Aug 26, 2002
By Karla Gale
A simple intravenous infusion of human bone marrow stromal cells reduces brain cell loss and improves functional recovery in a rat model of ischemic stroke, Michigan investigators report in the August 27 issue of Neurology.
Dr. Michael Chopp, of Henry Ford Hospital in Detroit, and colleagues note that marrow stromal cells are multipotent progenitor cells that can cross the blood-brain barrier. They investigated the effect of human marrow stromal cells (hMSC) in male rats after 2-hour occlusion of the middle cerebral artery to induce stroke. One day later, nine animals were injected i.v. with 3 million human bone marrow stromal cells, while nine were injected i.v. with 3 million rat liver fibroblasts. Ten rats received no treatment.
On day 14 after occlusion, the researchers assessed the animals using a modified neurologic severity score (mNSS) incorporating tests of motor, sensory and reflex function, as well as an "adhesive-removal dot test." Scores on both tests were significantly improved among rats injected with hMSC compared with the two groups of control rats (p < 0.05).
At 7 days post-stroke, hMSC-treated animals secreted nearly double the levels of brain-derived neurotrophic factor, 969 pg/mL, compared with that from the other two groups of animals, 434 and 498 pg/mL. Nerve growth factor was also increased in the stromal cell-treated rats, 1227 versus 834 and 980 pg/mL (p < 0.05 for both trophic factors).
Within a reference coronal 6- m-thick section, the number of apoptotic cells was reduced by almost half by the stromal cell infusion, 38.5 versus 82.6 and 76.4. Immunohistochemical analysis of brain sections revealed that stromal cells were distributed throughout the ischemic damaged brain of recipient rats, especially in the ischemic boundary zone.
"Human stromal cells are at least as good if not better than those of other animals, giving a more robust response," Dr. Chopp told Reuters Health. He also called "provocative" the lack of rejection of the stromal cell infusion by the recipient rats, "suggesting we may be able to explore allogeneic cell transfer in human patients."
Dr. Chopp noted that it would require about 2 weeks to sufficiently amplify autologous bone marrow stromal cells from patients. "Ideally, it would be great to have cells 'on the shelf,' ready to treat patients when they come in," he noted.
He pointed out that previously published data from his group suggests that treatment at 1 week post-stroke provides an even better response than that achieved by treatment at 1 day. "This suggests the therapeutic time window for this type of treatment is much greater than for other agents [such as tissue plasminogen activator]."
The Michigan group has received funding for a large preclinical study using this technique, and it is submitting applications for a phase I trial.
Dr. Chopp maintains that this therapeutic approach has shown similar efficacy in animal models of traumatic brain and spinal cord injury and Parkinson's disease, and that their next step is to try it for multiple sclerosis. He stressed that "this type therapy has to be attempted in all neurological disorders."
In an accompanying editorial, Drs. David A. Rempe, of the University of Rochester in New York, and Thomas A. Kent, of the University of Texas in Galveston, write that the beneficial effect of hMSCs "involves actions other than replacement of lost neurons."
In fact, they add, "Because MSC preferentially home to damaged brain, MSC could serve as vectors to deliver substances that promote recovery."
© 2002 Reuters Ltd