Promise of Autologous Bone Marrow Stem Cell Transplantation to Patients with Spinal Cord Injury-Current Status
Due to rapid industrialization, population raise and development of real estate business results to build of enormous constructions, which leads to the injuries of spinal cord. The burden of spinal cord injury induced limb paralysis increasing every year in India. Increasing vehicular traffic has caused numerous road traffic accidents. Spinal cord injury (SCI) affects all aspects of a patient’s life, including the physical, behavioral, psychological and social functioning.  Spinal cord injuries could not be treated effectively with the existing treatment modalities. In view of the above, there is definitely an urgent need for finding different methods of treatment for these patients who cannot undergo established modalities of treatment or these have been tried unsuccessfully. Since a large number of these patients will loose their productive life and at the prime of their lives one such alternate therapy, which seems to offer some promise, is “stem cell” therapy, which has been well studied and published in prestigious journals. Current review discuss the safety and therapeutic efficacy of autologous human bone marrow cell (BMC) transplantation and the administration of granulocyte macrophage-colony stimulating factor (GM-CSF).
Mahaboob Vali Shaik,
Promise of Autologous Bone Marrow Stem Cell Transplantation to Patients with Spinal Cord Injury-Current Status, Clinical Neurology and Neuroscience.
Vol. 1, No. 4,
2017, pp. 84-95.
North NT. The psychological effects of spinal cord injury: a review. Spinal Cord. 1999 Oct; 37 (10): 671-9.
Kraus JF, Franti CE, Riggins RS, Richards D, Borhani NO. Incidence of traumatic spinal cord lesions. J Chronic Dis. 1975 Oct; 28 (9): 471-92.
Maynard FM, Jr., Bracken MB, Creasey G, Ditunno JF, Jr., Donovan WH, Ducker TB, et al. International Standards for Neurological and Functional Classification of Spinal Cord Injury. American Spinal Injury Association. Spinal Cord. 1997 May; 35 (5): 266-74.
Cripps RA, Lee BB, Wing P, Weerts E, Mackay J, Brown D. A global map for traumatic spinal cord injury epidemiology: towards a living data repository for injury prevention. Spinal Cord. 2011 Apr; 49 (4): 493-501.
Wyndaele M, Wyndaele JJ. Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal Cord. 2006 Sep; 44 (9): 523-9.
van den Berg ME, Castellote JM, Mahillo-Fernandez I, de Pedro-Cuesta J. Incidence of spinal cord injury worldwide: a systematic review. Neuroepidemiology. 2010; 34 (3): 184-92; discussion 92.
Chiu WT, Lin HC, Lam C, Chu SF, Chiang YH, Tsai SH. Review paper: epidemiology of traumatic spinal cord injury: comparisons between developed and developing countries. Asia Pac J Public Health. 2010 Jan; 22 (1): 9-18.
Ackery A, Tator C, Krassioukov A. A global perspective on spinal cord injury epidemiology. J Neurotrauma. 2004 Oct; 21 (10): 1355-70.
DeVivo MJ, Chen Y. Trends in new injuries, prevalent cases, and aging with spinal cord injury. Arch Phys Med Rehabil. 2011 Mar; 92 (3): 332-8.
Dryden DM, Saunders LD, Rowe BH, May LA, Yiannakoulias N, Svenson LW, et al. The epidemiology of traumatic spinal cord injury in Alberta, Canada. Can J Neurol Sci. 2003 May; 30 (2): 113-21.
Razdan S, Kaul RL, Motta A, Kaul S, Bhatt RK. Prevalence and pattern of major neurological disorders in rural Kashmir (India) in 1986. Neuroepidemiology. 1994; 13 (3): 113-9.
Singh R, Rohilla R, Siwach R, Dhankar S, Kaur K. Understanding Psycho-Social Issues in Persons with Spinal Cord Injury and Impact of Remedial Measures. International Journal of Psychosocial Rehabilitation Vol 16 (1) 104. 2012; 111.
Marino RJ, Ditunno JF, Jr., Donovan WH, Maynard F, Jr. Neurologic recovery after traumatic spinal cord injury: data from the Model Spinal Cord Injury Systems. Arch Phys Med Rehabil. 1999 Nov; 80 (11): 1391-6.
Rowland JW, Hawryluk GW, Kwon B, Fehlings MG. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg Focus. 2008; 25 (5): E2.
Beattie MS, Farooqui AA, Bresnahan JC. Review of current evidence for apoptosis after spinal cord injury. J Neurotrauma. 2000 Oct; 17 (10): 915-25.
Strauss DJ, Devivo MJ, Paculdo DR, Shavelle RM. Trends in life expectancy after spinal cord injury. Arch Phys Med Rehabil. 2006 Aug; 87 (8): 1079-85.
Geisler WO, Jousse AT, Wynne-Jones M, Breithaupt D. Survival in traumatic spinal cord injury. Paraplegia. 1983 Dec; 21 (6): 364-73.
Soden RJ, Walsh J, Middleton JW, Craven ML, Rutkowski SB, Yeo JD. Causes of death after spinal cord injury. Spinal Cord. 2000 Oct; 38 (10): 604-10.
Hagen EM, Eide GE, Rekand T, Gilhus NE, Gronning M. A 50-year follow-up of the incidence of traumatic spinal cord injuries in Western Norway. Spinal Cord. 2010 Apr; 48 (4): 313-8.
Burke DA, Linden RD, Zhang YP, Maiste AC, Shields CB. Incidence rates and populations at risk for spinal cord injury: A regional study. Spinal Cord. 2001 May; 39 (5): 274-8.
Hartkopp A, Bronnum-Hansen H, Seidenschnur AM, Biering-Sorensen F. Suicide in a spinal cord injured population: its relation to functional status. Arch Phys Med Rehabil. 1998 Nov; 79 (11): 1356-61.
Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature. 2000 Jan 27; 403 (6768): 434-9.
Cai D, Qiu J, Cao Z, McAtee M, Bregman BS, Filbin MT. Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J Neurosci. 2001 Jul 1; 21 (13): 4731-9.
Fitch MT, Doller C, Combs CK, Landreth GE, Silver J. Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. J Neurosci. 1999 Oct 1; 19 (19): 8182-98.
Davies SJ, Fitch MT, Memberg SP, Hall AK, Raisman G, Silver J. Regeneration of adult axons in white matter tracts of the central nervous system. Nature. 1997 Dec 18-25; 390 (6661): 680-3.
Neumann S, Woolf CJ. Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron. 1999 May; 23 (1): 83-91.
Blight AR. Cellular morphology of chronic spinal cord injury in the cat: analysis of myelinated axons by line-sampling. Neuroscience. 1983 Oct; 10 (2): 521-43.
Cheng H, Cao Y, Olson L. Spinal cord repair in adult paraplegic rats: partial restoration of hind limb function. Science. 1996 Jul 26; 273 (5274): 510-3.
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 Dec; 5 (12): 1410-2.
Imaizumi T, Lankford KL, Burton WV, Fodor WL, Kocsis JD. Xenotransplantation of transgenic pig olfactory ensheathing cells promotes axonal regeneration in rat spinal cord. Nat Biotechnol. 2000 Sep; 18 (9): 949-53.
Bregman BS, Kunkel-Bagden E, Schnell L, Dai HN, Gao D, Schwab ME. Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors. Nature. 1995 Nov 30; 378 (6556): 498-501.
Liu S, Qu Y, Stewart TJ, Howard MJ, Chakrabortty S, Holekamp TF, et al. Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation. Proc Natl Acad Sci U S A. 2000 May 23; 97 (11): 6126-31.
Ramon-Cueto A, Cordero MI, Santos-Benito FF, Avila J. Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron. 2000 Feb; 25 (2): 425-35.
Eglitis MA, Mezey E. Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci U S A. 1997 Apr 15; 94 (8): 4080-5.
Teng YD, Mocchetti I, Taveira-DaSilva AM, Gillis RA, Wrathall JR. Basic fibroblast growth factor increases long-term survival of spinal motor neurons and improves respiratory function after experimental spinal cord injury. J Neurosci. 1999 Aug 15; 19 (16): 7037-47.
Xu XM, Guenard V, Kleitman N, Aebischer P, Bunge MB. A combination of BDNF and NT-3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat thoracic spinal cord. Exp Neurol. 1995 Aug; 134 (2): 261-72.
Grill R, Murai K, Blesch A, Gage FH, Tuszynski MH. Cellular delivery of neurotrophin-3 promotes corticospinal axonal growth and partial functional recovery after spinal cord injury. J Neurosci. 1997 Jul 15; 17 (14): 5560-72.
Diener PS, Bregman BS. Fetal spinal cord transplants support the development of target reaching and coordinated postural adjustments after neonatal cervical spinal cord injury. J Neurosci. 1998 Jan 15; 18 (2): 763-78.
Gautier SE, Oudega M, Fragoso M, Chapon P, Plant GW, Bunge MB, et al. Poly (alpha-hydroxyacids) for application in the spinal cord: resorbability and biocompatibility with adult rat Schwann cells and spinal cord. J Biomed Mater Res. 1998 Dec 15; 42 (4): 642-54.
Koshizuka S, Okada S, Okawa A, Koda M, Murasawa M, Hashimoto M, et al. Transplanted hematopoietic stem cells from bone marrow differentiate into neural lineage cells and promote functional recovery after spinal cord injury in mice. J Neuropathol Exp Neurol. 2004 Jan; 63 (1): 64-72.
Snyder EY, Park KI, Flax JD, Liu S, Rosario CM, Yandava BD, et al. Potential of neural "stem-like" cells for gene therapy and repair of the degenerating central nervous system. Adv Neurol. 1997; 72: 121-32.
Goto S, Yamada K, Yoshikawa M, Okamura A, Ushio Y. GABA receptor agonist promotes reformation of the striatonigral pathway by transplant derived from fetal striatal primordia in the lesioned striatum. Exp Neurol. 1997 Oct; 147 (2): 503-9.
Gage FH. Stem cells of the central nervous system. Curr Opin Neurobiol. 1998 Oct; 8 (5): 671-6.
Ankeny DP, Mc Tigue DM, Jakeman LB. Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp Neurol. 2004 Nov; 190 (1): 17-31.
Kempermann G, Gage FH. Closer to neurogenesis in adult humans. Nat Med. 1998 May; 4 (5): 555-7.
Bonifer C, Faust N, Geiger H, Muller AM. Developmental changes in the differentiation capacity of haematopoietic stem cells. Immunol Today. 1998 May; 19 (5): 236-41.
Prewitt CM, Niesman IR, Kane CJ, Houle JD. Activated macrophage/microglial cells can promote the regeneration of sensory axons into the injured spinal cord. Exp Neurol. 1997 Dec; 148 (2): 433-43.
Knoller N, Auerbach G, Fulga V, Zelig G, Attias J, Bakimer R, et al. Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine. 2005 Sep; 3 (3): 173-81.
Beattie MS. Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med. 2004 Dec; 10 (12): 580-3.
Gonzalez R, Glaser J, Liu MT, Lane TE, Keirstead HS. Reducing inflammation decreases secondary degeneration and functional deficit after spinal cord injury. Exp Neurol. 2003 Nov; 184 (1): 456-63.
Beresford JN, Bennett JH, Devlin C, Leboy PS, Owen ME. Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J Cell Sci. 1992 Jun; 102 (Pt 2): 341-51.
Lennon DP, Haynesworth SE, Young RG, Dennis JE, Caplan AI. A chemically defined medium supports in vitro proliferation and maintains the osteochondral potential of rat marrow-derived mesenchymal stem cells. Exp Cell Res. 1995 Jul; 219 (1): 211-22.
Wakitani S, Saito T, Caplan AI. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve. 1995 Dec; 18 (12): 1417-26.
Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res. 2000 Aug 15; 61 (4): 364-70.
Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol. 2000 Aug; 164 (2): 247-56.
Deng W, Obrocka M, Fischer I, Prockop DJ. In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP. Biochem Biophys Res Commun. 2001 Mar 23; 282 (1): 148-52.
Castro-Malaspina H, Gay RE, Resnick G, Kapoor N, Meyers P, Chiarieri D, et al. Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny. Blood. 1980 Aug; 56 (2): 289-301.
Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci U S A. 1999 Sep 14; 96 (19): 10711-6.
Azizi SA, Stokes D, Augelli BJ, Di Girolamo C, Prockop DJ. Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats--similarities to astrocyte grafts. Proc Natl Acad Sci U S A. 1998 Mar 31; 95 (7): 3908-13.
Chopp M, Zhang XH, Li Y, Wang L, Chen J, Lu D, et al. Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation. Neuroreport. 2000 Sep 11; 11 (13): 3001-5.
Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, et al. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med. 1999 Mar; 5 (3): 309-13.
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 Feb 19; 99 (4): 2199-204.
Clark BR, Keating A. Biology of bone marrow stroma. Ann N Y Acad Sci. 1995 Dec 29; 770: 70-8.
Ramer LM, Au E, Richter MW, Liu J, Tetzlaff W, Roskams AJ. Peripheral olfactory ensheathing cells reduce scar and cavity formation and promote regeneration after spinal cord injury. J Comp Neurol. 2004 May 17; 473 (1): 1-15.
Pearse DD, Marcillo AE, Oudega M, Lynch MP, Wood PM, Bunge MB. Transplantation of Schwann cells and olfactory ensheathing glia after spinal cord injury: does pretreatment with methylprednisolone and interleukin-10 enhance recovery? J Neurotrauma. 2004 Sep; 21 (9): 1223-39.
Ogawa Y, Sawamoto K, Miyata T, Miyao S, Watanabe M, Nakamura M, et al. Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats. J Neurosci Res. 2002 Sep 15; 69 (6): 925-33.
Munoz-Elias G, Woodbury D, Black IB. Marrow stromal cells, mitosis, and neuronal differentiation: stem cell and precursor functions. Stem Cells. 2003; 21 (4): 437-48.
Akiyama Y, Radtke C, Kocsis JD. Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells. J Neurosci. 2002 Aug 1; 22 (15): 6623-30.
Kawada H, Takizawa S, Takanashi T, Morita Y, Fujita J, Fukuda K, et al. Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells. Circulation. 2006 Feb 7; 113 (5): 701-10.
Chen Q, Long Y, Yuan X, Zou L, Sun J, Chen S, et al. Protective effects of bone marrow stromal cell transplantation in injured rodent brain: synthesis of neurotrophic factors. J Neurosci Res. 2005 Jun 1; 80 (5): 611-9.
Huang H, Chen L, Wang H, Xi H, Gou C, Zhang J, et al. Safety of fetal olfactory ensheathing cell transplantation in patients with chronic spinal cord injury. A 38-month follow-up with MRI. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2006 Apr; 20 (4): 439-43.
Park HC, Shim YS, Ha Y, Yoon SH, Park SR, Choi BH, et al. Treatment of complete spinal cord injury patients by autologous bone marrow cell transplantation and administration of granulocyte-macrophage colony stimulating factor. Tissue Eng. 2005 May-Jun; 11 (5-6): 913-22.
Grasso G, Sfacteria A, Passalacqua M, Morabito A, Buemi M, Macri B, et al. Erythropoietin and erythropoietin receptor expression after experimental spinal cord injury encourages therapy by exogenous erythropoietin. Neurosurgery. 2005 Apr; 56 (4): 821-7; discussion -7.
Gibson CL, Jones NC, Prior MJ, Bath PM, Murphy SP. G-CSF suppresses edema formation and reduces interleukin-1 beta expression after cerebral ischemia in mice. J Neuropathol Exp Neurol. 2005 Sep; 64 (9): 763-9.
Brines M, Grasso G, Fiordaliso F, Sfacteria A, Ghezzi P, Fratelli M, et al. Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc Natl Acad Sci U S A. 2004 Oct 12; 101 (41): 14907-12.
Bouhy D, Malgrange B, Multon S, Poirrier AL, Scholtes F, Schoenen J, et al. Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery in paraplegic rats via an increased BDNF expression by endogenous macrophages. FASEB J. 2006 Jun; 20 (8): 1239-41.
Hofstetter CP, Schwarz E, 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. Proceedings of the National Academy of Sciences. 2002; 99 (4): 2199-204.
Chopp M, Zhang XH, Li Y, Wang L, Chen J, Lu D, et al. Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation. Neuroreport. 2000; 11 (13): 3001-5.
Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis. Nature. 2004 Nov 18; 432 (7015): 324-31.
Luck R, Klempnauer J, Steiniger B. Simultaneous occurrence of graft-versus-host and host-versus-graft reactions after allogenic MHC class II disparate small bowel transplantation in immunocompetent rats. Transplant Proc. 1991 Feb; 23 (1 Pt 1): 677-8.
Ha Y, Kim YS, Cho JM, Yoon SH, Park SR, Yoon DH, et al. Role of granulocyte-macrophage colony-stimulating factor in preventing apoptosis and improving functional outcome in experimental spinal cord contusion injury. J Neurosurg Spine. 2005 Jan; 2 (1): 55-61.
Wu S, Suzuki Y, Ejiri Y, Noda T, Bai H, Kitada M, et al. Bone marrow stromal cells enhance differentiation of cocultured neurosphere cells and promote regeneration of injured spinal cord. Journal of neuroscience research. 2003; 72 (3): 343-51.
Neuhuber B, Himes BT, Shumsky JS, Gallo G, Fischer I. Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations. Brain research. 2005; 1035 (1): 73-85.
Sigurjonsson OE, Perreault M-C, Egeland T, Glover JC. Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102 (14): 5227-32.
Čížková D, Rosocha J, Vanický I, Jergová S, Čížek M. Transplants of human mesenchymal stem cells improve functional recovery after spinal cord injury in the rat. Cellular and molecular neurobiology. 2006; 26 (7-8): 1165-78.
Zurita M, Vaquero J. Functional recovery in chronic paraplegia after bone marrow stromal cells transplantation. Neuroreport. 2004; 15 (7): 1105-8.
Vaquero J, Zurita M, Oya S, Santos M. Cell therapy using bone marrow stromal cells in chronic paraplegic rats: systemic or local administration? Neuroscience letters. 2006; 398 (1): 129-34.
Koda M, Nishio Y, Kamada T, Someya Y, Okawa A, Mori C, et al. Granulocyte colony-stimulating factor (G-CSF) mobilizes bone marrow-derived cells into injured spinal cord and promotes functional recovery after compression-induced spinal cord injury in mice. Brain research. 2007; 1149: 223-31.
Park HC, Shim YS, Ha Y, Yoon SH, Park SR, Choi BH, et al. Treatment of complete spinal cord injury patients by autologous bone marrow cell transplantation and administration of granulocyte-macrophage colony stimulating factor. Tissue Engineering. 2005; 11 (5-6): 913-22.
Callera F, do Nascimento RX. Delivery of autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique in patients with spinal cord injury: a preliminary safety study. Experimental hematology. 2006; 34 (2): 130-1.
Syková E, Homola A, Mazanec R, Lachmann H, Langkramer Konrádová Š, Kobylka P, et al. Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell transplantation. 2006; 15 (8-1): 675-87.
Deda H, Inci M, Kürekçi A, Kayıhan K, Özgün E, Üstünsoy G, et al. Treatment of chronic spinal cord injured patients with autologous bone marrow-derived hematopoietic stem cell transplantation: 1-year follow-up. Cytotherapy. 2008; 10 (6): 565-74.
Geffner L, Santacruz P, Izurieta M, Flor L, Maldonado B, Auad A, et al. Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies. Cell transplantation. 2008; 17 (12): 1277-93.