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Author Notes:

Corresponding author: Elizabeth O. Stenger, 1760 Haygood Drive NE, Atlanta, GA 30322; 404-785-1272 (P); 404-785-1421 (F); estenge@emory.edu

Elizabeth O. Stenger and Raghavan Chinnadurai contributed equally to this work.

Authorship Contributions: EOS and RC carried out the majority of the experiments with the assistance of SY and under the guidance of JG; MG provided technical assistance; Fluidigm array experiments and analysis performed by RC with the assistance of DA and under the guidance of GG; EOS and RC wrote the manuscript; JG assisted in writing the manuscript and generation of the figures; LK and GG assisted in editing the manuscript

The content is solely the responsibility of the authors and does not necessarily present the official views of the National Institutes of Health.

Disclosure of Conflicts of Interest: The authors have no conflicts to disclose.

Subjects:

Research Funding:

This work was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award numbers UL1TR000454 and KL2TR000455 (EOS).

This work was also supported by the CHOA Center for Transplantation and Immune-mediated Disorders Pilot Grant (EOS) and an ACTSI ImmunoEngineering Pilot Grant (JG and GG).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Hematology
  • Immunology
  • Transplantation
  • Mesenchymal stromal cells
  • Sickle cell disease
  • Hematopoietic stem cell
  • transplantation
  • Hematopoiesis
  • HEMATOPOIETIC STEM-CELLS
  • GENE-EXPRESSION PROFILE
  • INTERNATIONAL-SOCIETY
  • CONDITIONING REGIMEN
  • APLASTIC-ANEMIA
  • CLINICAL-TRIALS
  • HOST ORIGIN
  • IN-VIVO
  • TRANSPLANTATION
  • BLOOD

Bone Marrow-Derived Mesenchymal Stromal Cells from Patients with Sickle Cell Disease Display Intact Functionality

Tools:

Journal Title:

Biology of Blood and Marrow Transplantation

Volume:

Volume 23, Number 5

Publisher:

, Pages 736-745

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Hematopoietic cell transplantation (HCT) is the only cure for sickle cell disease (SCD), but engraftment remains challenging in patients lacking matched donors. Infusion of mesenchymal stromal cells (MSCs) at the time of HCT may promote hematopoiesis and ameliorate graft-versus-host disease. Experimental murine models suggest MSC major histocompatibility complex compatibility with recipient impacts their in vivo function, suggesting autologous MSCs could be superior to third-party MSCs for promoting HCT engraftment. Here we tested whether bone marrow (BM)-derived MSCs from SCD subjects have comparable functionality compared with MSCs from healthy volunteers. SCD MSC doubling time and surface marker phenotype did not differ significantly from non-SCD. Third-party and autologous (SCD) T cell proliferation was suppressed in a dose-dependent manner by all MSCs. SCD MSCs comparably expressed indoleamine-2,3-dioxygenase, which based on transwell and blocking experiments appeared to be the dominant immunomodulatory pathway. The expression of key genes involved in hematopoietic stem cell (HSC)–MSC interactions was minimally altered between SCD and non-SCD MSCs. Expression was, however, altered by IFN-γ stimulation, particularly CXCL14, CXCL26, CX3CL1, CKITL, and JAG1, indicating the potential to augment MSC expression by cytokine stimulation. These data demonstrate the feasibility of expanding BM-derived MSCs from SCD patients that phenotypically and functionally do not differ per International Society of Cell Therapy essential criteria from non-SCD MSCs, supporting initial evaluation (primarily for safety) of autologous MSCs to enhance haploidentical HSC engraftment in SCD.

Copyright information:

© 2017 The American Society for Blood and Marrow Transplantation

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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