Paper # (a-korea Research Foundation)

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1 Paper # Is There Any Improvement After Receiving Autologous Bone Marrow Cell Transplantation and Bone Marrow Stimulation with Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) in Complete Spinal Cord Injury Patients? Report of Three Cases Yoon Ha, MD, PhD, Seung Hwan Yoon, MD, PhD, So Ra Park, MD, PhD, Do Heum Yoon, MD, PhD, Hyun Sun Park, MD, PhD, Hyung Chun Park, MD, PhD (Seoul, Korea) (a-korea Research Foundation) INTRODUCTION: The transplantation of bone marrow cells into the injured spinal cord has been found to improve neurologic functions in experimental animals. However, it is unclear whether bone marrow cells can similarly improve the neurologic functions of complete spinal cord injury patients. To study their therapeutic effects in human spinal cord injury (SCI), we transplanted autologous bone marrow cells into the SCI sites and administered granulocyte macrophage-colony stimulating factor (GM-CSF) in three complete SCI patients. METHODS: Bone marrow cell transplantation with GM-CSF administration was performed on two patients (patients1 and 2), wherein concentrated bone marrow cell pastes were injected into the injury area using a sterile 21 gauge fine needle. The total volume of bone marrow cells injected was 1.8 ml (cell concentration 1.1X10 6 /ul). Patient 3 was administered GM-CSF only. The follow up periods were 5 months (patient 1), 4 months (patient 2) and 6 months (patient 3). All cases are summarized in Table 1 and Figure 1. RESULTS: Sensory improvements were followed immediately after the operations. Sensory recovery in the sacral segment was noticed at 3 weeks (patient 1), 13 days (patient 2) and at 2 months (patient 3) postoperatively. Significant motor improvements were noticed at 3 months in patients 1 and 2, and at 4 months in patient 3. All three patients showed neurologic improvements at the last follow up 5,4 and 6months respectively (Frankel grade C, AIS grade C). Electromyography shows voluntary low extremity muscle contractions in all three patients. Follow up magnetic resonance imaging showed slight enhancement within the zone of the bone marrow cell transplantation (Figure 2). Functional MRI reveals activation of sensory cortex after somatosensory stimulation of low extremity (Figure 3). CONCLUSION: All three cases in our study showed a neurologic improvement to Frankel C, though our results are still less significant to determine therapeutic 55

2 efficacy. Long-term and more comprehensive clinical studies are required to determine the therapeutic effects of bone marrow cells in SCI patients. Table 1. Summary of cases (* AIS: American spinal injury association impairment scale) Case 1 Case2 Case3 Sex male male male Age(year) Level of injury C6/7 C6/7 C6/7 Bone marrow cell 7 7 none transplantation date(days after trauma) Number of GM-CSF administration cycle(times) Associated Injury None Aortic dissection Maleolar fracture Lt Frankel grade A B A (72hr after admission) AIS * grade A A A (72hr after admission) Time to AIS grade B 3 2(13days) 8 (weeks after trauma) Time to AIS grade C (months after trauma) Follow up duration(months) Last F/U AIS grade C C C MRI enhancement enhancement Increase T2 signal Complication 56

3 Figure Legends Figure 1 Preoperative radiologic findings. (a-1) Axial computed tomography scan through the C6 region and (a-2) sagittal T2W magnetic resonance(mr) image in case 1, who suffered cervical cord injury at C6/7 level - showing spinal canal narrowing and diffuse edema in the spinal cord. (b-1) Sagittal T1W and (b-2) T2W MR image in case 2, who suffered a traumatic ruptured disc at C6/7. The ruptured disc C6/7 is shown and is associated with slight cord expansion and a diffuse spinal cord edema. (c-1) Sagittal postcontrast T1W and (c-2) T2W MR image in a patient who suffered a fracture dislocation of C6/7. The spinal cord is expanded and enhanced at the injured level. 57

4 Figure 2. Follow-up MRI findings. (a-1) Sagittal T1W magnetic resonance(mr) image, (a-2) corresponding postcontrast image and (a-3)sagittal T2W MR image at 5 months postoperatively in case1, showing a small patch enhancement in the bone marrow cell transplantation area. (b-1) Sagittal T1W MR image,(b-2) corresponding postcontrast image and (b- 3)sagittal T2W MR image at 4 months postoperatively in case2, showing a small linear enhancement in the bone marrow cell transplantation area. (c-1) Sagittal T1W MR image,(c-2) corresponding postcontrast image and (c- 3)sagittal T2W MR image in case3, showing a small non-enhanced well defined cyst in the cord, which is associated with a slight cord expansion and adjacent myelomalacia. 58

5 Figure 3. Functional MRI Functional MRI findings (case 1) after transplantation with autologous bone marrow cells and GM-CSF treatment. The imagines are obtained after stimulation of right foot tactile stimulation. a-1 and a-2 are preoperative functional MRI findings. There is no evidence of somatosensory cortex activation by stimulation of right foot. b-1 and b-2 are postoperative 3months functional MRI findings. Increased blood flow in left somatosensory cortex is observed. If noted, the author indicates something of value received. The codes are identified as: a- research or institutional support; b- miscellaneous funding; c- royalties; d- stock options; e- consultant or employee; n- no conflicts disclosed, and * disclosure not available at the time of printing. For full information, refer to inside of back cover. 59