohi-Shooli ◽  
Seyed Mahmood Reza Aghamir ◽  
Davood Mehrabani ◽  
Amirreza Dehghanian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Radiation ◽  
Acute Radiation Syndrome ◽  
Healing Effect

Chemokines and Cytokines Required for Migration of Mesechymal Stem Cells into Marrow or Injured Tissues.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4268-4268
Author(s):  
Tatiana Tondreau ◽  
Meuleman Nathalie ◽  
Delforge Alain ◽  
Dejeneffe Marielle ◽  
Massy Martine ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cotton Swab ◽  
Matrigel Invasion ◽  
Hematopoietic Recovery ◽  
Cxcr4 Receptor ◽  
Spontaneous Migration ◽  
Bottom Chamber ◽  
Upper Chamber

Abstract Background: Intravenous infusion of mesenchymal stem cells (MSC) after chemotherapy are currently used to accelerate the hematopoietic recovery but their potential of migration and homing to bone marrow is poorly understood. Methods: Bone marrow MSC (BM-MSC) were isolated with the classical plastic adhesion method. Cultured MSC were identified through their expression of SH2, SH3, CD44, CD105 but lacked typical hematopoietic antigens: CD14, CD31, CD34, CD45 and CD62-e. The MSC migration was evaluated using matrigel invasion chamber assay. MSC were used at 5.105 cells/mL in the upper chamber. In the bottom chamber, different cytokines were tested for their chemoattractive properties: SDF-1 (100ng/mL), PDGF-bb (100ng/mL), IGF (0,5 μg/mL) and IL-6 (100ng/mL) in a serum free medium. BM-MSC conditionned medium (CM) at 10% was also used as chemoattractant. After 24 hours, cells that had not migrated were removed from the top of the insert by scrubbing with a cotton swab and cells that migrated through the membrane were counted after staining with 0,5% crystal violet. Results: We observed that MSC migration was greater in the presence of PDGF-bb, IL-6 or with 10% CM with respectively an increase of 6,6; 5,6 and 5 fold compared to spontaneous migration. Only a small number of MSC migrated in response to SDF-1, and this observation correlates with the very low expression of CXCR4 receptor (0,67±0,08%). Indeed, we demonstrated that CXCR4, the SDF-1 receptor was mainly intracytoplasmic expressed (74,9±1,3%). Conclusions: IL-6 and PDGF-bb are important cytokines produced by the bone marrow microenvironment or by injured tissues. In our study, we thus demonstrated that these chmokines could be involved in the migration of MSC to bone marrow as well as to damaged tissues. Mesenchymal stem cells migration Ctrl SDF-1 IGF-1 10%CM IL-6 PDGF-bb *number of cells evaluated/3 fields of view. Migrated MSC * 13,7±2,7 24,9±5 42,2±12,6 69±17,9 77,1±14,1 90,5±5,3

Rapid Hematopoietic Recovery After Coinfusion of Autologous-Blood Stem Cells and Culture-Expanded Marrow Mesenchymal Stem Cells in Advanced Breast Cancer Patients Receiving High-Dose Chemotherapy

2000 ◽  
Vol 18 (2) ◽  
pp. 307-307 ◽  
Author(s):  
Omer N. Koç ◽  
Stanton L. Gerson ◽  
Brenda W. Cooper ◽  
Stephanie M. Dyhouse ◽  
Stephen E. Haynesworth ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cancer Patients ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Human Mscs ◽  
Breast Cancer Patients ◽  
Hematopoietic Recovery

PURPOSE: Multipotential mesenchymal stem cells (MSCs) are found in human bone marrow and are shown to secrete hematopoietic cytokines and support hematopoietic progenitors in vitro. We hypothesized that infusion of autologous MSCs after myeloablative therapy would facilitate engraftment by hematopoietic stem cells, and we investigated the feasibility, safety, and hematopoietic effects of culture-expanded MSCs in breast cancer patients receiving autologous peripheral-blood progenitor-cell (PBPC) infusion. PATIENTS AND METHODS: We developed an efficient method of isolating and culture-expanding a homogenous population of MSCs from a small marrow-aspirate sample obtained from 32 breast cancer patients. Twenty-eight patients were given high-dose chemotherapy and autologous PBPCs plus culture-expanded MSC infusion and daily granulocyte colony-stimulating factor. RESULTS: Human MSCs were successfully isolated from a mean ± SD of 23.4 ± 5.9 mL of bone marrow aspirate from all patients. Expansion cultures generated greater than 1 × 106 MSCs/kg for all patients over 20 to 50 days with a mean potential of 5.6 to 36.3 × 106 MSCs/kg after two to six passages, respectively. Twenty-eight patients were infused with 1 to 2.2 × 106 expanded autologous MSCs/kg intravenously over 15 minutes. There were no toxicities related to the infusion of MSCs. Clonogenic MSCs were detected in venous blood up to 1 hour after infusion in 13 of 21 patients (62%). Median time to achieve a neutrophil count greater than 500/μL and platelet count ≥ 20,000/μL untransfused was 8 days (range, 6 to 11 days) and 8.5 days (range, 4 to 19 days), respectively. CONCLUSION: This report is the first describing infusion of autologous MSCs with therapeutic intent. We found that autologous MSC infusion at the time of PBPC transplantation is feasible and safe. The observed rapid hematopoietic recovery suggests that MSC infusion after myeloablative therapy may have a positive impact on hematopoiesis and should be tested in randomized trials.

scholarly journals Hematopoietic Stem Cells and Mesenchymal Stromal Cells in Acute Radiation Syndrome

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Liren Qian ◽  
Jian Cen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cellular Therapy ◽  
Acute Radiation ◽  
Hematopoietic Stem ◽  
Acute Radiation Syndrome ◽  
Stem Cell Banks

With the extensive utilization of radioactive materials for medical, industrial, agricultural, military, and research purposes, medical researchers are trying to identify new methods to treat acute radiation syndrome (ARS). Radiation may cause injury to different tissues and organs, but no single drug has been proven to be effective in all circumstances. Radioprotective agents are always effective if given before irradiation, but many nuclear accidents are unpredictable. Medical countermeasures that can be beneficial to different organ and tissue injuries caused by radiation are urgently needed. Cellular therapy, especially stem cell therapy, has been a promising approach in ARS. Hematopoietic stem cells (HSCs) and mesenchymal stromal cells (MSCs) are the two main kinds of stem cells which show good efficacy in ARS and have attracted great attention from researchers. There are also some limitations that need to be investigated in future studies. In recent years, there are also some novel methods of stem cells that could possibly be applied on ARS, like “drug” stem cell banks obtained from clinical grade human induced pluripotent stem cells (hiPSCs), MSC-derived products, and infusion of HSCs without preconditioning treatment, which make us confident in the future treatment of ARS. This review focuses on major scientific and clinical advances of hematopoietic stem cells and mesenchymal stromal cells on ARS.

scholarly journals Exosomes from primed MSCs can educate monocytes as a cellular therapy for hematopoietic acute radiation syndrome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Matthew H. Forsberg ◽  
John A. Kink ◽  
Anna S. Thickens ◽  
Bryson M. Lewis ◽  
Charlie J. Childs ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Radiation ◽  
Prolonged Survival ◽  
Human Monocytes ◽  
Acute Radiation Syndrome ◽  
Nsg Mice ◽  
Human Cd34 ◽  
Hematopoietic Recovery ◽  
Lethal Irradiation

Abstract Background Acute radiation syndrome (ARS) is caused by acute exposure to ionizing radiation that damages multiple organ systems but especially the bone marrow (BM). We have previously shown that human macrophages educated with exosomes from human BM-derived mesenchymal stromal cells (MSCs) primed with lipopolysaccharide (LPS) prolonged survival in a xenogeneic lethal ARS model. The purpose of this study was to determine if exosomes from LPS-primed MSCs could directly educate human monocytes (LPS-EEMos) for the treatment of ARS. Methods Human monocytes were educated by exosomes from LPS-primed MSCs and compared to monocytes educated by unprimed MSCs (EEMos) and uneducated monocytes to assess survival and clinical improvement in a xenogeneic mouse model of ARS. Changes in surface molecule expression of exosomes and monocytes after education were determined by flow cytometry, while gene expression was determined by qPCR. Irradiated human CD34+ hematopoietic stem cells (HSCs) were co-cultured with LPS-EEMos, EEMos, or uneducated monocytes to assess effects on HSC survival and proliferation. Results LPS priming of MSCs led to the production of exosomes with increased expression of CD9, CD29, CD44, CD146, and MCSP. LPS-EEMos showed increases in gene expression of IL-6, IL-10, IL-15, IDO, and FGF-2 as compared to EEMos generated from unprimed MSCs. Generation of LPS-EEMos induced a lower percentage of CD14+ monocyte subsets that were CD16+, CD73+, CD86+, or CD206+ but a higher percentage of PD-L1+ cells. LPS-EEMos infused 4 h after lethal irradiation significantly prolonged survival, reducing clinical scores and weight loss as compared to controls. Complete blood counts from LPS-EEMo-treated mice showed enhanced hematopoietic recovery post-nadir. IL-6 receptor blockade completely abrogated the radioprotective survival benefit of LPS-EEMos in vivo in female NSG mice, but only loss of hematopoietic recovery was noted in male NSG mice. PD-1 blockade had no effect on survival. Furthermore, LPS-EEMos also showed benefits in vivo when administered 24 h, but not 48 h, after lethal irradiation. Co-culture of unprimed EEMos or LPS-EEMos with irradiated human CD34+ HSCs led to increased CD34+ proliferation and survival, suggesting hematopoietic recovery may be seen clinically. Conclusion LPS-EEMos are a potential counter-measure for hematopoietic ARS, with a reduced biomanufacturing time that facilitates hematopoiesis.

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