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

Evgenia Volinsky, Astar Lazmi-Hailu, Nerel Cohen, Boaz Adani, Mohammad Faroja, Myriam Grunewald*, Raphael Gorodetsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Purpose: Selected 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 materials: f-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 conclusions: The 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.

Original languageAmerican English
Article number337
JournalStem Cell Research and Therapy
Volume11
Issue number1
DOIs
StatePublished - 3 Aug 2020

Bibliographical note

Publisher Copyright:
© 2020 The Author(s).

Keywords

  • Acute radiation syndrome (ARS)
  • Bone marrow
  • C3H mice
  • Extra-medullary hematopoiesis (EMH)
  • Fetal human placental stromal cells (f-hPSCs)
  • Hematopoiesis
  • Hematopoietic stem cells (HSC)
  • Spleen

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