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Mesenchymal Stem Cells Modulate Immune System in GvHD Patients

Carlson, Robert H.

doi: 10.1097/01.COT.0000316085.03570.ce

Abstract 143

ATLANTA—Some predict that all of medicine will be transformed over the next several years by the use of stem cells to repair tissue, reverse the effects of aging, and treat diseases such as cancer, autoimmune diseases, and Alzheimer's.

Today's medical researchers have numerous stem cell populations that might be developed for therapeutic purposes. One of the rarer stem cells, mesenchymal stem cells, were shown in a study presented here at the ASH Annual Meeting to have the ability to dampen the immune system of patients with leukemia who develop graft-versus-host disease (GvHD).

This unusual aspect of cutting-edge stem cell biology used mesenchymal stem cells to treat Grade 3/4 acute and extensive chronic GvHD in leukemia patients following high-dose chemotherapy, radiation, and allogeneic stem-cell transplantation.

Reporting the results, Katarina LeBlanc, MD, PhD, Associate Professor of Hematology in the Center for Allogeneic Stem Cell Transplantation at the Karolinska Institutet in Stockholm, said that nonhematopoietic mesenchymal cells in bone marrow are capable of both self renewal and differentiation into bone, cartilage, muscle, and fat cells.

In a press briefing at the meeting highlighting noteworthy papers, Dr. LeBlanc explained that a key characteristic of mesenchymal stem cells is their ability to inhibit donor T-cells from reacting against the recipient's tissue, and to therefore stave off inflammation.

“In vitro, we have the capacity to differentiate mesenchymal stem cells to other tissues such as adipose, bone, and cartilage,” she said. “But they also appear to have an ability to inhibit T-cell alloreactivity.”

The mesenchymal stem cells used in the study were isolated from marrow aspirate taken from HLA identical siblings, haploidentical donors, and HLA-mismatched third parties. Although mesenchymal cells are rare in the human body, Dr. LeBlanc said younger individuals have more of them than older individuals.

The cells were purified, cultured, and then infused into 16 patients, 14 with severe acute GvHD and two with extensive chronic GvHD. They were treated with one infusion (nine patients), two infusions (six patients), or three infusions (one patient) of the prepared mesenchymal stem cells.

The median dose was 1.0 ×106 cells/kg of body weight of the recipient. In six of the severe acute cases, the GvHD completely resolved; four had partial resolution; two did not respond; and two died very quickly and could not be evaluated.

The two patients with extensive chronic GvHD had transient responses. No side effects were seen after the mesenchymal stem cell infusions.

“This is a study of a very small number of patients, but it is a good start for us to initiate a larger clinical trial,” Dr. LeBlanc said.

The moderator of the session at which the study was presented, Stephen G. Emerson, MD, PhD, Chief of the Hematology-Oncology Division and Associate Director for Clinical Research at the University of Pennsylvania Cancer Center, noted that GvHD is very difficult to treat in allogeneic bone marrow transplant patients.

“But this therapy shuts [the GvHD] down,” he said. “Mesenchymal stem cells are very potent suppressor cells that can dampen all sorts of responses. It sounds magical but it actually has worked.”

Dr. Emerson said that in situations where the immune system is overactive—GvHD, rheumatoid arthritis, chronic active hepatitis, Crohn's disease, and lupus erythematosus, to name a few—it is possible to grow mesenchymal cells from patients' marrow, purify them, and simply give them back intravenously.

“They home to where they are needed and dampen the overactive immune responses.”

© 2006 Lippincott Williams & Wilkins, Inc.
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