Use of MSCs and MSC-educated Macrophages to Mitigate Hematopoietic Acute Radiation Syndrome

Overview

Journal Curr Stem Cell Rep

Date 2020 Sep 18

PMID 32944493

Citations 5

Authors

Raghavan Chinnadurai

Matthew H Forsberg

John A Kink

Peiman Hematti

Christian M Capitini

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: Innovative and minimally toxic treatment approaches are sorely needed for the prevention and treatment of hematopoietic acute radiation syndrome (H-ARS). Cell therapies have been increasingly studied for their potential use as countermeasures for accidental and intentional ionizing radiation exposures which can lead to fatal ARS. Mesenchymal stem/stromal cells (MSCs) are a cell therapy that have shown promising results in preclinical studies of ARS, and are being developed in clinical trials specifically for H-ARS. MSCs, MSC-educated macrophages (MEMs) and MSC-exosome educated macrophages (EEMs) all have the potential to be used as adoptive cell therapies for H-ARS. Here we review how MSCs have been reported to mitigate inflammation from radiation injury while also stimulating hematopoiesis during ARS.

Recent Findings: We discuss emerging work with immune cell subsets educated by MSCs, including MEMs and EEMs, in promoting hematopoiesis in xenogeneic models of ARS. We also discuss the first placental-derived MSC product to enter phase I trials, PLX-R18, and the challenges faced by bringing MSC and other cell therapies into the clinic for treating ARS.

Summary: Although MSCs, MEMs and EEMs are potential cell therapy candidates in promoting hematopoietic HRS, challenges persist in translational clinical development of these products to the clinic. Whether any of these cellular therapies will be sufficient as stand-alone therapies to mitigate H-ARS or if they will be a bridging therapy that insures survival until a curative allogeneic hematopoietic stem cell transplant can be performed are the key questions that will have to be answered.

Citing Articles

Interleukin-12 sustained release system promotes hematopoietic recovery after radiation injury.

Lin C, Xiang Y, Zhang Y, Yang Z, Chen N, Zhang W MedComm (2020). 2024; 5(9):e704.

PMID: 39268354 PMC: 11391269. DOI: 10.1002/mco2.704.

Applications of mesenchymal stem cell-exosome components in wound infection healing: new insights.

Fakouri A, Razavi Z, Mohammed A, Abdul Hussein A, Afkhami H, Hosseini Hooshiar M Burns Trauma. 2024; 12:tkae021.

PMID: 39139205 PMC: 11319788. DOI: 10.1093/burnst/tkae021.

Exosomes, MDSCs and Tregs: A new frontier for GVHD prevention and treatment.

Hess N, Kink J, Hematti P Front Immunol. 2023; 14:1143381.

PMID: 37063900 PMC: 10090348. DOI: 10.3389/fimmu.2023.1143381.

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

Forsberg M, Kink J, Thickens A, Lewis B, Childs C, Hematti P Stem Cell Res Ther. 2021; 12(1):459.

PMID: 34407878 PMC: 8371870. DOI: 10.1186/s13287-021-02491-7.

Dichotomic Potency of IFNγ Licensed Allogeneic Mesenchymal Stromal Cells in Animal Models of Acute Radiation Syndrome and Graft Host Disease.

Chinnadurai R, Bates P, Kunugi K, Nickel K, DeWerd L, Capitini C Front Immunol. 2021; 12:708950.

PMID: 34386012 PMC: 8352793. DOI: 10.3389/fimmu.2021.708950.

References

Mendicino M, Bailey A, Wonnacott K, Puri R, Bauer S . MSC-based product characterization for clinical trials: an FDA perspective. Cell Stem Cell. 2014; 14(2):141-5. DOI: 10.1016/j.stem.2014.01.013. View

Chinnadurai R, Copland I, Garcia M, Petersen C, Lewis C, Waller E . Cryopreserved Mesenchymal Stromal Cells Are Susceptible to T-Cell Mediated Apoptosis Which Is Partly Rescued by IFNγ Licensing. Stem Cells. 2016; 34(9):2429-42. PMC: 5016228. DOI: 10.1002/stem.2415. View

Cuende N, Rasko J, Koh M, Dominici M, Ikonomou L . Cell, tissue and gene products with marketing authorization in 2018 worldwide. Cytotherapy. 2018; 20(11):1401-1413. DOI: 10.1016/j.jcyt.2018.09.010. View

Shao L, Sun Y, Zhang Z, Feng W, Gao Y, Cai Z . Deletion of proapoptotic Puma selectively protects hematopoietic stem and progenitor cells against high-dose radiation. Blood. 2010; 115(23):4707-14. PMC: 2890171. DOI: 10.1182/blood-2009-10-248872. View

Lange C, Brunswig-Spickenheier B, Cappallo-Obermann H, Eggert K, Gehling U, Rudolph C . Radiation rescue: mesenchymal stromal cells protect from lethal irradiation. PLoS One. 2011; 6(1):e14486. PMC: 3016319. DOI: 10.1371/journal.pone.0014486. View

Maria O, Shalaby M, Syme A, Eliopoulos N, Muanza T . Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis. Cytotherapy. 2016; 18(9):1129-45. DOI: 10.1016/j.jcyt.2016.06.008. View

Rybkina V, Bannikova M, Adamova G, Dorr H, Scherthan H, Azizova T . Immunological Markers of Chronic Occupational Radiation Exposure. Health Phys. 2018; 115(1):108-113. DOI: 10.1097/HP.0000000000000855. View

Chinnadurai R, Sands J, Rajan D, Liu X, Arafat D, Das R . Molecular Genetic and Immune Functional Responses Distinguish Bone Marrow Mesenchymal Stromal Cells from Hepatic Stellate Cells. Stem Cells. 2019; 37(8):1075-1082. PMC: 7102402. DOI: 10.1002/stem.3028. View

Tamarat R, Benderitter M, Jourdain J, Maidment B, Macchiarini F, Rios C . Response to the 'Comments on "Cellular Therapies for Treatment of Radiation Injury after a Mass Casualty Incident" (Radiat Res 2017; 188:242-45)' by Drouet et al. (Letters to the Editor, Radiat Res 2017; 188:463). Radiat Res. 2018; 189(4):446. PMC: 8386944. DOI: 10.1667/RR5LTE.1. View

10.

Simmons P, Przepiorka D, Thomas E, Torok-Storb B . Host origin of marrow stromal cells following allogeneic bone marrow transplantation. Nature. 1987; 328(6129):429-32. DOI: 10.1038/328429a0. View

11.

Reeves G, AINSWORTH E . Description of the chronic radiation syndrome in humans irradiated in the former Soviet Union. Radiat Res. 1995; 142(2):242-3. View

12.

Drouet M, Riccobono D, Francois S . Comments on "Cellular Therapies for Treatment of Radiation Injury after a Mass Casualty Incident" (Radiat Res 2017; 188:242-45). Radiat Res. 2017; 188(4):463. DOI: 10.1667/0033-7587-188.4.463a. View

13.

Su J, Chen X, Huang Y, Li W, Li J, Cao K . Phylogenetic distinction of iNOS and IDO function in mesenchymal stem cell-mediated immunosuppression in mammalian species. Cell Death Differ. 2013; 21(3):388-96. PMC: 3921585. DOI: 10.1038/cdd.2013.149. View

14.

Bartsch K, Al-Ali H, Reinhardt A, Franke C, Hudecek M, Kamprad M . Mesenchymal stem cells remain host-derived independent of the source of the stem-cell graft and conditioning regimen used. Transplantation. 2009; 87(2):217-21. DOI: 10.1097/TP.0b013e3181938998. View

15.

Rieger K, Marinets O, Fietz T, Korper S, Sommer D, Mucke C . Mesenchymal stem cells remain of host origin even a long time after allogeneic peripheral blood stem cell or bone marrow transplantation. Exp Hematol. 2005; 33(5):605-11. DOI: 10.1016/j.exphem.2005.02.004. View

16.

Villaron E, Almeida J, Lopez-Holgado N, Alcoceba M, Sanchez-Abarca L, Sanchez-Guijo F . Mesenchymal stem cells are present in peripheral blood and can engraft after allogeneic hematopoietic stem cell transplantation. Haematologica. 2004; 89(12):1421-7. View

17.

Davies L, Boberg E, Le Blanc K . Commentary: Role of Mesenchymal Stromal Cell-Mediated Crosstalk with Macrophages in Graft-versus-Host Disease and Tissue Repair. Biol Blood Marrow Transplant. 2017; 23(6):861-862. DOI: 10.1016/j.bbmt.2017.04.006. View

18.

Le Blanc K, Davies L . MSCs-cells with many sides. Cytotherapy. 2018; 20(3):273-278. DOI: 10.1016/j.jcyt.2018.01.009. View

19.

Horwitz E, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini F . Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy. 2005; 7(5):393-5. DOI: 10.1080/14653240500319234. View

20.

Wang J, Sun Q, Morita Y, Jiang H, Gross A, Lechel A . A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage. Cell. 2012; 148(5):1001-14. DOI: 10.1016/j.cell.2012.01.040. View