Autologous bone marrow derived mononuclear cell therapy for spinal cord injury: A phase I/II clinical safety and primary efficacy data

Experimental and Clinical Transplantation

Volumn 7, Issue 4, 2009, Pages 241-248

  Kumar, Arachimani Anand ^a   Kumar, Sankaran Raj ^a   Narayanan, Raghavachary ^a   Arul, Kanagarajan ^a   Baskaran, Mayakesavan ^a  

^a Lifeline Institute of Regenerative Medicine   (India)

Author keywords

Hematopoietic stem cells; Phase I II clinical trial; Regenerative therapy; Spinal cord injury; Stem cells

Indexed keywords

ARTICLE; AUTOLOGOUS BONE MARROW TRANSPLANTATION; BURNING SENSATION; CD34 SELECTION; CELL COUNT; CELL THERAPY; CONTROLLED STUDY; FEVER; GROUPS BY AGE; HEADACHE; HUMAN; LUMBAR PUNCTURE; MAJOR CLINICAL STUDY; MOTOR PERFORMANCE; MUSCLE SPASM; PAIN; RISK ASSESSMENT; SENSORY EVALUATION; SEX DIFFERENCE; SKIN TINGLING; SPINAL CORD INJURY; TREATMENT OUTCOME;

ADULT; ADULT STEM CELLS; ANTIGENS, CD34; BONE MARROW TRANSPLANTATION; FEMALE; HUMANS; MALE; MIDDLE AGED; MOTOR ACTIVITY; NERVE REGENERATION; PARAPLEGIA; PILOT PROJECTS; QUADRIPLEGIA; RECOVERY OF FUNCTION; SENSATION; SEVERITY OF ILLNESS INDEX; SPINAL CORD INJURIES; SPINAL PUNCTURE; STEM CELL TRANSPLANTATION; TIME FACTORS; TRANSPLANTATION, AUTOLOGOUS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 75649125329     PISSN: 13040855     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (36)

1. Barnabé-Heider F, Frisén J. Stem cells for spinal cord repair. Cell Stem Cell. 2008;3(1):16-24.
2. Parr AM, Tator CH, Keating A. Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury. Bone Marrow Transplant. 2007;40(7):609-619.
3. Alexanian AR, Maiman DJ, Kurpad SN, Gennarelli TA. In vitro and in vivo characterization of neurally modified mesenchymal stem cells induced by epigenetic modifiers and neural stem cell environment. Stem Cells Dev. 2008;17(6):1123-1130.
4. Hawryluk GW, Fehlings MG. The center of the spinal cord may be central to its repair. Cell Stem Cell. 2008;3(3):230-232.
5. Isele NB, Lee HS, Landshamer S, et al. Bone marrow stromal cells mediate protection through stimulation of PI3-K/Akt and MAPK signaling in neurons. Neurochem Int. 2007;50(1):243-250.
6. Rolls A, Shechter R, Schwartz M. The bright side of the glial scar in CNS repair. Nat Rev Neurosci. 2009;10(3):235-241.
7. Moviglia GA, Varela G, Gaeta CA, Brizuela JA, Bastos F, Saslavsky J. Autoreactive T cells induce in vitro BM mesenchymal stem cell transdifferentiation to neural stem cells. Cytotherapy. 2006;8(3):196-201.
8. Baptiste DC, Fehlings MG. Update on the treatment of spinal cord injury. Prog Brain Res. 2007;161:217-233
9. Song S, Sanchez-Ramos J. Preparation of neural progenitors from bone marrow and umbilical cord blood. Methods Mol Biol. 2008;438:123-134.
10. Song S, Song S, Zhang H, Cuevas J, Sanchez-Ramos J. Comparison of neuron-like cells derived from bone marrow stem cells to those differentiated from adult brain neural stem cells. Stem Cells Dev. 2007;16(5):747-756.
11. Vaquero J, ZuritaM. Bonemarrow stromal cells for spinal cord repair: a challenge for contemporary neurobiology. Histol Histopathol. 2009;24(1):107-116.
12. Parr AM, Kulbatski I, Wang XH, Keating A, Tator CH. Fate of transplanted adult neural stem/progenitor cells and bone marrowderived mesenchymal stromal cells in the injured adult rat spinal cord and impact on functional recovery. Surg Neurol. 2008;70(6):600-607; discussion 607.
13. Ladle DR, Pecho-Vrieseling E, Arber S. Assembly of motor circuits in the spinal cord: driven to function by genetic and experience-dependent mechanisms. Neuron. 2007;56(2):270-283.
14. Keirstead HS. Stem cells for the treatment of myelin loss. Trends Neurosci. 2005;28(12):677-683.
15. Deng YB, Liu XG, Liu ZG, Liu XL, Liu Y, Zhou GQ. Implantation of BM mesenchymal stem cells into injured spinal cord elicits de novo neurogenesis and functional recovery: evidence from a study in rhesus monkeys. Cytotherapy. 2006;8(3):210-214.
16. Syková E, Homola A, Mazanec R, et al. Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell Transplant. 2006;15(8-9):675-687.
17. Samijn JP, te Boekhorst PA, Mondria T, et al. Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis. J Neurol Neurosurg Psychiatry. 2006;77(1):46-50.
18. Cristante AF, Barros-Filho TE, Tatsui N, et al. Stem cells in the treatment of chronic spinal cord injury: evaluation of somatosensitive evoked potentials in 39 patients. Spinal Cord. 2009;31.
19. Deda H, Inci MC, Kürekçi AE, et al. Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up. Cytotherapy. 2009;11(1):18-25.
20. Chernykh ER, Stupak VV, Muradov GM, et al. Application of autologous bonemarrowstemcells in the therapy of spinal cord injury patients. Bull Exp Biol Med. 2007;143(4):543-547.
21. Moviglia GA, Varela G, Brizuela JA, et al. Case report on the clinical results of a combined cellular therapy for chronic spinal cord injured patients. Spinal Cord. 2009;47(6):499-503.
22. Koda M, Okada S, Nakayama T, et al. Hematopoietic stem cell and marrow stromal cell for spinal cord injury in mice. Neuroreport. 2005;16(16):1763-1767.
23. Sigurjonsson OE, Perreault MC, Egeland T, Glover JC. Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord. Proc Natl Acad Sci U S A. 2005;102(14):5227-5232.
24. Carvalho KA, Cunha RC, Vialle EN, et al. Functional outcome of bone marrow stem cells (CD45(+)/CD34(-)) after cell therapy in acute spinal cord injury: in exercise training and in sedentary rats. Transplant Proc. 2008;40(3):847-849.
25. Hunt DP, Irvine KA, Webber DJ, Compston DA, Blakemore WF, Chandran S. Effects of direct transplantation of multipotent mesenchymal stromal/stem cells into the demyelinated spinal cord. Cell Transplant. 2008;17(7):865-873.
26. Paul C, Samdani AF, Betz RR, Fischer I, Neuhuber B. Grafting of human bone marrow stromal cells into spinal cord injury: a comparison of delivery methods. Spine (Phila Pa 1976). 2009;34(4):328-334.
27. Bakshi A, Barshinger AL, Swanger SA, et al. Lumbar puncture delivery of bonemarrowstromal cells in spinal cord contusion: a novelmethod for minimally invasive cell transplantation. J Neurotrauma. 2006;23(1):55-65.
28. Vercelli A,Mereuta OM, Garbossa D, et al. Humanmesenchymal stem cell transplantation extends survival, improvesmotor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis. Neurobiol Dis. 2008;31(3):395-405.
29. 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(3):461-466.
30. Callera F, do Nascimento RX. Delivery of autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique in patientswith spinal cord injury: a preliminary safety study. Exp Hematol. 2006;34(2):130-131.
31. Yang Q, Mu J, Li Q, et al. A simple and efficient method for deriving neurospheres from bone marrow stromal cells. Biochem Biophys Res Commun. 2008;372(4):520-4.
32. Wang FW, Jia DY, Du ZH, et al. Roles of activated astrocytes in bone marrow stromal cell proliferation and differentiation. Neuroscience. 2009;160:319-329.
33. Khoo ML, Shen B, Tao H, Ma DD. Long-term serial passage and neuronal differentiation capability of human bone marrow mesenchymal stem cells. Stem Cells Dev. 2008;17(5):883-896.
34. Abouelfetouh A, Kondoh T, Ehara K, Kohmura E. Morphological differentiation of bonemarrowstromal cells into neuron-like cells after co-culture with hippocampal slice. Brain Res. 2004;1029:114-119.
35. Ankeny DP, McTigue DM, Jakeman LB. Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp Neurol. 2004;190(1):17-31.
36. Croft AP, Przyborski SA. Mesenchymal stem cells expressing neural antigens instruct a neurogenic cell fate on neural stem cells. Exp Neurol. 2009;216(2):329-341.