Chronic spinal cord injury treated with transplanted autologous bone marrow-derived mesenchymal stem cells tracked by magnetic resonance imaging: a case report

Journal of Medical Case Reports

Kittipong Sujirattanawimol²  Adisak Wongkajornsilp¹  Pipat Chiewvit⁴  Monchai Ruangchainikom³  Areesak Chotivichit³ 

[1] Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Rd, Bangkoknoi 10700, Bangkok, Thailand;Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Rd, Bangkoknoi 10700, Bangkok, Thailand;Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Rd, Bangkoknoi 10700, Bangkok, Thailand;Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Rd, Bangkoknoi 10700, Bangkok, Thailand

关键词: Tracking;    Magnetic resonance imaging;    Superparamagnetic iron oxide;    Mesenchymal stem cells;    Spinal cord injury;   

Others  :  1180760
DOI  :  10.1186/s13256-015-0535-6

 received in 2014-09-18, accepted in 2015-01-28,  发布年份 2015

【 摘 要 】

Introduction

Intrathecal transplantation is a minimally invasive method for the delivery of stem cells, however, whether the cells migrate from the lumbar to the injured cervical spinal cord has not been proved in humans. We describe an attempt to track bone marrow-derived mesenchymal stem cells in a patient with a chronic cervical spinal cord injury.

Case presentation

A 33-year-old Thai man who sustained an incomplete spinal cord injury from the atlanto-axial subluxation was enrolled into a pilot study aiming to track bone marrow-derived mesenchymal stem cells, labeled with superparamagnetic iron oxide nanoparticles, from intrathecal transplantation in chronic cervical spinal cord injury. He had been dependent on respiratory support since 2005. There had been no improvement in his neurological function for the past 54 months. Bone marrow-derived mesenchymal stem cells were retrieved from his iliac crest and repopulated to the target number. One half of the total cells were labeled with superparamagnetic iron oxide nanoparticles before transplantation to the intrathecal space between L4 and L5. Magnetic resonance imaging studies were performed immediately after the transplantation and at 48 hours, two weeks, one month and seven months after the transplantation. His magnetic resonance imaging scan performed immediately after the transplantation showed hyposignal intensity of paramagnetic substance tagged stem cells in the subarachnoid space at the lumbar spine area. This phenomenon was observed at the surface around his cervical spinal cord at 48 hours. A focal hyposignal intensity of tagged bone marrow-derived stem cells was detected at his cervical spinal cord with magnetic resonance imaging at 48 hours, which faded after two weeks, and then disappeared after one month. No clinical improvement of the neurological function had occurred at the end of this study. However, at 48 hours after the transplantation, he presented with a fever, headache, myalgia and worsening of his motor function (by one grade of all key muscles by the American Spinal Injury Association impairment scale), which lasted for 48 hours.

Conclusion

Intrathecal injection of bone marrow-derived stem cells at the lumbar spine level could deliver the cells to the injured cervical spinal cord. Transient complications should be observed closely in the first 48 hours after transplantation. Further study should be carried out to evaluate the result of the treatment.

【 授权许可】

   
2015 Chotivichit et al.; licensee BioMed Central.

【 图 表 】

Figure 7.

Figure 2.

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【 参考文献 】

• [1]McDonald JW, Liu XZ, Qu Y, Liu S, Mickey SK, Turetsky D et al.. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med. 1999; 5:1410-2.
• [2]Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res. 2000; 61:364-70.
• [3]Hofstetter CP, Schwarz EJ, Hess D, Widenfalk J, El Manira A, Prockop DJ et al.. Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci U S A. 2002; 99:2199-204.
• [4]Zurita M, Vaquero J. Bone marrow stromal cells can achieve cure of chronic paraplegic rats: functional and morphological outcome one year after transplantation. Neurosci Lett. 2006; 402:51-6.
• [5]Fan L, Du F, Cheng BC, Peng H, Liu SQ. Migration and distribution of bone marrow stromal cells in injured spinal cord with different transplantation techniques. Chin J Traumatol. 2008; 11:94-7.
• [6]Bakshi A, Hunter C, Swanger S, Lepore A, Fischer I. Minimally invasive delivery of stem cells for spinal cord injury: advantages of the lumbar puncture technique. J Neurosurg. 2004; 1:330-7.
• [7]Satake K, Lou J, Lenke LG. Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue. Spine. 2004; 29:1971-9.
• [8]Bakshi A, Barshinger AL, Swanger SA, Madhavani V, Shumsky JS, Neuhuber B et al.. Lumbar puncture delivery of bone marrow stromal cells in spinal cord contusion: a novel method for minimally invasive cell transplantation. J Neurotrauma. 2006; 23:55-65.
• [9]Shi E, Kazui T, Jiang X, Washiyama N, Yamashita K, Terada H et al.. Intrathecal injection of bone marrow stromal cells attenuates neurologic injury after spinal cord ischemia. Ann Thorac Surg. 2006; 81:2227-33.
• [10]Ohta M, Suzuki Y, Noda T, Ejiri Y, Dezawa M, Kataoka K et al.. Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation. Exp Neurol. 2004; 187:266-78.
• [11]Nakano N, Nakai Y, Seo TB, Homma T, Yamada Y, Ohta M et al.. Effects of bone marrow stromal cell transplantation through CSF on the subacute and chronic spinal cord injury in rats. PLoS One. 2013; 8:e73494.
• [12]Bull E, Madani SY, Sheth R, Seifalian A, Green M, Seifalian AM. Stem cell tracking using iron oxide nanoparticles. Int J Nanomedicine. 2014; 9:1641-53.
• [13]Sykova E, Jendelova P, Herynek V. MR tracking of stem cells in living recipients. Methods Mol Biol. 2009; 549:197-215.
• [14]Jasmin XX, Torres AL, Nunes HM, Passipieri JA, Jelicks LA, Gasparetto EL et al.. Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging. J Nanobiotechnol. 2011; 9:4. BioMed Central Full Text
• [15]Arbab AS, Yocum GT, Rad AM, Khakoo AY, Fellowes V, Read EJ et al.. Labeling of cells with ferumoxides-protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells. NMR Biomed. 2005; 18:553-9.
• [16]Balakumaran A, Pawelczyk E, Ren J, Sworder B, Chaudhry A, Sabatino M et al.. Superparamagnetic iron oxide nanoparticles labeling of bone marrow stromal (mesenchymal) cells does not affect their “stemness”. PLoS One. 2010; 5:e11462.
• [17]Saito F, Nakatani T, Iwase M, Maeda Y, Murao Y, Suzuki Y et al.. Administration of cultured autologous bone marrow stromal cells into cerebrospinal fluid in spinal injury patients: a pilot study. Restor Neurol Neurosci. 2012; 30:127-36.
• [18]Jiang PC, Xiong WP, Wang G, Ma C, Yao WQ, Kendell SF et al.. A clinical trial report of autologous bone marrow-derived mesenchymal stem cell transplantation in patients with spinal cord injury. Exp Ther Med. 2013; 6:140-6.
• [19]Callera F, de Melo CM. Magnetic resonance tracking of magnetically labeled autologous bone marrow CD34+ cells transplanted into the spinal cord via lumbar puncture technique in patients with chronic spinal cord injury: CD34+ cells’ migration into the injured site. Stem Cells Dev. 2007; 16:461-6.
• [20]Li L, Jiang W, Luo K, Song H, Lan F, Wu Y et al.. Superparamagnetic iron oxide nanoparticles as MRI contrast agents for non-invasive stem cell labeling and tracking. Theranostics. 2013; 3:595-615.
• [21]Song F, Tian M, Zhang H. Molecular imaging in stem cell therapy for spinal cord injury. Biomed Res Int. 2014; 2014:759514.
• [22]Sandu N, Spiriev T, Schaller B. Stem cell transplantation in neuroscience: the role of molecular imaging. Stem Cell Rev. 2012; 8:1265-6.
• [23]Li Z, Suzuki Y, Huang M, Cao F, Xie X, Connolly AJ et al.. Comparison of reporter gene and iron particle labeling for tracking fate of human embryonic stem cells and differentiated endothelial cells in living subjects. Stem Cells. 2008; 26:864-73.
• [24]Spiriev T, Sandu N, Schaller B. Molecular imaging and tracking stem cells in neurosciences. Methods Mol Biol. 2013; 1052:195-201.
• [25]Kishk NA, Gabr H, Hamdy S, Afifi L, Abokresha N, Mahmoud H et al.. Case control series of intrathecal autologous bone marrow mesenchymal stem cell therapy for chronic spinal cord injury. Neurorehabil Neural Repair. 2010; 24:702-8.
• [26]Hofstetter CP, Holmstrom NA, Lilja JA, Schweinhardt P, Hao J, Spenger C et al.. Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome. Nat Neurosci. 2005; 8:346-53.
• [27]Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I et al.. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2011; 67:1187-94.