Cord Blood-Derived Endothelial Progenitor Cells Promote In Vivo Regeneration of Human Hematopoietic Bone Marrow.

Abstract

PURPOSE:

Victims of acute radiation exposure are susceptible to hematopoietic toxicity due to bone marrow damage and loss of mature blood elements. Here, we evaluated cord blood-derived endothelial progenitor cells (CB-EPCs) as a potential cellular therapy for mitigation of hematologic acute radiation syndrome. CB-EPCs express endothelial cell markers and maintain their growth characteristics beyond 10+ passages without diminishing their doubling capacity. Further, CB-EPCs can be cryopreserved in vapor-phase liquid nitrogen and easily recovered for propagation, making them an attractive nonimmunogenic cellular therapy for off-the-shelf use. Importantly, we show CB-EPCs have the capacity to potently expand adult human bone marrow hematopoietic progenitor cells both in vitro and in vivo.

METHODS AND MATERIALS:

To demonstrate the role of CB-EPCs in promoting in vivo human immune reconstitution after irradiation, we employed a novel humanized mouse model established by transplant of CD34+ bone marrow cells from 9 unique adult organ donors into immunocompromised NSG-SGM3 mice. The response of the humanized immune system to ionizing irradiation was then tested by exposure to 1 Gy followed by subcutaneous treatment of CB-EPCs, Food and Drug Administration-approved growth factor pegfilgrastim (0.3 mg/kg), or saline.

RESULTS:

At day 7, total human bone marrow was decreased by 80% in irradiated controls. However, treatment with either growth factor pegfilgrastim or CB-EPCs increased recovery of total human bone marrow by 2.5-fold compared with saline. Notably, CB-EPCs also increased recovery of both human CD34+ progenitors by 5-fold and colony-forming capacity by 3-fold versus saline. Additionally, CB-EPCs promoted recovery of endogenous bone marrow endothelial cells as observed by both increased vessel area and length compared with saline.

CONCLUSIONS:

These findings indicate the feasibility of using humanized mice engrafted with adult bone marrow for radiation research and the development of CB-EPCs as an off-the-shelf cellular therapy for mitigation of hematologic acute radiation syndrome.

• Authors: Phuong L Doan, Anne C Frei, Sadhna O Piryani, Nathan Szalewski, Elizabeth Fan, Heather A Himburg
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 116 Issue 5 Pg. 1163-1174 (Aug 01 2023) ISSN: 1879-355X [Electronic] United States
• PMID: 36792018 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Intercellular Signaling Peptides and Proteins

Topics

• Adult
• Humans
• Mice
• Animals
• Bone Marrow
• Hematopoietic Stem Cells (physiology)
• Endothelial Progenitor Cells
• Fetal Blood (metabolism)
• Acute Radiation Syndrome (metabolism)
• Bone Marrow Cells
• Intercellular Signaling Peptides and Proteins (metabolism)
• Hematopoietic Stem Cell Transplantation (methods)