Autologous Bone Marrow Mononuclear Cells for Spinal Cord Injury- A Case Report.
Background: Patients with Spinal cord compression following traumatic vertebrae fractures lead a life with paraplegia in most instances. They are usually treated to stabilize the vertebrae fractures by surgical means and mobilized in a wheelchair. We are reporting a case of a 23 year old male, who became paraplegic following a compression fracture of D12 vertebrae (that was surgically corrected), and improved significantly after treatment with autologous bone marrow mononuclear cells (ABMMC) injection.
Materials & Method: Immediately after the injury sustained by a fall from a height of 12 Mts, the patient developed total paraplegia (complete loss of sensation and motor functions of his lower half and bladder/ bowel control). He was completely wheel-chair bound. 60 days post-injury, he had made no significant neurological recovery. Bladder drainage was by indwelling catheter and bowel evacuation was accomplished by digital method. 72 days post-injury he received an injection of 190 million ABMMCs into D12 sub-arachnoid space. 100 ml of bone marrow was tapped and the mononuclear cells were isolated. CD34+ and CD45+ cell count and endotoxin assay was done before injection. Clinical assessment of motor, sensory functions and urodynamic study were periodically done.
Results: Two months after therapy, patient has shown significant neurological recovery. Motor power has improved from 0/5 to 4/5 and able to walk independently. Pain and temperature sensations have returned in both lower limbs except over the posterior side of both thighs. He appreciates bladder fullness and can hold urine for up to 2 Hrs.
Conclusion: Intrathecal injection of ABMMCs at the site of spinal cord injury is non-toxic and may have possibly helped to hasten neurological recovery which otherwise may not have been expected in this short span.
Autologous stem cells for spinal cord injury.
We studied 100 patients with spinal cord injury after autologous stem cell injection in the spinal fluid with a follow up of 6months post-stem cell injection.
There were 69 males and 31 females, age ranging from 8 to 55 years. Time after spinal injury ranged from 11 years to 3 months (average: 4.5 years). The level of injury ranging upper thoracic (T1-T7): 34 patients; lower thoracic: 45 patients; lumbar: 12 patients; cervical: 9 patients. All patients had an MRI scan, urodynamic study and somatosensory evoked potential tests before and 3 months after stem cell injection.
A total of 80% of patients had grade zero power in the lower limbs and the rest had grade 1-2 power before stem cell injections.
We extracted CD34 and CD 133 marked stem cells from 100 ml of bone marrow aspirate using Ficoll gradient method with cell counting done using flow cytometry. In aseptic conditions, 15 ml of stem cell concentrate was injected into the lumbar spinal fluid. The CD34/CD45 counts ranged from 120 to 500 million cells in the total volume.
After 6 months, post-injection, eight patients had two grades of motor power improvement, 12 had sensory tactile and pain perception improvement in bladder control and bladder muscle contractility. A total of 12 patients had reported or observed improvement in neurological status. Of patients, 85% who had motor improvement had lesions below T8. MRI, somatosensory- evoked potential and urodynamic study data will be presented.
Conclusion: This study shows that quantitative and qualitative improvement in the neurological status of paralyzed patients after spinal cord injury is possible after autologous hematological stem cell injections in select patients. Further studies to identify mechanism of action of stem cells on nerve tissue both in vivo and in vitro will be necessary to confirm the above results.
Autologous Stem Cell Injection for Spinal Cord Injury- A Clinical Study from India.
Abstract: We studied 100 patients with Spinal Cord injury (SCI) after Autologous Stem cell Injection in the Spinal fluid with a Follow up of 6 months post Stem cell injection. There were 69 males and 31 females; age ranging from 8 years to 55 years. Time after Spinal Injury ranged from 11 years - 3 months (Average: 4.5 years). The Level of Injury ranged from Upper Thoracic (T1-T7) - 34 pts, Lower thoracic (T7-T12) -45 pts, Lumbar -12, Cervical-9 pts. All patients had an MRI Scan, urodynamic study and SSEP (somatosensory Evoked Potential) tests before and 3 months after Stem cell Injection.
80% of patients had Grade 0 power in the Lower limbs and rest had grade 1-2 power before stem cell injections. 70% of cases had complete lack of Bladder control and 95% had reduced detrusor function.
We Extracted CD34 and CD 133 marked Stem cells from 100 ml of Bone marrow Aspirate using Ficoll Gradient method with Cell counting done using flowcytometry.15 ml of the Stem cell concentrate was injected into the Lumbar spinal fluid in aseptic conditions. The CD 34/CD45 counts ranged from 120-400 million cells in the total volume.
6 months after Injection, 8 patients had more than 2 grades of Motor power improvement, 3 are able to walk with support. 1 patient with T12/L1 injury was able to walk without support. 12 had sensory tactile and Pain perception improvement and 8 had objective improvement in bladder control and Bladder Muscle contractility. A total of 18 patients had reported or observed improvement in Neurological status. 85% of patients who had motor Improvement had Lesions below T8. MRI, SSEP and Urodynamic Study data are gathered at regular intervals.
Conclusion: This study shows that Quantitative and qualitative Improvement in the Neurological status of paralyzed patients after Spinal cord injury is possible after autologous bone marrow Stem cell Injections in select patients. There was no report of Allodynia indicating the safety of the procedure. Further studies to (i) quantify the neurological and vascular damage and to standardize the dosage, (ii) Identify Mechanism of action of each group of Stem cells (HSCs, MSCs, Naive cells, Purified subsets etc) on Nerve Tissue both In-vivo and In-vitro will be necessary to Confirm Above results.
Autologous Stem Cell Injections for Spinal cord Injury-A multicentric Study with 6 month follow up of 108 patients
Background: Most patients who sustain Traumatic vertebral injuries and resultant spinal cord compression are doomed to a life either a quadriplegia or paraplegia. Current treatment option is stabilization of the vertebral fracture by surgical means to prevent further deterioration and wishful waiting for recovery. In most instances recovery is insignificant. We had earlier reported an index case of a 23 year old male who sustained a compression fracture of D 12 vertebrae (that was surgically corrected) and improved significantly after treatment with Autologous Bone Marrow Mononuclear Cells (ABMMC). He had improved to achieve significant neurological recovery (became independently mobile, sensations had largely returned and had developed reasonable bladder control). We have subsequently used ABMMC treatment in 108 patients at different centers whose data is presented below.
Materials and Methods: Patients were drawn from 5 centers across Chennai, Tamil Nadu. 100 to 120 ml of Bone marrow was tapped from the right posterior iliac crest under local anesthesia in an operating theater room. The bone marrow was preserved in Anticoagulant citrate dextrose bag and transported in cold chain storage to NCRM lab where it was processed under cGMP Sop’s Class 10000 clean room and class 100 biosafety hood. The stem cells were counted under Neubaur’s hemocytometer; double-checked with phase contrast inverted microscope and CD34+ cells estimated by flow cytometry. The stem cells were injected intrathecally into the subaracnoid space of the patients below L2 level.
Result: No. of patients: 108 (76 males, 32 females)
Age group range: 8 yrs to 55 yrs.
Folllow up attrition rate: 14.02%
Level of injury- Cervical (13 no.) Upper Thorax-T1-T7 (35 no.) Lower thorax T8-T12 (46no.) Lumbar (2 no.)
Motor power improvement by (atleast 2 grade of power post injection) – 12 patients (14.11% of the followed up patients).
Motor power improvement resulting in functional recovery- 4 (3 walk with support, 1 walking without support, 4.70% of the followed up patients).
Subjective sensory improvement – 14 (16.97% of the followed up patients).
Abnormal sensation- 0%
Autonomic improvement by urodynamic studies- 8 patients (9.41% of the followed up patients).
Limitations: 1. Follow up data on 14% of patients could not be obtained, as they were lost to follow up.
2. Sensory improvement was obtained only by subjective testing. Objective measures such as SSEP could not be used.
3. It is an observational study and not a case-control study.
Conclusions: Out of the 108 patients in whom the ABMMC was used, none of the patients had any adverse reaction to the cells, atleast 14.11% of patients reported atleast 2 grades of improvement in motor power and 4.7% of patient were able to walk independently. 16.47% of patients reported subjective sensory improvement, none of the patients had abnormal sensations such as allodynia. 9.41% of patients had improvement as documented by urodynamic studies. The factors determining outcome which could be the age of patients, level of injury, tine interval between injury and ABMMC injection, dosage of stem cells injected etc., need to be evaluated in future studies.
Intralesional Application of Autologous Bone Marrow Stem Cells with Scaffold in Canine for Spinal Cord Injury
A three year old male non-descriptive companion dog was presented to the Small Animal Orthopedic Unit of Madras Veterinary College Teaching Hospital (MVC) with paraplegia of fourth degree neurological deficit of hind limbs due to automobile trauma.
Radiographic views were suggestive of dislocation at T8-T9 vertebral segment with fracture of L2 vertebra. Myelography confirmed the signs of abrupt stoppage of the contrast column cranial to dislocated area and was interpretive of transected spinal cord at L2 level. Construct was prepared with bone marrow mononuclear cells (BMMNC) isolated from bone marrow aspirate of femur and the cells were seeded in Thermoreversible Gelatin Polymer (TGP) at the cell processing facility of Nichi-In Centre for Regenerative Medicine (NCRM) as per GMP protocols and was engrafted after hemilaminectomy and durotomy procedures in the MVC. Postoperatively the animal was clinically stable; however the animal died on the 7th day. Autopsy revealed co-morbid conditions like cystitis, nephritis and transmissible venereal tumor. Histopathology of the engrafted area revealed sustainability of aggregated stem cells that were transplanted revealing an ideal biocompatibility of the construct prepared with bone marrow mononuclear cells and polymer hydrogel for spinal cord regeneration in dogs. Further studies in similar cases will have to be undertaken to prove the long term efficacy.