Chronergy of umbilical cord blood-mesenchymal stem cell transplantation for treatment of hypoxic-ischemic brain damage

Xiaohua YAN; Ruibin HUANG

ABSTRACT

BACKGROUND:

Mesenchymal stem cell transplantation for treatment of hypoxic-ischemic brain damage (HIBD) has obtained some outcomes in adult animals, but studies are few in neonatal animal models. Mesenchymal stem cells are commonly harvested from bone marrow. A few studies are on umbilical cord blood-mesenchymal stem cells (UCB-MSCs).

OBJECTIVE:

To investigate the feasibility and timeliness of UCB-MSC transplantation after injecting UCB-MSCs into neonatal rat models of HIBD. DESIGN, TIME AND

SETTING:

The complete randomized controlled animal experiment was performed at the Laboratory of Department of Neurology of First Hospital Affiliated to Nanchang University from October 2004 to July 2005. MATERIALS A total of 38 healthy neonatal SD rats aged 7 days old were used to create rat models of HIBD. Three rats died.

METHODS:

Cord blood samples were collected after normal full-term delivery of 23-35 healthy pregnant women for culturing UCB-MSCs. MSCs were labeled with 4',6-diamidino-2-phenylindole 2hci (DAPI) in vitro before transplantation. Thirty-five rat models were divided into three groups. UCB-MSCs were injected into tail vein of twelve rat models in the early transplantation group two days after modeling. UCB-MSCs were injected into tail vein of twelve rat models in the late transplantation group one week after modeling. Same volume of saline was injected into eleven rats of the control group. Six rats from early transplantation and late transplantation groups each were respectively obtained at day 2 after transplantation and at week 2 after modeling. Three, four and four rats from control group were obtained respectively 2 days, 1 and 2 weeks after modeling, and sacrificed after anaesthesia. Ischemic brain tissues from the brain and hippocampal gyrum were sliced into frozen sections. MAIN OUTCOME

MEASURES:

Brain tissue pathomorphology was measured by Haematoxylin and Eosin Staining. Brain tissue DAPI-positive cells were detected with a fluorescence microscope.

RESULTS:

Brain edema at ischemic region, neural cell swelling and a decrease in cell number were tested in the control group. DAPI-positive UCB-MSCs were few in focal brain tissues, and swelling degree,extracellular space improvement and increased cell number were insignificant in the early transplantation group. One week after modeling, brain tissue extracellular space became small, cell number increased, and brain swelling reduced; A mass of DAPI-positive cells in rat focal brain migrated and diffused, without significant boundary in the late transplantation group.

CONCLUSION:

UCB-MSCs effectively traverse blood-brain barrier, and migrate, disperse and conform around focal brain tissues. A good outcome of transplantation is obtained at week 1 after HIBD.