Autologous Mesenchymal Stem Cells Transplantation for Spinal Cord Injury- A Phase I Clinical Study

The role of regenerative therapies has gained more importance due to increased number of SCI in the wake of recent anti-terrorism operations by the armed forces and non-availability of any curative treatment for this category of patients. The promising results of preliminary clinical trials have proved that adult stem cells especially multipotent mesenchymal stromal cells can be safely injected and well tolerated and have shown functional improvement in SCI patients. The successful treatment in these patients will not only improve functional status of these otherwise debilitating patients, but can also reduce the burden on health care facilities. Mesenchymal stem cells have been shown to promote anatomical and functional recovery in animal models of SCI by promoting tissue sparing, axonal regeneration, and remyelination. Therapeutic effects of MSCs are primarily due to the secretion of soluble factors and the provision of extracellular matrix that provide protection and support repair. MSC are attractive candidates for transplantation into human patients because they can be easily harvested, expanded and banked, or derived directly from the patient allowing for autologous transplantation, obviating the need for immune suppression. In this study patients suffering from sub-acute and chronic phase of spinal cord injury shall be included. Patients will undergo detailed screening through MRI and motor and sensory assessment by ASIA score. Further evaluation will include electromyography (EMG) and tests for electroneurophysiological assessment like nerve conduction velocity (NCV) will also be done. Bone marrow aspiration will be done from iliac crest of the patients, followed by mononuclear cells (MNCs) separation by density gradient centrifugation. MNCs will be washed and cultured in tissue culture flasks. After 48 hours non-adherent cells will be removed from culture. Medium will be changed twice weekly till MSCs reach 70-80 % confluence. At that point MSCs will be harvested and after microbiological and other quality control testing the cellular preparation will be diluted to final concentration and infused by intrathecal injection.

Primary outcome measure is safety which will be determined by clinical evaluation by two independent neurologists during one month of hospital stay after receiving treatment course.

Secondary outcome measures will include American Spinal Injury Association (ASIA) impairment scale and NCV/EMG.

Inclusion criteria

• Patients suffering from sub-acute and chronic phase of spinal cord injury
• Traumatic spinal cord injury at the thoracic level
• American Spinal Injury Association (ASIA) impairment scale "A"
• Confirmation by MRI of injury level
• Time between injury and enrollment greater than 2 weeks
• Ability to provide informed consent

Exclusion criteria

• Axonic brain injury
• Inability to provide consent
• Open injuries
• Active infectious diseases
• Terminal patients
• Neurodegenerative diseases
• Evidence of meningitis
• Cerebral palsy
• Primary haematologic diseases
• Coagulopathies
• Pregnancy
• Other medical complications that contra-indicate surgery, including major respiratory complications
• Use of metal implants close to vascular structures (such as cardiac pacemaker or prosthesis) that contraindicate MRI.