Stem Cell Transplantation for Traumatic Spinal Cord Injury: What Have We Learned from Previous Experience
American Journal of Bioscience and Bioengineering
Volume 3, Issue 4-1, July 2015, Pages: 34-42
Received: Jun. 20, 2015;
Accepted: Jun. 22, 2015;
Published: Jul. 6, 2015
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Elhawary S., Faculty of Medicine, Cairo University, Cairo, Egypt
Wagih A., Faculty of Medicine, Cairo University, Cairo, Egypt
Essam B., Faculty of Medicine, Cairo University, Cairo, Egypt
Tarek I., Faculty of Medicine, Cairo University, Cairo, Egypt
Aamer M., Faculty of Medicine, Cairo University, Cairo, Egypt
Ellessy R. M., Faculty of Medicine, Cairo University, Cairo, Egypt
Spinal cord injuries represent one of the most devastating illnesses that can affect the human body. Before the advent of the regenerative medicine era, it was regarded as an untreatable condition. Stem cell plasticity and translational medicine research open a new window of hope for this category of patients. Clinical trials of stem cell therapy for spinal cord injuries are now more than a decade old. However, the diversity of clinical trial design, cell type, dose and route of injection, make it extremely difficult to draw decisions from these previous experience. This review tries to collect as much evidence as we can from previous studies in order to suggest paths for future research in this setting.
Ellessy R. M.,
Stem Cell Transplantation for Traumatic Spinal Cord Injury: What Have We Learned from Previous Experience, American Journal of Bioscience and Bioengineering. Special Issue:Stem Cells for Neuro-Regeneration: Where Do We Stand.
Vol. 3, No. 4-1,
2015, pp. 34-42.
Furlan JC, Sakakibara BM, Miller WC, Krassioukov AV (2013): Global incidence and prevalence of traumatic spinal cord injury. Can J Neurol Sci.;40(4):456-64.
Lakshmipathy U, Verfaillie C (2005): Stem Cell Plasticity. Blood Rev 19(1):29-38.
Woodburry D, Schwarz EJ, Prockop DJ (2000): Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosc Res 61(4):364-370.
Zhang SCm Wermig M, Duncan ID Brustle O (2001): In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nature Biotech 19:1129-1133.
Sanchez-Ramos J, Song S, Cardozo=Pelaez F, Hazzi C, Stedeford T, Willing A, Freeman TB, Saporta S, Janssen W, Patel N, Cooper DR, Sanberg PR (2000): Adult Bone Marrow Stromal Cells Differentiate into Neural Cells in Vitro. Exp Neurol 164(2):247-256.
Mostafavi FS, Razavi S, Mardani M, Esfandiari E, Esfahani HZ and Kazemi M.(2014): Comparative Study of Microtubule-associated Protein-2 and Glial Fibrillary Acidic Proteins during Neural Induction of Human Bone Marrow Mesenchymal Stem Cells and Adipose-Derived Stem Cells. Int J Prev Med.; 5:584-95.
da Silva Meirelles L, Chagastelles PC and Nardi NB.(2006): Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci.; 119:2204-13.
Dezawa M, Takahashi I, Esaki M, Takano M and Sawada H. (2001): Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells. Eur J Neurosci.; 14:1771-6.
Kalbermatten DF, Schaakxs D, Kingham PJ and Wiberg M. (2011): Neurotrophic activity of human adipose stem cells isolated from deep and superficial layers of abdominal fat. Cell Tissue Res.; 344:251-60.
Razavi S, Razavi MR, Zarkesh Esfahani H, Kazemi M and Mostafavi FS.(2013): Comparing brain-derived neurotrophic factor and ciliary neurotrophic factor secretion of induced neurotrophic factor secreting cells from human adipose and bone marrow-derived stem cells. Dev Growth Differ.; 55:648-55.
Liao D, Gong P, Li X, Tan Z and Yuan Q.(2010) Co-culture with Schwann cells is an effective way for adipose-derived stem cells neural transdifferentiation. Arch Med Sci.; 6:145-51.
Zhang WC, Ding YJ, Cao JK, Du JX, Zhang GF and Liu YJ.(1994): Intracerebral cografting of Schwann’s cells and fetal adrenal medulla in the treatment of Parkinson’s disease. Chin Med J (Engl); 107:583-8.
Jiang CC, Xia Y, Ding ZL, Wang Y and Xu B.(2006): Effects of co-engraftment of Schwann cells with neural stem cells into rats with Parkinson disease. Chin Med J (Engl). ; 119:1030-3.
Sadan O, Shemesh N, Barzilay R, Bahat-Stromza M, Melamed E, Cohen Y and Offen D. (2008): Migration of neurotrophic factors-secreting mesenchymal stem cells toward a quinolinic acid lesion as viewed by magnetic resonance imaging. Stem Cells.; 26:2542-51.
Crigler L, Robey RC, Asawachaicharn A (2006):. Human mesenchymal stem cell subpopulations express a variety of neuroregulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol.;198:54–64.
Ma T, Gong K, Ao Q, Yan Y, Song B, Huang H, Zhang X and Gong Y. (2013): Intracerebral transplantation of adipose-derived mesenchymal stem cells alternatively activates microglia and ameliorates neuropathological deficits in Alzheimer’s disease mice. Cell Transplant.; 22 Suppl 1:S113-26.
Hu BYm Weick JPm Yu J, Ma L, Zhang Z, Thomson J and Zhang S (2010): Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. PNAS 107(9).
Swistowski A1, Peng J, Liu Q, Mali P, Rao MS, Cheng L, Zeng X.(2010): Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions. . Stem Cells. 2010 Oct;28(10):1893-904.
Paldino E1, Cenciarelli C, Giampaolo A, Milazzo L, Pescatori M, Hassan HJ, Casalbore P.(2014): Induction of dopaminergic neurons from human Wharton's jelly mesenchymal stem cell by forskolin J Cell Physiol. 2014 Feb;229(2):232-44.
Wichterle H1, Lieberam I, Porter JA, Jessell TM.(2002): Directed differentiation of embryonic stem cells into motor neurons. Cell. 2002 Aug 9;110(3):385-97.
Selvaraj V1, Jiang P, Chechneva O, Lo UG, Deng W. (2012): Differentiating human stem cells into neurons and glial cells for neural repair.Front Biosci (Landmark Ed). 2012 Jan 1;17:65-89.
Hardy SA, Maltman DJ, Przyborski SA. (2008): Mesenchymal stem cells as mediators of neural differentiation.Curr Stem Cell Res Ther. ;3:43–52.
Madrigal M, Rao KS, Riordan NH (2014): A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. J Transl Med 12:260.
Razavi S, Jahromi M, Amirpour N and Khosravizadeh Z. Effect of sertraline on proliferation and neurogenic differentiation of human adipose-derived stem cells (2014): Adv Biomed Res.; 25:97.
Radtke C, Schmitz B, Spies M, Kocsis JD and Vogt PM.(2009): Peripheral glial cell differentiation from neurospheres derived from adipose mesenchymal stem cells. Int J Dev Neurosci.; 27:817-23.
Gebler A, Zabel O, Seliger B (2012): The immunomodulatory capacity of mesenchymal stem cells. Trends in Mol Med 18(2):p128–134.
Hoogduijn MJ, Popp F, Verbeek R, Masoodi M , Nicolaou A, Baan , Dahlke M (2010): The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy. Int Immunopharmacolog 10(12):1496-1500.
Huang WH, Chang MC, Tsai KS, Hung MC, Chen HL, Hung SC. (2013): Mesenchymal stem cells promote growth and angiogenesis of tumors in mice. . Oncogene. ;32(37):4343-54.
Martins L, Martin PK, Han SW. (2014): Angiogenic properties of mesenchymal stem cells in a mouse model of limb ischemia. Methods Mol Biol.;1213:147-69
Joyce N, Annett G., Wirthlin L, Olson S, Bauer G, and Nolta JA (2010): Mesenchymal stem cells for the treatment of neurodegenerative disease Regen Med.; 5(6): 933–946.
Kramer R, Zhang Y, Gehrmann J, Gold R, Thoenen H and Wekerle H. (1995): Gene transfer through the blood-nerve barrier: NGF-engineered neuritogenic T lymphocytes attenuate experimental autoimmune neuritis. Nat Med. ; 1:1162-6.
Kim JH, Lee HJ, and Song JS (2014): Stem Cell Based Gene Therapy in Prostate Cancer
BioMed Res Int; 2014:Article ID 549136, 8 pages. Uchibori R, Tsukahara T, Ohmine K, Ozawa K. (2014): Cancer gene therapy using mesenchymal stem cells. Int J Hematol.;99(4):377-82.
Feron F, Perry C, Cochrane J, Licina P, Nowitzke A, Urquhart S, Geraghty T, Mackay-Sim A (2005): Autologous olfactory ensheathing cell transplantation in human spinal cord injury. Brain 657: 2951-2960.
Lima C, Pratas-Vital J, Escada P, Hasse-Fereira A, Capucho C, Peduzzi JD (2006): Olfactory mucosa autografts in human spinal cord injury: a pilot clinical study. J Spinal Cord Med; 29(3): 191-203.
Yoon SH, Shim YS, Park YH, Chung JK, Nam JH, Kim MO, Park HC, Park SR, Min BH, Kim EY, Choi BH, Park H, Ha Y (2007): Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase I/II clinical trial. . Stem Cells.25(8):2066-73.
Chernykh ER, Stupak VV, Muradov GM, Sizikov MY, Shevela EY, Leplina OY, Tikhonova MA, Kulagin AD, Lisukov IA, Ostanin AA, Kozlov VA (2007): Application of autologous bone marrow stem cells in the therapy of spinal cord injury patients. Bull Exp Biol Med. ;143(4):543-7.
Cristante AF, Barros-Filho TE, Tatsui N, Mendrone A, Caldas JG, Camargo A, Alexandre A, Teixeira WG, Oliveira RP, Marcon RM (2009): Stem cells in the treatment of chronic spinal cord injury: evaluation of somatosensitive evoked potentials in 39 patients. Spinal Cord. 47(10):733-8.
Abo El-Kheir W, Gabr H, Awad MR, von Wild K, and Ramadan M (2010): Autologous Mesenchymal Stem Cells for Neuro-Regeneration After Traumatic Spinal Cord Injury: A Comparison Between Bone Marrow and Peripheral Blood Populations. Am J Neuroprot and Neuroregene; 2: 1–8.
Abdelaziz OS, Marie A, Abbas M, Ibrahim M, Gabr H (2010): Feasibility, Safety, and Efficacy of Directly Transplanting Autologous Adult Bone Marrow Stem Cells in Patients With Chronic Traumatic Dorsal Cord Injury. A Pilot Clinical Study. Neurosurg Q 2010;20:216–226.
Kishk NA, Gabr H, Hamdy S, Afifi L, Abokresha N, Mahmoud H, Wafaie A and Bilal D ( 2010): Case Control Series of Intrathecal Autologous Bone Marrow Mesenchymal Stem Cell Therapy for Chronic Spinal Cord Injury. Neurorehabil Neural Repair.
El-Kheir WA, Gabr H, Awad MR, Ghannam O, Barakat Y, Farghali HA, Maadawi ZM, Ewes I, Sabaawy HE. (2013):Autologous bone marrow-derived cell therapy combined with physical therapy induces functional improvement in chronic spinal cord injury patients. Cell Transplant.
Dai G, Liu X, Zhang Z, Yang Z, Dai Y, Xu R (2013):Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. Brain Res.;1533:73-9.
Karamouzian S, Nematollahi-Mahani SN, Nakhaee N, Eskandary H.(2012): Clinical safety and primary efficacy of bone marrow mesenchymal cell transplantation in subacute spinal cord injured patients. Clin Neurol Neurosurg.;114(7):935-9.
Park JH, Kim DY, Sung IY, Choi GH, Jeon MH, Kim,K, Jeon SR 2012): ): Long-term Results of Spinal Cord Injury Therapy Using Mesenchymal Stem Cells Derived From Bone Marrow in Humans. Neurosurgery: 70(5):1238-1247.
Gabr, H.; Ghannam, O.; Awad, MR; von Wild, K.; El-Kheir, W.; Ewes, I. (2011): Autologous Mesenchymal Stem Cell Therapy for Spinal Cord Injury: Long Term Safety and Clinical Efficacy American Journal of Neuroprotection and Neuroregeneration, 3( 1):100-106(7).
Kumar AA, Kumar SR, Narayanan R, Arul K, Baskaran M.(2009): Autologous bone marrow derived mononuclear cell therapy for spinal cord injury: A phase I/II clinical safety and primary efficacy data. Exp Clin Transplant.;7(4):241-8.
Pal R, Venkataramana NK, Bansal A, Balaraju S, Jan M, Chandra R, Dixit A, Rauthan A, Murgod U, Totey S (2009): Ex vivo-expanded autologous bone marrow-derived mesenchymal stromal cells in human spinal cord injury/paraplegia: a pilot clinical study. Cytotherapy.;11(7):897-911.
Mackay-Sim A, Féron F, Cochrane J, Bassingthwaighte L, Bayliss C, Davies W, Fronek P, Gray C, Kerr G, Licina P, Nowitzke A, Perry C, Silburn PA, Urquhart S, Geraghty T.(2008): Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial. Brain.;131(Pt 9):2376-86.
Subbaiah G, Adavi V, Chelluri L, Laxman S, Ratnakar K, Gopal P, Ravindranath K(2008):Preliminary report on the safety, efficacy and functional recovery of spinal cord injury with autologous bone marrow derived mesenchymal stem cells – a clinical trial. Int J Spine Surg 5(1).
Moviglia GA, Fernandez Viña R, Brizuela JA, Saslavsky J, Vrsalovic F, Varela G, Bastos F, Farina P, Etchegaray G, Barbieri M, Martinez G, Picasso F, Schmidt Y, Brizuela P, Gaeta CA, Costanzo H, Moviglia Brandolino MT, Merino S, Pes ME, Veloso MJ, Rugilo C, Tamer I, Shuster GS.(2006): Combined protocol of cell therapy for chronic spinal cord injury. Report on the electrical and functional recovery of two patients. Cytotherapy; 8(3):202-9.
Callera F, do Nascimento RX. (2006): 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. Exp Hematol. ;34(2):130-1.