Umbilical cord-derived mesenchymal stem cells with forced expression of hepatocyte growth factor enhance remyelination and functional recovery in a rat intracerebral hemorrhage model.
BACKGROUND
Spontaneous intracerebral hemorrhage (ICH) carries a high mortality rate, with survivors commonly left with permanent neurological deficits. Mesenchymal stem cell (MSC) transplantation promotes functional recovery in experimental ICH, and treatment with hepatocyte growth factor (HGF) is beneficial in ischemic stroke.


OBJECTIVE
We hypothesize that transplantation of MSCs with previous transduction of HGF has an additive effect in promoting neurological recovery through myelin and axonal regeneration.


METHODS
HGF transduction to human umbilical cord-derived MSCs using lentiviral plasmid pWPI-HGF-GFP was prepared. One week after a collagenase-induced ICH, 80 male Sprague-Dawley rats were divided into 3 groups for stereotactic injection of phosphate-buffered saline (group I), MSC transplant (group II), and HGF-transduced MSC transplant (group III), respectively, into the left ventricle. The animals were assessed weekly for 5 weeks using the Rotarod motor function test, at which time they were killed for Luxol fast blue myelin staining and appropriate immunohistochemistry and Western blotting.


RESULTS
Animals receiving transplanted HGF-transduced MSCs (group III) exhibited significantly better motor function recovery than animals treated with MSCs alone (group II), which in turn performed better than the phosphate-buffered saline controls at 2 weeks after transplantation. Luxol fast blue staining of myelin displayed significantly less demyelination and significantly higher reactivity in myelin basic protein and growth-associated protein-43 in immunohistochemistry and Western blotting and significantly reduced myelin-associated glycoprotein activity in group III animals.


CONCLUSIONS
Animals transplanted with HGF-transduced MSCs 1 week after experimental ICH were shown to achieve a better neurological recovery. This improved neurological recovery from ICH is attributed to nerve fiber remyelination and axonal regeneration.
Liu
An Min
AM
Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong.
Lu
Gang
G
Tsang
Kam Sze
KS
Li
Guo
G
Wu
Yan
Y
Huang
Zheng Song
ZS
Ng
Ho Keung
HK
Kung
Hsiang Fu
HF
Poon
Wai Sang
WS
D000818:Animals; D015153:Blotting, Western; D036101:Cord Blood Stem Cell Transplantation; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D020300:Intracranial Hemorrhages / Q000601:surgery*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009186:Myelin Sheath / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology; D004856:Postural Balance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D014161:Transduction, Genetic
D017228:Hepatocyte Growth Factor