Intravenous grafts recapitulate the neurorestoration afforded by intracerebrally delivered multipotent adult progenitor cells in neonatal hypoxic-ischemic rats.
Once hypoxic-ischemic (HI) injury ensues in the human neonate at birth, the resulting brain damage lasts throughout the individual's lifetime, as no ameliorative treatments are currently available. We have recently shown that intracerebral transplantation of multipotent adult progenitor cells (MAPCs) results in behavioral improvement and reduction in ischemic cell loss in neonatal rat HI-injury model. In an attempt to advance this cellular therapy to the clinic, we explored the more practical and less invasive intravenous administration of MAPCs. Seven-day-old Sprague-Dawley rats were initially subjected to unilateral HI injury, then 7 days later received intracerebral or intravenous injections of allogeneic rat MAPCs. On post-transplantation days 7 and 14, the animals that received MAPCs via the intracerebral or intravenous route exhibited improved motor and neurologic scores compared with those that received vehicle infusion alone. Immunohistochemical evaluations at day 14 after transplantation revealed that both intracerebrally and intravenously transplanted MAPCs were detected in the ischemic hippocampal area. The degree of hippocampal cell preservation was almost the same in the two treatment groups and greater than that in the vehicle group. These results show that intravenous delivery of MAPCs is a feasible and efficacious cell therapy with potential for clinical use.
Yasuhara
Takao
T
Department of Neurology, Medical College of Georgia, Augusta, Georgia 30912-3200, USA.
Hara
Koichi
K
Maki
Mina
M
Mays
Robert W
RW
Deans
Robert J
RJ
Hess
David C
DC
Carroll
James E
JE
Borlongan
Cesar V
CV
D000818:Animals; D000831:Animals, Newborn; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D015925:Cryopreservation; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology*; D020925:Hypoxia-Ischemia, Brain / Q000601:surgery*; D007150:Immunohistochemistry; D009043:Motor Activity; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012677:Sensation / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods