Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 59, Num. 4, 2011, pp. 553-554

Neurology India, Vol. 59, No. 4, July-August, 2011, pp. 553-554

Topic of the issue: Editorial

Stem cell therapy for brain disorders: Why results are discordant?

Kameshwar Prasad

Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
Correspondence Address: Kameshwar Prasad, Prof. Kameshwar Prasad, 704, Department of Neurology, CN Centre, AIIMS, New Delhi, India, kp0704@gmail.com

Date of Submission: 11-May-2011
Date of Decision: 15-May-2011
Date of Acceptance: 16-May-2011

Code Number: ni11169

PMID: 21891932

DOI: 10.4103/0028-3886.84336

Discovery of stem cells has generated unparallel hope and expectation for patients suffering from disabling brain diseases, including trauma, stroke, Alzheimer's disease, multiple sclerosis, Parkinson's disease, and others. Preclinical studies in rodent models of these diseases have shown mixed results-some favorable while some unfavorable. In this month's issue of Neurology India, Moorthy et al. ^[1] report a study in a cryoinjury rodent model of head trauma and report no statistically significant benefit with the use of mesenchymal stem cells. This is discordant with many other published preclinical studies which show benefit. They discus many reasons for the discordant results, including timing of infusion of stem cells, nature of the model, sample size, and blinding of measurements. An interesting finding is that results from blinded measurements show lower trend of benefit than unblinded measurements of outcome.

As the field of stem cells grows, increase in the number of reported preclinical and clinical studies is certain. There is also bound to be inconsistency among the various reports. The plausible reasons for such inconsistency besides chance, are type of patients or models, timing and nature of stem cell transplantation, dose of stem cells, whether the studies are randomized or nonrandomized, whether measurements are blinded or unblinded, types and timing of outcome measures, and whether the follow-up is complete or incomplete. Most of these issues are still unresolved in the field of brain disorders. Moreover, human studies often turn out to yield different results from preclinical studies. The classical example has been the lessons learnt from neuroprotection trials in stroke. While several animal studies usually showed encouraging results, none passed the test of clinical trials.

The question of timing of stem cell transplantation has been repeatedly debated. In this issue also Moorthy et al. ^[1] talk of hostile environment in the early stages of trauma that is potentially injurious for stem cells. They argue that infusion at later stages may promote survival of stem cells and hence more benefit. These are theoretical arguments that need to be put to test and resulting data should guide our action, not the theoretical arguments. The stem cells need to be tested in various stages of the disease and the final outcome should guide us regarding the timing for stem cell transplantation. It turns out that most of the studies infusing stem cells in acute stages have yielded positive results suggesting that hostile environment theory is of limited validity. The preclinical data at current stage shows that stem cell transplantation in acute stage of stroke and traumatic brain injury ^[2] is beneficial. It is quite possible that Moorthy et al. ^[1] might have missed the benefit because of delay in the timing of stem cell transplantation.

A number of future studies will be required before the various issues mentioned above are sorted out for stem cell therapy for brain disorders. Even though expectations of patients calls for rapid delineation of relevant factors and clear roadmap for harvesting the benefit of stem cell therapy in brain disorders, it seems likely that several years of hard work will be necessary before therapy becomes practical for patients suffering from brain disorders. In this context, we have recently completed a controlled study with 120 patients with stroke funded by Department of Biotechnology, Government of India. Its results are being analyzed. ^[3]

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