Low dose-rate irradiation specifically affects hematopoietic stem cells

2016 ◽  
Vol 44 (9) ◽  
pp. S101-S102
Author(s):  
Yoshihiro Takihara ◽  
Yoshinori Ohno ◽  
Kyoko Suzuki-Takedachi ◽  
Mimoko Santo ◽  
Shin’ichiro Yasunaga ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Dose Rate ◽  
Low Dose ◽  
Hematopoietic Stem ◽  
Low Dose Rate

Durable Engraftment of Purified Allogeneic Hematopoietic Stem Cells Following Non-Myeloablative Conditioning.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2204-2204
Author(s):  
Mary-Elizabeth A. Muchmore ◽  
Matthew J. Burge ◽  
Judith A. Shizuru
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Low Dose ◽  
Conditioning Regimen ◽  
Mixed Chimerism ◽  
Host Immune System ◽  
Solid Organ ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Hsc Transplantation

Abstract Transplantation of purified allogeneic hematopoietic stem cells (HSC) has the potential to be a curative treatment for autoimmune diseases. Before it becomes a viable therapy, however, the treatment-related mortality and difficulty of achieving engraftment must be addressed. Our research has focused on developing non-myeloablative regimens that lead to donor-derived engraftment of purified HSC in a murine model. Total lymphoid irradiation (TLI) consists of low-dose fractionated irradiation targeted to the thymus, abdomen, and peripheral nodes, while the skull, lungs, and long bones remain shielded. The non-myeloablative conditioning regimen of TLI and anti-thymocyte globulin (ATG) was followed by HSC transplantation. HSCs were isolated by the composite phenotype of Thy1.1+, c-kit+, Sca-1+, and lineage- (KTLS) or, in strains lacking the Thy1.1 marker, c-kit+, Sca-1+, and lineage- (KSL). We tested HSC transplantations across three major histocompatiblity complex (MHC)-matched strain combinations known through previous studies in our group to have significantly different barriers to engraftment. In all three strain combinations we observed stable mixed chimerism (approximately 50% donor-derived cells) when high doses of HSC (10,000/mouse) were administered. Chimerism was measured at thirty-day intervals, and initially sharply increased and then stabilized around day ninety post-transplantation. In prior studies from our laboratory in a spontaneously arising autoimmune diabetes model, we demonstrated that mixed allogeneic chimerism alone following low dose total body irradiation (TBI) and HSC transplantation was sufficient to block the autoimmune pathogenesis. In order to establish a second clinically relevant conditioning regimen, we attempted here to lower the dose of TBI by using cyclophosphamide and ATG in addition to low dose TBI. However, less robust engraftment was observed as compared to the TLI/ATG approach. To study how TLI/ATG allows engraftment, we have examined the marrow of TLI/ATG conditioned, untransplanted animals. Though TUNEL and Caspase-3 assays did not show a significant increase in apoptosis compared to controls, a 71% decrease in the quantitative number of HSCs isolated from these animals was observed. This depletion of HSCs in the marrow could provide a niche for donor HSCs to inhabit. Further histologic studies on lymphoid organs exposed to radiation through TLI, including the thymus and spleen, are ongoing and may further elucidate the mechanisms by which TLI reconditions the host immune system. The durable mixed chimerism observed following TLI/ATG conditioning and HCT will be applied to mice affected with the rodent form of multiple sclerosis (experimental autoimmune encephalomyelitis) and to tolerance induction of solid-organ grafts. SUMMARY: The combination of TLI/ATG non-myeloablative conditioning and transplantation of allogeneic HSC leads to a durable mixed chimeric state between donor and host and will next be applied to the induction of tolerance to autoantigens and alloantigens.

Plasmacytoid Dendritic Cells Derived from Chronic Myeloid Leukemia Induced by Low Dose Cytosine Arabinoside Combined with Flt-3L and TPO

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4918-4918
Author(s):  
Lijuan Li ◽  
Lian- Sheng Zhang
Keyword(s):  
Stem Cells ◽  
Dendritic Cells ◽  
Chronic Myeloid Leukemia ◽  
Influenza Vaccine ◽  
Hematopoietic Stem Cells ◽  
Cytosine Arabinoside ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Control Group ◽  
Hematopoietic Stem

Abstract Objective Plasmacytoid dendritic cells(pDC) as a subtype of dendritic cells, play an important immunological effects in the body.It is a focus in resent research. After stimulated by viruses or CpG ODNs, pDC produce large amounts of IFN-α rapidly, result in an strong non-specific immunological effect, and then become differentiation and maturation, and attained certain antigen presenting function in adaptive immune response, act as a bridge connecting innate immunity with adaptive immunity. In vitro, FLT-3L combination with TPO can successfully develop pDC from hematopoietic stem cells. Chronic myeloid leukemia(CML) is a hematopoietic stem cell malignant proliferation of the disease. There are series of immune abnormalities in patients with CML. It is well known that Interferon - α treatment of CML is effective, patients can be gained part of cytogenetic and molecular biology mitigation, and effective in patients with interferon therapy, the long-term prognosis is superior to other methods of treatment. Clinical experience also found that low dose cytosine arabinoside(LD-Ara-C) in combination with interferon is superior therapeutic effect of interferon treatment alone. We assumed that whether the LD-Ara-C in patients has an improvement in the immune dysfunction? Whether it will affect on CML-derived pDC differentiation, maturation and function? Therefore, we used LD-Ara-C joint FLT-3L, TPO cultivante CML-derived hematopoietic stem cells that make it differentiate into CML derived pDC to study LD-Ara-C for the treatment of CML may be immune mechanism for the clinical treatment theory. Method Bone marrow mononuclear cells (BMMNCs) were isolated from CML patients in chronic phase at diagnosis by density gradient centrifugation. BMMNCs were incubate with a cocktail of Flt-3 and TPO, Ara-C were added at the same time of 5ng/ml (A1), 10ng/ml (A2), 25ng/ml (A3), 50ng/ml (A4) and zero as the control, respectively. After 30 days of culture, the morphologic features were observed and CD4,CD11c, CD123, BDCA-2 were analyzed by flow cytometry, IFN-α concentration in supernate were detected by ELISA kits after added influenza vaccine. Results after 25d of culture, cells clustered with increased size and widespread cytoplasmic projection. Wright-Giemsa-stained cytospin preparation the pDC displays an eccentric kidney-shaped nucleus.The immunophenotype expression of CD4,CD123 and BDCA-2 on pDCs of group A1 and A2 were obviously higher than control group(p<0.05),and group A1 were higher than A2(p<0.05). The majority cells of group A3 and all cells of A4 were died. The group A1 had the highest level of the secretion of IFN-α than A2 and than control group(p<0.05) Conclusion LD-Ara-C in combination with Flt-3 and TPO can induce CML cells into pDCs which express the typical immunophenotype, Increase the production of IFN-α on stimulated by influenza vaccine. This study indicates that LD-Ara-C increase the quantity of pDC and IFN-α production, and this maybe explain why the therapy with LD-Ara-C in CML patients have better outcome.

Ultra low-dose IL-2 mediated expansion of regulatory T cells as GvHD prophylaxis for recipients of allogeneic hematopoietic stem cells

Cytotherapy ◽  
2013 ◽  
Vol 15 (4) ◽  
pp. S41-S42
Author(s):  
S. Ku ◽  
A.A. Kennedy-Nasser ◽  
Y. Hazrat ◽  
J. Melenhorst ◽  
A. Barrett ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Regulatory T Cells ◽  
Hematopoietic Stem Cells ◽  
Low Dose ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis

scholarly journals Cellular responses and gene expression profiles of colonic Lgr5+ stem cells after low-dose/low-dose-rate radiation exposure

2017 ◽  
Vol 59 (suppl_2) ◽  
pp. ii18-ii22 ◽  
Author(s):  
Kensuke Otsuka ◽  
Keiji Suzuki ◽  
Yuki Fujimichi ◽  
Masanori Tomita ◽  
Toshiyasu Iwasaki
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Radiation Exposure ◽  
Dose Rate ◽  
Low Dose ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cellular Responses ◽  
Low Dose Rate

scholarly journals Low-dose parenteral busulfan provides an extended window for the infusion of hematopoietic stem cells in murine hosts

2007 ◽  
Vol 35 (9) ◽  
pp. 1415-1420 ◽  
Author(s):  
Matthew M. Hsieh ◽  
Saskia Langemeijer ◽  
Aisha Wynter ◽  
Oswald A. Phang ◽  
Elizabeth M. Kang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Low Dose ◽  
Hematopoietic Stem

scholarly journals Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells

Cell Reports ◽  
2017 ◽  
Vol 20 (13) ◽  
pp. 3199-3211 ◽  
Author(s):  
Sarah Rodrigues-Moreira ◽  
Stéphanie G. Moreno ◽  
Giulia Ghinatti ◽  
Daniel Lewandowski ◽  
Françoise Hoffschir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Low Dose ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Dose Irradiation
Sign in / Sign up

Export Citation Format

Share Document