Therapeutic Effects of Intra-Arterial Delivery of Bone Marrow Stromal Cells in Traumatic Brain Injury of Rats—In Vivo Cell Tracking Study by Near-Infrared Fluorescence Imaging

Neurosurgery:
February 2012 - Volume 70 - Issue 2 - p 435–444
doi: 10.1227/NEU.0b013e318230a795
Research-Animal

Osanai, Toshiya MD, PhD*; Kuroda, Satoshi MD, PhD*; Sugiyama, Taku MD, PhD*; Kawabori, Masahito MD*; Ito, Masaki MD*; Shichinohe, Hideo MD, PhD*; Kuge, Yuji PhD‡; Houkin, Kiyohiro MD, PhD*; Tamaki, Nagara MD, PhD‡; Iwasaki, Yoshinobu MD, PhD*

Abstract

BACKGROUND: A noninvasive and effective route of cell delivery should be established to yield maximal therapeutic effects for central nervous system (CNS) disorders.

OBJECTIVE: To elucidate whether intra-arterial delivery of bone marrow stromal cells (BMSCs) significantly promotes functional recovery in traumatic brain injury (TBI) in rats.

METHODS: Rat BMSCs were transplanted through the ipsilateral internal carotid artery 7 days after the onset of cortical freezing injury. The BMSCs were labeled with fluorescent dye, and in vivo optical imaging was employed to monitor the behaviors of cells for 4 weeks after transplantation. Motor function was assessed for 4 weeks, and the transplanted BMSCs were examined using immunohistochemistry.

RESULTS: In vivo optical imaging and histologic analysis clearly demonstrated that the intra-arterially injected BMSCs were engrafted during the first pass without systemic circulation, and the transplanted BMSCs started to migrate from the cerebral capillary bed to the injured CNS tissue within 3 hours. Intra-arterial BMSC transplantation significantly promoted functional recovery after cortical freezing injury. A subgroup of BMSCs expressed the phenotypes of neurons, astrocytes, and endothelial cells around the injured neocortex 4 weeks after transplantation.

CONCLUSION: Intra-arterial transplantation may be a valuable option for prompt, noninvasive delivery of BMSCs to the injured CNS tissue, enhancing functional recovery after TBI. In vivo optical imaging may provide important information on the intracerebral behaviors of donor cells by noninvasive, serial visualization.