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Front. Med. | doi: 10.3389/fmed.2018.00037

Post-Transplant Intramuscular Injection of PLX-R18 Mesenchymal-like Adherent Stromal Cells Improves Human Hematopoietic Engraftment In A Murine Transplant Model

 Leland Metheny1*, Saada Eid2, Karen Lingas2,  Racheli Ofir3, Lena Pinzur3, Howard Meyerson4,  Hillard M. Lazarus1 and  Alex Y. Huang5
  • 1Stem Cell Transplant Program, University Hospitals of Cleveland, United States
  • 2Case Western Reserve University, United States
  • 3Pluristem Therapeutics (Israel), Israel
  • 4Pathology, Case Western Reserve University, United States
  • 5Division of Pediatric Hematology/Oncology, Dept. of Pediatrics, Rainbow Babies & Children's Hospital, United States

Late term complications of hematopoietic cell transplantation (HCT) are numerous and include incomplete engraftment. One possible mechanism of incomplete engraftment after HCT is cytokine-mediated suppression or dysfunction of the bone marrow microenvironment. Mesenchymal stromal cells (MSC) elaborate cytokines that nurture or stimulate the marrow microenvironment by several mechanisms. We hypothesize that the administration of exogenous MSCs may modulate the bone marrow milieu and improve peripheral blood count recovery in the setting of incomplete engraftment. In the current study, we demonstrated that post-transplant intramuscular administration of human placental derived mesenchymal-like adherent stromal cells (PLX-R18) harvested from a 3-dimensional in vitro culture system improved post-transplant engraftment of human immune compartment in an immune-deficient murine transplantation model. As measured by the percentage of CD45+ cell recovery, we observed improvement in the peripheral blood counts at weeks 6 (8.4% vs. 24.1%, p <0.001) and 8 (7.3% vs. 13.1%, p<0.05) and in the bone marrow at week 8 (28% vs. 40.0%, p <0.01) in the PLX-R18 cohort. As measured by percentage of CD19+ cell recovery, there was improvement at weeks 6 (12.6% vs. 3.8%) and 8 (10.1% vs. 4.1%). These results suggest that PLX-R18 may have a therapeutic role in improving incomplete engraftment after HCT.

Keywords: Cord Blood Stem Cell Transplantation, Mesenchymal Stromal Cells, Hematopoietic Stem Cell Transplantation, Engraftment, Post-transplant complications

Received: 11 Oct 2017; Accepted: 31 Jan 2018.

Edited by:

Meral Beksac, Ankara University, Turkey

Reviewed by:

Pinar Yurdakul, TOBB University of Economics and Technology, Turkey
Kamil C. Akcali, Ankara University Medical School, Turkey  

Copyright: © 2018 Metheny, Eid, Lingas, Ofir, Pinzur, Meyerson, Lazarus and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Leland Metheny, University Hospitals of Cleveland, Stem Cell Transplant Program, Cleveland, 44106, Ohio, United States, leland.metheny@uhhospitals.org