Stem Cell Transplantation for Stroke: Future Vision or Today’s Reality?
abstracts & commentary
Sources: Kondziolka D, et al. Transplantation of cultured human neuronal cells for patients with stroke. Neurology 2000;55:565-569; Zivin JA. Cell transplant therapy for stroke: Hope or hype. Neurology 2000;55:467.
Current treatment strategies for acute ischemic stroke are limited to revascularization with thrombolytic therapy and neuroprotective agents. The former is restricted to a narrow time window and the latter has failed to show promise in numerous agents with multiple trials.
The potential for late improvement following stroke created much fanfare this past year when Liepert and associates published data using limb restriction to improve function of paralytic limbs (Stroke 2000;31:1210-1216; Plum F. Neurology Alert 2000;18:83-84). In the current report, Kondziolka and colleagues enter into the novel world of tissue transplantation, using cultured human neurons injected into the basal ganglia of stroke victims to restore neurologic function.
In a limited, phase I study, Kondziolka et al treated 12 patients with chronic effects of stroke (infarcts 6 months-6 years in age). Subjects received either "single pass" injection, with 2 million cells inserted into the area of infarct or "three pass" injection, with 6 million cells implanted. The neuronal cells (LBS-Layton Bioscience), were produced from the NT2/D1 human embryonic carcinoma derived cell line. These cells differentiate into neurons by the addition of 10 uM of retinoic acid.
Kondziolka et al found that six of the 12 patients showed improvement on the European Stroke Scale (ESS). The mean improvement was 2.9 points (P = 0.046). There was a suggestion of a positive dose effect that was not statistically signficant. As many patients had no change or worsened (6/12) as showed improvement. No improvement was demonstrated on other outcome measures such as the NIH-SS and Barthel Index. Survival of implanted cells was suggested by PET scanning which showed increased metabolic activity in 50% of patients.
Overall, the procedure was demonstrated to be safe. Reversible renal failure related to cyclosporine occurred in one patient. A single seizure and one recurrent stroke occurred, but these were not thought to be procedure related.
Commentary
As Zivin notes in the accompanying editorial, these data are extremely preliminary, and Kondziolka et al are careful not to make any extravagant claims. The LBS-neurons, derived from a cancer cell line, have shown no evidence of malignant transformation in multiple animal models. Nevertheless, such safety concerns will persist.
The study was not designed to demonstrate efficacy, and it is reassuring that the procedure did not produce adverse effects on quality of life. —Alan Z. Segal
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