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Alleviation of acute radiation-induced bone marrow failure in mice with human fetal placental stromal cell therapy

Authors
  • Volinsky, Evgenia1, 2
  • Lazmi-Hailu, Astar1
  • Cohen, Nerel1
  • Adani, Boaz1
  • Faroja, Mohammad3
  • Grunewald, Myriam2
  • Gorodetsky, Raphael1
  • 1 Hadassah - Hebrew University Medical Center, Jerusalem, 91120, Israel , Jerusalem (Israel)
  • 2 Hebrew University School of Medicine, Jerusalem, 91121, Israel , Jerusalem (Israel)
  • 3 Hadassah – Hebrew University Medical Center, Jerusalem, Israel , Jerusalem (Israel)
Type
Published Article
Journal
Stem Cell Research & Therapy
Publisher
Springer Nature America, Inc
Publication Date
Aug 03, 2020
Volume
11
Issue
1
Identifiers
DOI: 10.1186/s13287-020-01850-0
Source
Springer Nature
Keywords
License
Green

Abstract

PurposeSelected placental mesenchymal stromal cells isolated from the fetal mesenchymal placental tissues (f-hPSCs) were tested as cell therapy of lethal acute radiation syndrome (ARS) with bone marrow regeneration and induced extramedullary hematopoiesis.Methods and materialsf-hPSCs were isolated from the chorionic plate of human placentae and further expanded in regular culture conditions. 2 × 106 f-hPSCs were injected on days 1 and 4 to 8-Gy total body irradiated (TBI) C3H mice, both intramuscularly and subcutaneously. Pre-splenectomized TBI mice were used to test the involvement of extramedullary spleen hematopoiesis in the f-hPSC-induced hematopoiesis recovery in the TBI mice. Weight and survival of the mice were followed up within the morbid period of up to 23 days following irradiation. The role of hematopoietic progenitors in the recovery of treated mice was evaluated by flow cytometry, blood cell counts, and assay of possibly relevant growth factors.Results and conclusionsThe survival rate of all groups of TBI f-hPSC-treated mice at the end of the follow-up was dramatically elevated from < 10% in untreated to ~ 80%, with a parallel regain of body weight, bone marrow (BM) recovery, and elevated circulating progenitors of blood cell lineages. Blood erythropoietin levels were elevated in all f-hPSC-treated mice. Extramedullary splenic hematopoiesis was recorded in the f-hPSC-treated mice, though splenectomized mice still had similar survival rate. Our findings suggest that the indirect f-hPSC life-saving therapy of ARS may also be applied for treating other conditions with a failure of the hematopoietic system and severe pancytopenia.

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