Human Peripheral Blood Mononucleocyte Derived Myeloid Committed Progenitor Cells Mitigate H-ARS by Exosomal Paracrine Signal.

Creator(s)

Rishi Man Chugh
Payel Bhanja
Ximena Diaz Olea
Fang Tao, Children's Mercy HospitalFollow
Kealan Schroeder, Children's Mercy Kansas CityFollow
Ryan Zitter
Tanu Arora
Harsh Pathak
Bruce F. Kimler
Andrew K. Godwin
John M. Perry, Children's Mercy HospitalFollow
Subhrajit Saha

Document Type

Article

Publication Date

5-14-2022

Identifier

DOI: 10.3390/ijms23105498; PMCID: PMC9142131

Abstract

Radiation-induced loss of the hematopoietic stem cell progenitor population compromises bone marrow regeneration and development of mature blood cells. Failure to rescue bone marrow functions results in fatal consequences from hematopoietic injury, systemic infections, and sepsis. So far, bone marrow transplant is the only effective option, which partially minimizes radiation-induced hematopoietic toxicities. However, a bone marrow transplant will require HLA matching, which will not be feasible in large casualty settings such as a nuclear accident or an act of terrorism. In this study we demonstrated that human peripheral blood mononuclear cell-derived myeloid committed progenitor cells can mitigate radiation-induced bone marrow toxicity and improve survival in mice. These cells can rescue the recipient's hematopoietic stem cells from radiation toxicity even when administered up to 24 h after radiation exposure and can be subjected to allogenic transplant without GVHD development. Transplanted cells deliver sEVs enriched with regenerative and immune-modulatory paracrine signals to mitigate radiation-induced hematopoietic toxicity. This provides a natural polypharmacy solution against a complex injury process. In summary, myeloid committed progenitor cells can be prepared from blood cells as an off-the-shelf alternative to invasive bone marrow harvesting and can be administered in an allogenic setting to mitigate hematopoietic acute radiation syndrome.

Journal Title

Int J Mol Sci

Volume

23

Issue

10

MeSH Keywords

Acute Radiation Syndrome; Animals; Bone Marrow; Hematopoietic Stem Cells; Humans; Leukocytes, Mononuclear; Mice; Peripheral Blood Stem Cells

Keywords

PBMC; bone marrow; irradiation; mouse models; myeloid; stem/progenitor cells

Comments

Grant support

• U01AI138323/NH/NIH HHS/United States
• P20GM130423/GM/NIGMS NIH HHS/United States
• P30 CA168524/CA/NCI NIH HHS/United States

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Publisher's Link: https://www.mdpi.com/1422-0067/23/10/5498

Recommended Citation

Chugh RM, Bhanja P, Olea XD, et al. Human Peripheral Blood Mononucleocyte Derived Myeloid Committed Progenitor Cells Mitigate H-ARS by Exosomal Paracrine Signal. Int J Mol Sci. 2022;23(10):5498. Published 2022 May 14. doi:10.3390/ijms23105498