Intravenous autologous bone marrow mononuclear stem cell therapy for ischemic stroke: a multicentric, randomized trial.
OBJECTIVE
Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke.


METHODS
This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National Institute of Health Stroke Scale (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area of (18)fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days.


RESULTS
Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset. There was no significant difference between BMSCs arm and control arm in the Barthel Index score (63.1 versus 63.6; P=0.92), modified Rankin scale shift analysis (P=0.53) or score >3 (47.5% versus 49.2%; P=0.85), NIHSS score (6.3 versus 7.0; P=0.53), change in infarct volume (-11.1 versus -7.36; P=0.63) at day 180. Adverse events were also similar in the 2 arms, and no patient showed any new area of (18)fluorodeoxyglucose uptake.


CONCLUSIONS
With the methods used, results of this hitherto first randomized controlled trial indicate that intravenous infusion of BMSCs is safe, but there is no beneficial effect of treatment on stroke outcome.


BACKGROUND
URLs: http://ctri.nic.in/Clinicaltrials and http://www.clinicaltrials.gov. Unique identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177.
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.). drkameshwarprasad@gmail.com.
Kameshwar
K
Prasad
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Alka
A
Sharma
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Ajay
A
Garg
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Sujata
S
Mohanty
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Shinjini
S
Bhatnagar
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Sharat
S
Johri
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Kunwar Karni
KK
Singh
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Velu
V
Nair
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Ravi Shankar
RS
Sarkar
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Sankar Prasad
SP
Gorthi
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Kaukab Maqbool
KM
Hassan
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Sudesh
S
Prabhakar
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Neelam
N
Marwaha
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Niranjan
N
Khandelwal
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Usha Kant
UK
Misra
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Jayantee
J
Kalita
From the All India Institute of Medical Sciences, New Delhi, India (K.P., A.G., S.M., S.B.); Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (A.S.); Army Hospital Research & Referral, New Delhi, India (S.J., K.K.S., V.N.); Armed Forces Medical College, Pune, India (R.S.S., S.P.G., K.M.H.); Postgraduate Institute of Medical Education & Research, Chandigarh, India (S.P., N.M., N.K.); and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (U.K.M., J.K., S.N.).
Soniya
S
Nityanand
D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function; D020521:Stroke / Q000473:pathology / Q000601:surgery*
adult stem cells; bone marrow cells; cell- and tissue-based therapy; cerebral infarction; randomized controlled trial; stem cell transplantation; stroke