Background:
Recent breakthrough in cell therapy is expected to reverse the neurological sequelae of stroke. We investigated the safety and feasibility of intracerebral transplantation of autologous BMSC in the subacute phase of stroke (RAINBOW trial). Several new aspects including cell labeling and tracking, socioecomonic analysis using QALY, and the use of human platelet lysate instead of fetal bovine serum were adopted. (UNIN ID: UMIN000026130)
Methods/Design:
This is a phase 1, open-label, uncontrolled, dose-response study enrolling adults with severe motor deficits (mRS>3) 14 days after stroke. Approximately 50 mL of the bone marrow is extracted from the iliac bone of each patient 15 days or later from the onset, and BMSCs are cultured with allogeneic human platelet lysate (PL) and are labeled with superparamagnetic iron oxide for cell tracking using MRI. BMSCs are stereotactically administered around the area of infarction approximately 2 months from the ischemic stroke. Each patient will be administered a dose of 20 or 50 million cells. Neurological scoring, MRI for cell tracking,
18
F-fuorodeoxyglucose positron emission tomography, and
123
I-Iomazenil single photon emission computed tomography will be performed throughout 1 year after the administration.
Results:
All 7 patients have been successfully finished transplantation, and there was no severe adverse event in any of the patient regarding the surgical procedure nor cell quality. Favorable motor recoveries (change in mRS
>
1) are seen in 5 of 7 patients, and cell engraftment and migration to ischemic site was also observed.
Discussion:
This is a first-in-human trial to use labelled BMSC to the patients with subacute ischemic stroke. Intracerebral transplantation of autologous BMSC is safe and well tolerated. Cell migration to the ischemic boundary can clarify the therapeutic mechanisms.
Whole and fractionated human platelet lysate biomaterials-based biotherapy induces strong neuroprotection in experimental models of amyotrophic lateral sclerosis
