PreImplantation factor (PIF) therapy provides comprehensive protection against radiation induced pathologies.

Shainer, Reut; Almogi-Hazan, Osnat; Berger, Arye; Hinden, Liad; Müller, Martin; Brodie, Chaya; Simillion, Cedric; Paidas, Michael; Barnea, Eytan R; Or, Reuven (2016). PreImplantation factor (PIF) therapy provides comprehensive protection against radiation induced pathologies. OncoTarget, 7(37), pp. 58975-58994. Impact Journals LLC 10.18632/oncotarget.10635

[img]
Preview
Text
27449294_10635-161790-4-PB.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (4MB) | Preview

Acute Radiation Syndrome (ARS) may lead to cancer and death and has few effective countermeasures. Efficacy of synthetic PIF treatment was demonstrated in preclinical autoimmune and transplantation models. PIF protected against inflammation and mortality following lethal irradiation in allogeneic bone marrow transplant (BMT) model. Herein, we demonstrate that PIF imparts comprehensive local and systemic protection against lethal and sub-lethal ARS in murine models. PIF treatment 2 h after lethal irradiation led to 100% survival and global hematopoietic recovery at 2 weeks after therapy. At 24 h after irradiation PIF restored hematopoiesis in a semi-allogeneic BMT model. PIF-preconditioning provided improved long-term engraftment. The direct effect of PIF on bone marrow cells was also demonstrated in vitro: PIF promoted pre-B cell differentiation and increased immunoregulatory properties of BM-derived mesenchymal stromal cells. PIF treatment also improved hematopoietic recovery and reduced systemic inflammatory cytokine production after sub-lethal radiation exposure. Here, PIF also prevented colonic crypt and basal membrane damage coupled with reduced nitric oxide synthetase (iNOS) and increased (B7h1) expression. Global upper GI gene pathway analysis revealed PIF's involvement in protein-RNA interactions, mitochondrial oxidative pathways, and responses to cellular stress. Some effects may be attributed to PIF's influence on macrophage differentiation and function. PIF demonstrated a regulatory effect on irradiated macrophages and on classically activated M1 macrophages, reducing inflammatory gene expression (iNOS, Cox2), promoting protective (Arg1) gene expression and inducing pro-tolerance cytokine secretion. Notably, synthetic PIF is stable for long-term field use. Overall, clinical investigation of PIF for comprehensive ARS protection is warranted.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology

UniBE Contributor:

Müller, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1949-2553

Publisher:

Impact Journals LLC

Language:

English

Submitter:

Monika Zehr

Date Deposited:

26 Apr 2017 10:08

Last Modified:

26 Apr 2017 10:08

Publisher DOI:

10.18632/oncotarget.10635

PubMed ID:

27449294

Uncontrolled Keywords:

ARS; PreImplantation Factor (PIF); local and systemic protection; oxidative stress

BORIS DOI:

10.7892/boris.94202

URI:

https://boris.unibe.ch/id/eprint/94202

Actions (login required)

Edit item Edit item
Provide Feedback