Lumbar puncture delivery of bone marrow stromal cells in spinal cord contusion: a novel method for minimally invasive cell transplantation.
Cell transplantation as a treatment for spinal cord injury is a promising therapeutic strategy whose effective clinical application would be facilitated by non-invasive delivery protocols. Cells derived from the bone marrow are particularly attractive because they can be obtained easily, expanded to large numbers and potentially used for autologous as well as allogeneic transplantation. In this study we tested the feasibility of a novel minimally invasive method--lumbar puncture (LP)--for transplanting bone marrow stromal stem cells (MSC) into a clinically relevant spinal cord contusion model. We further sought to determine optimal protocols for performing such minimally invasive cell transplantation. Sprague-Dawley rats received a moderate contusion injury at the midthoracic level followed by LP transplantation of MSC derived from transgenic rats that express the human placental alkaline phosphatase (AP) reporter gene. The recipients were analyzed histologically to evaluate the extent of cell delivery and survival at the injury site. We found that MSC delivered by LP reached the contused spinal cord tissues and exerted a significant beneficial effect by reducing cyst and injury size. Transplantation within 14 days of injury provided significantly greater grafting efficiency than more delayed delivery, and increasing MSC dosage improved cell engraftment. The techniques described here can easily be translated to patients, thus accelerating clinical application of stem cell therapies.
Bakshi
Ajay
A
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
Barshinger
Alissa L
AL
Swanger
Sharon A
SA
Madhavani
Vinit
V
Shumsky
Jed S
JS
Neuhuber
Birgit
B
Fischer
Itzhak
I
D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology; D013119:Spinal Cord Injuries / Q000628:therapy*; D013129:Spinal Puncture / Q000379:methods*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology; D017154:Stromal Cells / Q000637:transplantation*; D013997:Time Factors; D016896:Treatment Outcome
D000469:Alkaline Phosphatase