Umbilical cord-derived mesenchymal stem cells with forced expression of hepatocyte growth factor enhance remyelination and functional recovery in a rat intracerebral hemorrhage model
Authors: Wai Sang Poon
Hsiang Fu Kung
Gang Lu
Ho Keung Ng
Yan Wu
Guo Li
An Min Liu
Kam Sze Tsang
Zheng Song Huang
Journal: Neurosurgery (2010)
Discipline: CLINICAL MEDICINE
Keywords: Intracerebral hemorrhage; Mesenchymal stem cells; Hepatocyte growth factor; Transplantation; Neurological recovery
Affiliations: Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong., Division of Neurosurgery, Department of Surgery, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong, Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong, Department of Anatomy, Capital Medical University, Beijing, China, Department of Neurosurgery, First Affiliated Hospital, Sun Yat Sen University, Guangzhou, China, Li Ka Shing Institute of Health Sciences, Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong

Abstract:  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. Conclusion: 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. 

Retracted: No

PubPeer comments:
 Beta-actin in Figure 7E and 8 look identical, just the intensity was changed: ![file] ,