Stem cell delivery by lumbar puncture as a therapeutic alternative to direct injection into injured spinal cord.

OBJECT: Using cellular transplants to treat spinal cord injury is a promising therapeutic strategy, but transplants grafted directly into the injury site can further damage the already compromised cord. To avoid additional trauma and to simplify translation to the clinic, it is advantageous to use less invasive delivery methods. METHODS: The authors compared the efficacy of intrathecal cell delivery at the lumbar region (lumbar puncture [LP]) to direct injection into a thoracic contusion injury using a mixed population of lineage-restricted neural precursor cells. RESULTS: Direct injection resulted in a higher volume of neural precursor cells located throughout the injury site, whereas fewer LP-delivered cells accumulated at the dorsal aspect of the injured cord. Both grafting methods were neuroprotective, resulting in reduction of injury size and greater tissue sparing compared with controls. Functional recovery was evaluated by assessing motor and bladder function. Animals that received cells via direct injection performed significantly better in the open-field locomotor test than did operated controls, while LP-treated animals showed intermediate recovery of function that did not differ statistically from that of either operated controls or directly injected animals. Bladder function, however, was significantly improved in both directly injected and LP-treated animals. CONCLUSION: Grafting of stem cells via LP resulted in localized accumulation of cells at the injury site, neuroprotection, and modest recovery of function. Further optimization of the LP procedure by increasing the number of cells that are delivered and determining the optimal delivery schedule may further improve recovery to levels comparable to direct injection.

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.