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

Area of Science:

• Hematology
• Immunology
• Cell Therapy

Background:

• Hematopoietic cell transplantation (HCT) is the only cure for sickle cell disease (SCD).
• Engraftment challenges persist in HCT for SCD patients without matched donors.
• Mesenchymal stromal cells (MSCs) may improve HCT outcomes by promoting hematopoiesis and reducing graft-versus-host disease.

Purpose of the Study:

• To compare the functionality of bone marrow (BM)-derived MSCs from SCD subjects with those from healthy volunteers.
• To assess the feasibility of using autologous MSCs to enhance HCT engraftment in SCD.

Main Methods:

• Compared doubling time and surface marker phenotype of SCD and non-SCD MSCs.
• Assessed T cell proliferation suppression by autologous (SCD) and third-party MSCs.
• Measured indoleamine-2,3-dioxygenase (IDO) expression and its role in immunomodulation.
• Analyzed gene expression related to hematopoietic stem cell (HSC)-MSC interactions, with and without IFN-γ stimulation.

Main Results:

• SCD MSCs exhibited comparable doubling times and phenotypes to non-SCD MSCs.
• All tested MSCs dose-dependently suppressed T cell proliferation, with IDO identified as a key mechanism.
• Gene expression related to HSC-MSC interactions showed minimal differences between SCD and non-SCD MSCs.
• IFN-γ stimulation significantly altered the expression of specific genes (e.g., CXCL14, JAG1) in MSCs.

Conclusions:

• BM-derived MSCs from SCD patients are phenotypically and functionally comparable to those from healthy donors.
• Autologous MSCs meet essential criteria and support their evaluation for enhancing haploidentical HSC engraftment in SCD.
• Further research, focusing on safety, is warranted for autologous MSCs in SCD HCT.