Stromal Progenitor Cells in Mitigation of Non-Hematopoietic Radiation Injuries

Overview

Journal Curr Pathobiol Rep

Specialty Pathology

Date 2017 May 3

PMID 28462013

Citations 4

Authors

Shilpa Kulkarni

Timothy C Wang

Chandan Guha

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: Therapeutic exposure to high doses of radiation can severely impair organ function due to ablation of stem cells. Normal tissue injury is a dose-limiting toxicity for radiation therapy (RT). Although advances in the delivery of high precision conformal RT has increased normal tissue sparing, mitigating and therapeutic strategies that could alleviate early and chronic radiation effects are urgently needed in order to deliver curative doses of RT, especially in abdominal, pelvic and thoracic malignancies. Radiation-induced gastrointestinal injury is also a major cause of lethality from accidental or intentional exposure to whole body irradiation in the case of nuclear accidents or terrorism. This review examines the therapeutic options for mitigation of non-hematopoietic radiation injuries.

Recent Findings: We have developed stem cell based therapies for the mitigation of acute radiation syndrome (ARS) and radiation-induced gastrointestinal syndrome (RIGS). This is a promising option because of the robustness of standardized isolation and transplantation of stromal cells protocols, and their ability to support and replace radiation-damaged stem cells and stem cell niche. Stromal progenitor cells (SPC) represent a unique multipotent and heterogeneous cell population with regenerative, immunosuppressive, anti-inflammatory, and wound healing properties. SPC are also known to secrete various key cytokines and growth factors such as platelet derived growth factors (PDGF), keratinocyte growth factor (KGF), R-spondins (Rspo), and may consequently exert their regenerative effects via paracrine function. Additionally, secretory vesicles such as exosomes or microparticles can potentially be a cell-free alternative replacing the cell transplant in some cases.

Summary: This review highlights the beneficial effects of SPC on tissue regeneration with their ability to (a) target the irradiated tissues, (b) recruit host stromal cells, (c) regenerate endothelium and epithelium, (d) and secrete regenerative and immunomodulatory paracrine signals to control inflammation, ulceration, wound healing and fibrosis.

Citing Articles

Gastrointestinal Acute Radiation Syndrome: Mechanisms, Models, Markers, and Medical Countermeasures.

Winters T, Marzella L, Molinar-Inglis O, Price P, Han N, Cohen J Radiat Res. 2024; 201(6):628-646.

PMID: 38616048 PMC: 11658916. DOI: 10.1667/RADE-23-00196.1.

Extracellular Vesicles for the Treatment of Radiation Injuries.

Nanduri L, Duddempudi P, Yang W, Tamarat R, Guha C Front Pharmacol. 2021; 12:662437.

PMID: 34084138 PMC: 8167064. DOI: 10.3389/fphar.2021.662437.

Targets for protection and mitigation of radiation injury.

Khodamoradi E, Hoseini-Ghahfarokhi M, Amini P, Motevaseli E, Shabeeb D, Musa A Cell Mol Life Sci. 2020; 77(16):3129-3159.

PMID: 32072238 PMC: 11104832. DOI: 10.1007/s00018-020-03479-x.

Optimized Xenograft Protocol for Chronic Lymphocytic Leukemia Results in High Engraftment Efficiency for All CLL Subgroups.

Decker S, Zwick A, Saleem S, Kissel S, Rettig A, Aumann K Int J Mol Sci. 2019; 20(24).

PMID: 31842407 PMC: 6940872. DOI: 10.3390/ijms20246277.

References

Fuks Z, Haimovitz-Friedman A, Kolesnick R . The role of the sphingomyelin pathway and protein kinase C in radiation-induced cell kill. Important Adv Oncol. 1995; :19-31. View

Semont A, Mouiseddine M, Francois A, Demarquay C, Mathieu N, Chapel A . Mesenchymal stem cells improve small intestinal integrity through regulation of endogenous epithelial cell homeostasis. Cell Death Differ. 2009; 17(6):952-61. DOI: 10.1038/cdd.2009.187. View

Farrell C, Bready J, Rex K, Chen J, DiPalma C, Whitcomb K . Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality. Cancer Res. 1998; 58(5):933-9. View

Chapel A, Francois S, Douay L, Benderitter M, Voswinkel J . New insights for pelvic radiation disease treatment: Multipotent stromal cell is a promise mainstay treatment for the restoration of abdominopelvic severe chronic damages induced by radiotherapy. World J Stem Cells. 2013; 5(4):106-11. PMC: 3812515. DOI: 10.4252/wjsc.v5.i4.106. View

Sangiorgi E, Capecchi M . Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet. 2008; 40(7):915-20. PMC: 2906135. DOI: 10.1038/ng.165. View

Mason K, Withers H, McBride W, Davis C, Smathers J . Comparison of the gastrointestinal syndrome after total-body or total-abdominal irradiation. Radiat Res. 1989; 117(3):480-8. View

Ranganath S, Levy O, Inamdar M, Karp J . Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell. 2012; 10(3):244-58. PMC: 3294273. DOI: 10.1016/j.stem.2012.02.005. View

Schuller B, Rogers A, Cormier K, Riley K, Binns P, Julius R . No significant endothelial apoptosis in the radiation-induced gastrointestinal syndrome. Int J Radiat Oncol Biol Phys. 2007; 68(1):205-10. DOI: 10.1016/j.ijrobp.2006.12.069. View

Haimovitz-Friedman A, Kan C, Ehleiter D, Persaud R, McLoughlin M, Fuks Z . Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med. 1994; 180(2):525-35. PMC: 2191598. DOI: 10.1084/jem.180.2.525. View

10.

Babb R . Radiation proctitis: a review. Am J Gastroenterol. 1996; 91(7):1309-11. View

11.

Lee J, Fang X, Krasnodembskaya A, Howard J, Matthay M . Concise review: Mesenchymal stem cells for acute lung injury: role of paracrine soluble factors. Stem Cells. 2011; 29(6):913-9. PMC: 3293251. DOI: 10.1002/stem.643. View

12.

Okunieff P, Mester M, Wang J, Maddox T, Gong X, Tang D . In vivo radioprotective effects of angiogenic growth factors on the small bowel of C3H mice. Radiat Res. 1998; 150(2):204-11. View

13.

Wang Y, Chen X, Cao W, Shi Y . Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014; 15(11):1009-16. DOI: 10.1038/ni.3002. View

14.

Barker N, van Es J, Kuipers J, Kujala P, van den Born M, Cozijnsen M . Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007; 449(7165):1003-7. DOI: 10.1038/nature06196. View

15.

Xu W, Chen J, Liu X, Li H, Qi X, Guo X . Autologous bone marrow stromal cell transplantation as a treatment for acute radiation enteritis induced by a moderate dose of radiation in dogs. Transl Res. 2016; 171:38-51. DOI: 10.1016/j.trsl.2015.12.010. View

16.

Tian H, Biehs B, Warming S, Leong K, Rangell L, Klein O . A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature. 2011; 478(7368):255-9. PMC: 4251967. DOI: 10.1038/nature10408. View

17.

Rodriguez M, Martin M, Padellano L, Palomo A, Puebla Y . Gastrointestinal toxicity associated to radiation therapy. Clin Transl Oncol. 2010; 12(8):554-61. DOI: 10.1007/s12094-010-0553-1. View

18.

Chang H, Lin L, Chang P, Luo C, Chang Y, Chou C . Bone marrow transplantation enhances trafficking of host-derived myelomonocytic cells that rescue intestinal mucosa after whole body radiation. Radiother Oncol. 2012; 104(3):401-7. DOI: 10.1016/j.radonc.2011.12.003. View

19.

Semont A, Demarquay C, Bessout R, Durand C, Benderitter M, Mathieu N . Mesenchymal stem cell therapy stimulates endogenous host progenitor cells to improve colonic epithelial regeneration. PLoS One. 2013; 8(7):e70170. PMC: 3726425. DOI: 10.1371/journal.pone.0070170. View

20.

Prasanna P, Stone H, Wong R, Capala J, Bernhard E, Vikram B . Normal tissue protection for improving radiotherapy: Where are the Gaps?. Transl Cancer Res. 2012; 1(1):35-48. PMC: 3411185. View