Autologous Mesenchymal Stem Cells Transplantation for Spinal Cord Injury- A Phase I Clinical Study
Condition: Spinal Cord Injury
MeSH terms: Spinal Cord Injuries; Wounds and Injuries
Study type: Interventional
Phase: Phase 1

Summary: 
      The conventional treatment of spinal cord injury (SCI) includes physical therapy and
      rehabilitation and in some cases may require surgical intervention. Although improved
      emergency care and aggressive treatment can help in preventing further damage and even
      restore minimal sensory functions, still a large proportion of patients suffer with prolonged
      disabilities. It led neurologists to search out for new treatment options for this otherwise
      debilitating disorder. Recent advances in research have developed a better understanding of
      stem cell biology especially their role in tissue repair and regeneration. Encouraging
      results in pre-clinical phase and limited human trials have proved that stem cells can be
      safely and effectively delivered to the injured site for regeneration of damaged tissue.
      Although a variety of cell types have been tried for their role in repair of spinal cord
      injury, majority of clinical trials employed stem cells taken from bone marrow especially
      mesenchymal stromal cells (MSC). Bone marrow MSCs are a good choice for regenerative
      therapies owing to advantages like ease of collection and ex-vivo culturing, immune tolerance
      and their ability to differentiate into a variety of cell types including neuronal lineage
      cells. Intravenous application or direct injection of MSCs into cerebrospinal fluid (CSF) via
      lumber puncture in animal models of SCI and brain trauma had shown that MSCs can migrate
      towards and integrate into injured spinal tissue and reduce cyst size and increase functional
      recovery. The literature indicates that acute, sub-acute and chronic injury can be a
      therapeutic target for MSC grafting. The mechanism of action may however vary among these
      conditions. In acute phase, MSC administration play anti-inflammatory role, while in
      sub-acute/chronic setting it may be used as neurostimulator and for cell bridging effect and
      possibly glial or neuronal cell replacement. The investigators propose a non-randomized,
      single group, open label, phase-I, interventional study to evaluate the safety and efficacy
      of intrathecal delivery of patient's own (autologous) bone marrow mesenchymal stem cells for
      treatment of spinal cord injury. This will include determination of functional recovery
      (neuro-muscular control and sensation) in the affected area and overall improvement in
      quality of life of the patients and also take into account any side effects, if observed.
    

Detailed description: 
      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.
    

Intervention name(s): mesenchymal stem cells
Intervention type(s): Biological
Intervention description(s): autologous transplantation of mesenchymal stem cells in spinal cord injury patients
Other intervention name(s): MSC
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Spinal cord injury; mesenchymal stem cells; transplantation