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Updated: Mar 29, 2026
Assessment of the Immunomodulatory Properties of Human Mesenchymal Stem Cells MSCs
Published on: December 24, 2015
Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia
S Geyh1,2, M Rodríguez-Paredes2,3, P Jäger1
1Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.
Abstract:
Hematopoietic insufficiency is the hallmark of acute myeloid leukemia (AML) and predisposes patients to life-threatening complications such as bleeding and infections. Addressing the contribution of mesenchymal stromal cells (MSC) to AML-induced hematopoietic failure we show that MSC from AML patients (n=64) exhibit significant growth deficiency and impaired osteogenic differentiation capacity. This was molecularly reflected by a specific methylation signature affecting pathways involved in cell differentiation, proliferation and skeletal development. In addition, we found distinct alterations of hematopoiesis-regulating factors such as Kit-ligand and Jagged1 accompanied by a significantly diminished ability to support CD34+ hematopoietic stem and progenitor cells in long-term culture-initiating cells (LTC-ICs) assays. This deficient osteogenic differentiation and insufficient stromal support was reversible and correlated with disease status as indicated by Osteocalcin serum levels and LTC-IC frequencies returning to normal values at remission. In line with this, cultivation of healthy MSC in conditioned medium from four AML cell lines resulted in decreased proliferation and osteogenic differentiation. Taken together, AML-derived MSC are molecularly and functionally altered and contribute to hematopoietic insufficiency. Inverse correlation with disease status and adoption of an AML-like phenotype after exposure to leukemic conditions suggests an instructive role of leukemic cells on bone marrow microenvironment.
Insights
Mesenchymal stromal cells (MSCs) from acute myeloid leukemia (AML) patients show impaired growth and differentiation, contributing to hematopoietic failure. These defects are reversible and linked to disease status, suggesting leukemia cells instruct MSC dysfunction.
Area of Science:
- Hematology
- Cancer Biology
- Stem Cell Biology
Background:
- Hematopoietic insufficiency is a critical feature of acute myeloid leukemia (AML), increasing risks of bleeding and infection.
- Mesenchymal stromal cells (MSCs) play a crucial role in regulating hematopoiesis within the bone marrow microenvironment.
Purpose of the Study:
- To investigate the functional and molecular alterations of MSCs in AML patients.
- To determine the contribution of these altered MSCs to AML-induced hematopoietic failure.
- To explore the reversibility of MSC defects and the influence of leukemic cells on MSCs.
Main Methods:
- Analysis of MSC growth, osteogenic differentiation, and methylation signatures in 64 AML patients.
- Assessment of hematopoiesis-regulating factors (Kit-ligand, Jagged1) and support for CD34+ hematopoietic stem and progenitor cells (HSPCs) using long-term culture-initiating cell (LTC-IC) assays.
- In vitro experiments culturing healthy MSCs in conditioned medium from AML cell lines.
Main Results:
- AML-derived MSCs exhibited significant growth deficiency and impaired osteogenic differentiation, linked to specific methylation changes.
- Reduced support for HSPCs in LTC-IC assays and altered levels of key hematopoiesis regulators were observed.
- MSC dysfunction was reversible, correlating with disease status, and healthy MSCs adopted an AML-like phenotype when exposed to leukemic cell conditioned medium.
Conclusions:
- MSCs from AML patients are molecularly and functionally impaired, contributing to the disease's hematopoietic insufficiency.
- The reversibility of MSC defects and their response to leukemic cell conditioned medium suggest an instructive role for leukemia cells in altering the bone marrow microenvironment.
Related Concept Videos
01:19Mesenchymal Stem Cells
01:01Regulation of Hematopoietic Stem Cells