Functional recovery after transplantation of bone marrow-derived human mesenchymal stromal cells in a rat model of spinal cord injury.
OBJECTIVE
Spinal cord injury (SCI) is a medically untreatable condition for which stem cells have created hope. Pre-clinical and clinical studies have established that these cells are safe for transplantation. The dose dependency, survivability, route of administration, cell migration to injury site and effect on sensory and motor behavior in an SCI-induced paraplegic model were studied.


METHODS
A spinal cord contusion injury model was established in rats. Bone marrow (BM) mesenchymal stromal cells (MSC) were tagged to facilitate tracing in vivo. Two different doses (2 and 5 million cells/kg body weight) and two different routes of infusion (site of injury and lumbar puncture) were tested during and after the spinal shock period. The animals were tested post-transplantation for locomotor capacity, motor control, sensory reflex, posture and body position. Stem cell migration was observed 1 month post-transplantation in spinal cord sections.


RESULTS
The overall results demonstrated that transplantation of BM MSC significantly improved the locomotor and sensory behavior score in the experimental group compared with the sham control group, and these results were dose dependent. All the infused stem cells could be visualized at the site of injury and none was visualized at the injected site. This indicated that the cells had survived in vivo, were probably chemoattracted and had migrated to the lesion site.


CONCLUSIONS
MSC transplanted with a lumbar puncture method migrate to the site of injury and are the most suitable for SCI healing. These cells demonstrate a dose-dependent effect and promote functional recovery when injected during or after the spinal shock period.
Pal
Rakhi
R
Stempeutics Research Pvt Ltd, Manipal Hospital, Bangalore, India.
Gopinath
Chaitanya
C
Rao
Nagesh M
NM
Banerjee
Poulomi
P
Krishnamoorthy
Venkatesh
V
Venkataramana
Neelam K
NK
Totey
Satish
S
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002465:Cell Movement; D002478:Cells, Cultured; D002985:Clinical Protocols; D004195:Disease Models, Animal; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009043:Motor Activity; D051381:Rats; D020127:Recovery of Function; D012018:Reflex; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation