Skip to main content
SpringerLink
Log in
Book cover

Perspectives of Stem Cells pp 271–284Cite as

Dual Roles of Mesenchymal Stem Cells in Spinal Cord Injury: Cell Replacement Therapy and as a Model System to Understand Axonal Repair

  • Chapter
  • First Online:

  • 684 Accesses

Abstract

Mesenchymal stem cells (MSC) are pluripotent cells that differentiate into cells of mesodermal origin and transdifferentiate into ectodermal and endodermal cell types. MSC can transdifferentiate with high efficiency to functional neurons, microglia and oligodendrocytes. MSC and neurons can respond to environmental cues such as cytokines, which also affect the development to neural cells. Since cytokines and other inflammatory mediators are also expected at sites of spinal cord injury (SCI), simple implantation of MSC and/or their differentiated cells might be premature unless the basic science precedes translational science. This is particularly true since an individual’s immune response might be unique. Similar argument could be made for embryonic stem cells (ESC). The unstable behavior of ESC to form tumors, as well as rapid generation of mixed cell types makes MSC desirable stem cells for translational science. This review discusses varied interdisciplinary approaches by which MSC can be applied to SCI repair, including bioengineering approach. The mechanism by which microenvironmental factors such as inflammatory mediators can affect stem cell therapies is also discussed. In addition to the potential of direct application of stem cells or their differentiated cells, MSC can be used as models to understand axonal repair, which could lead to the development of new drugs for SCI. The model could test novel factors to repair neurons. Any identified factor could be delivered directly or by gene therapy. The co-culture method is significant to long-term investigation for rapid screening of compounds, with simultaneous understanding of repair mechanisms of axotomized neurons. The model could be translated in parallel with other stem cell therapies for SCI repair. We also discuss the potential of stem cell therapies for other neurodegenerative diseases.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

BDNF:

brain-derived neurotrophic factor

ESC:

embryonic stem cells

HPC:

hematopoietic progenitor cell

IFN-γ:

interferon-γ

IL-6:

interlekin-6

IL-1α:

interleukin-1α

LIF:

leukemia inhibitory factor

MEM:

microelectricomechanical systems

MSC:

mesenchymal stem cells

NEM:

nanoelectromechanical systems

NGF:

nerve growth factor

NSC:

neural stem cell(s)

NT-3:

neurotrophin-3

PNS:

peripheral nervous system

PEG:

poly-ethylene glycol

PGA:

polyglycolic acid

PLA:

polylactic acid

SCI:

spinal cord injury

STAT3:

signal transducer and activator of transcription

TGF-β1:

transforming growth factor β1

TNF-α:

tumor necrosis factor-α

References

  • Allan SM, Tyrrell PJ, Rothwell NJ (2005) Interleukin-1 and neuronal injury. Nat Rev Immunol 5:629–640.

    CAS  PubMed  Google Scholar 

  • Arinzeh TL, Tran T, Mcalary J, Daculsi G (2005) A comparative study of biphasic calcium phosphate ceramics for human mesenchymal stem cell-induced bone formation. Biomaterials 26:3631–3638.

    CAS  PubMed  Google Scholar 

  • Azari MF, Profyris C, Zang DW, Petratos S, Cheema SS (2005) Induction of endogenous neural precursors in mouse models of spinal cord injury and disease. Eur J Neurol 12: 638–648.

    CAS  PubMed  Google Scholar 

  • Bagby GC (1989) Interleukin-1 and hematopoiesis. Blood Rev 3:152–161.

    PubMed  Google Scholar 

  • Barnabé-Heider F, Frisén J (2008) Stem cells for spinal cord repair. Cell Stem Cell 3:16–24.

    PubMed  Google Scholar 

  • Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19(3):180–192.

    CAS  PubMed  Google Scholar 

  • Bieback K, Kern S, Klüter H, Eichler H (2004) Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 22:625–634.

    PubMed  Google Scholar 

  • Blanc KL, Pittenger MF (2005) Mesenchymal stem cells: progress toward promise. Cytotherapy 7:36–45.

    PubMed  Google Scholar 

  • Blesch A, Uy HS, Grill RJ, Cheng JG, Patterson PH, Tuszynski MH (1999) Leukemia inhibitory factor augments neurotrophin expression and corticospinal axon growth after adult CNS injury. J Neurosci 19:3556–3566.

    CAS  PubMed  Google Scholar 

  • Bonni A, Sun Y, Nadal-Vicens M, Bhatt A, Frank DA, Rozovsky I, Stahl N, Yancopoulos GD, Greenberg ME (1997) Regulation of gliogenesis in the central nervous system by the JAK/STAT signaling pathway. Science 278:477–483.

    CAS  PubMed  Google Scholar 

  • Bueno FR, Shah SB (2008) Implications of tensile loading for the tissue engineering of nerves. Tissue Eng Part B Rev 14:219–233.

    PubMed  Google Scholar 

  • Bunge MB (2008) Novel combination strategies to repair the injured mammalian spinal cord. J Spinal Cord Med 31:262–269.

    PubMed  Google Scholar 

  • Butzkueven H, Zhang JG, Soilu-Hanninen M, Hochrein H, Chionh F, Shipham KA, Emery B, Turnley AM, Petratos S, Ernst M, Bartlett PF, Kilpatrick TJ (2002) LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival. Nat Med 8: 613–619.

    CAS  PubMed  Google Scholar 

  • Campenot RB (1977) Local control of neurite development of nerve growth factor. Proc Natl Acad Sci U S A 74: 4516–4519.

    CAS  PubMed  Google Scholar 

  • Caplan AI (1994) The mesengenic process. Clin Plast Surg 21:429–435.

    CAS  PubMed  Google Scholar 

  • Carlos TM, Harlan JM (1994) Leukocyte-endothelial adhesion molecules. Blood 84:2068–2101.

    CAS  PubMed  Google Scholar 

  • Castillo M, Liu K, Bonilla LM, Rameshwar P (2007) The immune properties of mesenchymal stem cells. Intl J Biomed Sci 3:100.

    Google Scholar 

  • Chan JL, Tang KC, Patel AP, Bonilla LM, Pierobon N, Ponzio NM, Rameshwar P (2006) Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood 107: 4817–4824.

    CAS  PubMed  Google Scholar 

  • Chi LY, Yu J, Zhu H, Li XG, Zhu SG, Kindy MS (2008) The dual role of tumor necrosis factor-alpha in the pathophysiology of spinal cord injury. Neurosci Lett 438:174–179.

    CAS  PubMed  Google Scholar 

  • Chiba S, Lee YM, Zhou W, Freed CR (2008) Noggin enhances dopamine neuron production from human embryonic stem cells and improves behavioral outcome after transplantation into Parkinsonian rats. Stem Cells 26:2810–2820.

    CAS  PubMed  Google Scholar 

  • Cho SR, Yang MS, Yim SH, Park JH, Lee JE, Eom YW, Jang IK, Kim HE, Park JS, Kim HO, Lee BH, Park CI, Kim YJ (2008) Neurally induced umbilical cord blood cells modestly repair injured spinal cords. Neuroreport 19:1259–1263.

    PubMed  Google Scholar 

  • Cizkova D, Rosocha J, Vanicky I, Jergova S, Cizek M (2006) Transplants of human mesenchymal stem cells improve functional recovery after spinal cord injury in the rat. Cell Mol Neurobiol 26:1167–1180.

    PubMed  Google Scholar 

  • Cui L, Jiang J, Wei L, Zhou X, Fraser JL, Snider BJ, Yu SP (2008) Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats. Stem Cells 26:1356–1365.

    CAS  PubMed  Google Scholar 

  • Cummings BJ, Uchida N, Tamaki SJ, Salazar DL, Hooshmand M, Summers R (2005) Human neural stem cells differentiate and promote locomoter recovery in spinal cord-injured mice. Proc Natl Acad Sci U S A 102:14069–14074.

    CAS  PubMed  Google Scholar 

  • Deda H, Inci MC, Kurekci AE, Kayihan K, Ozgun E, Ustunsoy GE, Kocabay S (2008) Treatment of chronic spinal cord injured patients with autologous bone marrow-derived hematopoietic stem cell transplantation: 1-year follow-up. Cytotherapy 10:565–574.

    Google Scholar 

  • Deng J, Petersen BE, Steindler DA, Jorgensen ML, Laywell ED (2006) Mesenchymal stem cells spontaneously express neural proteins in culture and are neurogenic after transplantation. Stem Cells 24:1054–1064.

    CAS  PubMed  Google Scholar 

  • Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87:2095–2147.

    CAS  PubMed  Google Scholar 

  • Dinarello CA (2005) Blocking IL-1 in systemic inflammation. J Exp Med 201:1355–1359.

    CAS  PubMed  Google Scholar 

  • Divani AA, Hussain MS, Magal E, Heary RF, Qureshi AI (2007) The use of stem cells' hematopoietic stimulating factors therapy following spinal cord injury. Ann Biomed Eng 35:1647–1656.

    PubMed  Google Scholar 

  • Downing JR (2004) TGF-β signaling, tumor suppression, and acute lymphoblastic leukemia. N Engl J Med 351(6):528.

    CAS  PubMed  Google Scholar 

  • Ducker TB, Hamit HF (1969) Experimental treatments of acute spinal cord injury. J Neurosurg 30:693–697.

    CAS  PubMed  Google Scholar 

  • Ducker TB, Zeidman SM (1994) Spinal cord injury. Role of steroid therapy. Spine 19:2281–2287.

    CAS  PubMed  Google Scholar 

  • Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126:677–689.

    CAS  PubMed  Google Scholar 

  • Fujiwara T, Kubo T, Koyama Y, Tomita K, Yano K, Tohyama M, Hosokawa K (2008) mRNA expression changes of slit proteins following peripheral nerve injury in the rat model. J Chem Neuroanat 36:170–176.

    CAS  PubMed  Google Scholar 

  • Gadient RA, Otten UH (1997) Interleukin-6 (IL-6) – a molecule with both beneficial and destructive potentials. Prog Neurobiol 52:379–390.

    CAS  PubMed  Google Scholar 

  • Gao J, Coggeshall RE, Chung JM, Wang J, Wu P (2007) Functional motoneurons develop from human neural stem cell transplants in adult rats. Neuroreport 18:565–569.

    PubMed  Google Scholar 

  • Gearing DP, Gough NM, King JA, Hilton DJ, Nicola NA, Simpson RJ, Nice EC, Kelso A, Metcalf D (1987) Molecular cloning and expression of cDNA encoding a murine myeloid leukaemia inhibitory factor (LIF). EMBO J 6: 3995–4002.

    CAS  PubMed  Google Scholar 

  • Golestaneh N, Mishra B (2005) TGF-beta, neuronal stem cells and glioblastoma. Oncogene 24:5722–5730.

    CAS  PubMed  Google Scholar 

  • Greco SJ, Rameshwar P (2007) Enhancing effect of IL-1alpha on neurogenesis from adult human mesenchymal stem cells: implication for inflammatory mediators in regenerative medicine. J Immunol 179:3342–3350.

    CAS  PubMed  Google Scholar 

  • Greco SJ, Zhou C, Ye JH, Rameshwar P (2007) An interdisciplinary approach and characterization of neuronal cells transdifferentiated from human mesenchymal stem cells. Stem Cells Dev 16:811–826.

    CAS  PubMed  Google Scholar 

  • Hardy SA, Maltman DJ, Przyborski SA (2008) Mesenchymal stem cells as mediators of neural differentiation. Curr Stem Cell Res Ther 3:43–52.

    CAS  PubMed  Google Scholar 

  • Harris DT (2008) Cord blood stem cells: a review of potential neurological applications. Stem Cell Rev 4:269–274.

    PubMed  Google Scholar 

  • Hayashi M, Ueyama T, Nemoto K, Tamaki T, Senba E (2000) Sequential mRNA expression for immediate early genes, cytokines, and neurotrophins in spinal cord injury. J Neurotrauma 17:203–218.

    CAS  PubMed  Google Scholar 

  • Hernandez LA, Grisham MB, Twohig B, Arfors KE, Harlan JM, Granger DN (1987) Role of neutrophils in ischemia-reperfusion-induced microvascular injury. Am J Physiol 253:H699–H703.

    CAS  PubMed  Google Scholar 

  • Himes BT, Neuhuber B, Coleman C, Kushner R, Swanger SA, Kopen GC (2006) Recovery of function following grafting of human bone marrow-derived stromal cells into the injured spinal cord. Neurorehabil Neural Repair 20: 278–296.

    PubMed  Google Scholar 

  • Johansson S, Price J, Modo M (2008) Effect of inflammatory cytokines on MHC expression and differentiation of human neural stem/progenitor cells. Stem Cells 26:2444–2454.

    CAS  PubMed  Google Scholar 

  • Kang MK, Kang SK (2008) Interleukin-6 induces proliferation in adult spinal cord-derived neural progenitors via the JAK2/STAT3 pathway with EGF-induced MAPK phosphorylation. Cell Prolif 41:377–392.

    CAS  PubMed  Google Scholar 

  • Kazemnejad S, Allameh A, Soleimani M, Gharehbaghian A, Mohammadi Y, Amirizadeh N, Jazayery M (2008) Biochemical and molecular characterization of hepatocyte-like cells derived from human bone marrow mesenchymal stem cells on a novel three-dimensional biocompatible nanofibrous scaffold. J Gastroenterol Hepatol 24:278–287.

    PubMed  Google Scholar 

  • Kim SJ, Letterio J (2003) Transforming growth factor-beta signaling in normal and malignant hematopoiesis. Leukemia 17:1731–1737.

    CAS  PubMed  Google Scholar 

  • Kurek JB, Bennett TM, Bower JJ, Muldoon CM, Austin L (1998a) Leukaemia inhibitor factor (LIF) production in a mouse model of spinal trauma. Neurosci Lett 249:1–4.

    CAS  PubMed  Google Scholar 

  • Kurek JB, Radford AJ, Crump DE, Bower JJ, Feeney SJ, Austin L, Byrne E (1998b) LIF (AM424), a promising growth factor for the treatment of ALS. J Neurol Sci 160:S106–S113.

    CAS  PubMed  Google Scholar 

  • Kwon BK, Tetzlaff W, Grauer JN, Beiner J, Vaccaro AR (2004) Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J 4:451–464.

    PubMed  Google Scholar 

  • LaPlaca MC, Simon CM, Prado GR, Cullen DK (2007) CNS injury biomechanics and experimental models. Prog Brain Res 161:13–26.

    CAS  PubMed  Google Scholar 

  • Lange KW, Mecklinger L, Walitza S, Becker G, Gerlach M, Naumann M, Tucha O (2006) Brain dopamine and kinematics of graphomotor functions. Human Movement Sci 25:492–509.

    Google Scholar 

  • Laver J, Moore MAS (1989) Clinical use of recombinant human hematopoietic growth factors. J Natl Cancer Inst 81: 1370–1382.

    CAS  PubMed  Google Scholar 

  • Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH (2004) Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103:1669–1675.

    CAS  PubMed  Google Scholar 

  • Li M, Sendtner M, Smith A (1995) Essential function of LIF receptor in motor neurons. Nature 378:724–727.

    CAS  PubMed  Google Scholar 

  • Lo WC, Hsu CH, Wu AT, Yang LY, Chen WH, Chiu WT, Lai WF, Wu CH, Gelovani JG, Deng WP (2008) A novel cell-based therapy for contusion spinal cord injury using GDNF-delivering NIH3T3 cells with dual reporter genes monitored by molecular imaging. J Nucl Med 49:1512–1519.

    CAS  PubMed  Google Scholar 

  • Maikos JT, Qian Z, Metaxas D, Shreiber DI (2008) Finite element analysis of spinal cord injury in the rat. J Neurotrauma 25:795–816.

    PubMed  Google Scholar 

  • Martinez C, Hofmann TJ, Marino R, Dominici M, Horwitz EM (2007) Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: a novel surface marker for the identification of MSCs. Blood 109:4245–4248.

    CAS  PubMed  Google Scholar 

  • Massague J, Weis-Garcia F (1996) Serine/threonine kinase receptors: mediators of transforming growth factor beta family signals. Cancer Surv 27:41–64.

    CAS  PubMed  Google Scholar 

  • Massague J, Wotton D (2000) Transcriptional control by the TGF-beta/Smad signaling system. EMBO J 19:1745–1754.

    CAS  PubMed  Google Scholar 

  • Massagué J, Andres J, Attisano L, Cheifetz S, López-Casillas F, Ohtsuki M, Wrana JL (1992) TGF-beta receptors. Mol Reprod Dev 32(2):99–104.

    PubMed  Google Scholar 

  • Mazzini L, Mareschi K, Ferrero I, Vassallo E, Oliveri G, Boccaletti R, Testa L, Livigni S, Fagioli F (2006) Autologous mesenchymal stem cells: clinical applications in amyotrophic lateral sclerosis. Neurol Res 28:523–526.

    PubMed  Google Scholar 

  • Mehra A, Wrana JL (2002) TGF-beta and the Smad signal transduction pathway. Biochem Cell Biol 80:605–622.

    CAS  PubMed  Google Scholar 

  • Moore MA (2002) Cytokine and chemokine networks influencing stem cell proliferation, differentiation, and marrow homing. J Cell Biochem 38:29–38.

    Google Scholar 

  • 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 8:202–209.

    CAS  PubMed  Google Scholar 

  • Nomura H, Tator CH, Shoichet MS (2006) Bioengineered strategies for spinal cord repair. J Neurotrauma 23:496–507.

    PubMed  Google Scholar 

  • Olanow CW, Obeso JA, Stocchi F (2006) Drug insight: continuous dopaminergic stimulation in the treatment of Parkinson’s disease. Nat Clin Pract Neurol 2:382–392.

    CAS  PubMed  Google Scholar 

  • Ong SY, Dai H, Leong KW (2006) Hepatic differentiation potential of commercially available human mesenchymal stem cells. Tissue Eng 12:3477–3485.

    CAS  PubMed  Google Scholar 

  • Osawa H, Yamabe H, Kaizuka M, Tamura N, Tsunoda S, Shirato KI, Okumura K (1997) Systemic lupus erythematosus associated with transverse myelitis and parkinsonian symptoms. Lupus 6:613–615.

    CAS  PubMed  Google Scholar 

  • Padovan CS, Jahn K, Birnbaum T, Reich P, Sostak P, Strupp M, Straube A (2003) Expression of neuronal markers in differentiated marrow stromal cells and CD133+ stem-like cells. Cell Transplant 12:839–848.

    PubMed  Google Scholar 

  • Pan W, Cain C, Yu Y, Kastin AJ (2006) Receptor-mediated transport of LIF across blood-spinal cord barrier is upregulated after spinal cord injury. J Neuroimmunol 174:119–125.

    CAS  PubMed  Google Scholar 

  • Perrier AL, Studer L (2003) Making and repairing the mammalian brain–in vitro production of dopaminergic neurons. Semin Cell Dev Biol 14:181–189.

    CAS  PubMed  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147.

    CAS  PubMed  Google Scholar 

  • Planchamp V, Bermel C, Tönges L, Ostendorf T, Kügler S, Reed JC, Kermer P, Bähr M, Lingor P (2008) BAG1 promotes axonal outgrowth and regeneration in vivo via Raf-1 and reduction of ROCK activity. Brain 131:2606–2619.

    PubMed  Google Scholar 

  • Potian JA, Aviv H, Ponzio NM, Harrison JS, Rameshwar P (2003) Veto-like activity of mesenchymal stem cells: Functional discrimination between cellular responses to alloantigens and recall antigens. J Immunol 171: 3426–3434.

    CAS  PubMed  Google Scholar 

  • Ramasamy R, Tong CK, Seow HF, Vidyadaran S, Dazzi F (2008) The immunosuppressive effects of human bone marrow-derived mesenchymal stem cells target T cell proliferation but not its effector function. Cell Immunol 251: 131–136.

    CAS  PubMed  Google Scholar 

  • Reis HJ, Rosa DV, Guimarães MM, Souza BR, Barros AG, Pimenta FJ, Souza RP, Torres KC, Romano-Silva MA (2007) Is DARPP-32 a potential therapeutic target? Expert Opin Ther Targets 11:1649–1661.

    CAS  PubMed  Google Scholar 

  • Roberts AB, Sporn MB (1993) Physiological actions and clinical applications of transforming growth factor-beta (TGF-beta). Growth Factors 8:1–19.

    CAS  PubMed  Google Scholar 

  • Roh JK, Jung KH, Chu K (2008) Adult stem cell transplantation in stroke: its limitations and prospects. Curr Stem Cell Res Ther 3:185–196.

    CAS  PubMed  Google Scholar 

  • Sanberg PR (2007) Neural stem cells for Parkinson’s disease: to protect and repair. Proc Natl Acad Sci U S A 104:11869–11870.

    CAS  PubMed  Google Scholar 

  • Sasaki M, Abe R, Fujita Y, Ando S, Inokuma D, Shimizu H (2008) Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. J Immunol 180:2581–2587.

    CAS  PubMed  Google Scholar 

  • Sato M, Muragaki Y, Saika S, Roberts AB, Ooshima A (2003) Targeted disruption of TGF-beta1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J Clin Invest 112:1486–1494.

    CAS  PubMed  Google Scholar 

  • Schmidt CE, Leach JB (2003) Neural tissue engineering: strategies for repair and regeneration. Annu Rev Biomed Eng 5:293–347.

    CAS  PubMed  Google Scholar 

  • Sekhon LH, Fehlings MG (2001) Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine 26:S2–S12.

    CAS  PubMed  Google Scholar 

  • Shi Y, Massagué J (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113:685–700.

    CAS  PubMed  Google Scholar 

  • Shigetomi S, Fukuchi S (1994) Recent aspect of the role of peripheral dopamine and its receptors in the pathogenesis of hypertension. Fukushima J Med Sci 40:69–83.

    CAS  PubMed  Google Scholar 

  • Smith DH, Wolf JA, Meaney DF (2001) A new strategy to produce sustained growth of central nervous system axons: continuous mechanical tension. Tissue Eng 7:131–139.

    CAS  PubMed  Google Scholar 

  • Sokol JP, Schiemann WP (2004) Cystatin C antagonizes transforming growth factor beta signaling in normal and cancer cells. Mol Cancer Res 2:183–195.

    CAS  PubMed  Google Scholar 

  • Stagg J, Pommey S, Eliopoulos N, Galipeau J (2006) Interferon-gama-stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell. Blood 107:2570–2577.

    CAS  PubMed  Google Scholar 

  • Staples M, Daniel K, Cima MJ, Langer R (2006) Application of micro- and nano-electromechanical devices to drug delivery. Pharm Res 23:847–863.

    CAS  PubMed  Google Scholar 

  • Tansey MG, McCoy MK, Frank-Cannon TC (2007) Neuroinflammatory mechanisms in Parkinson’s disease: Potential environmental triggers, pathways, and targets for early therapeutic intervention. Expl Neurol 208:1–25.

    CAS  Google Scholar 

  • Tebar LA, Géranton SM, Parsons-Perez C, Fisher AS, Bayne R, Smith AJ, Turmaine M, Perez-Luz S, Sheasby A, De Felipe C, Ruff C, Raivich G, Hunt SP (2008) Deletion of the mouse RegIIIbeta (Reg2) gene disrupts ciliary neurotrophic factor signaling and delays myelination of mouse cranial motor neurons. Proc Natl Acad Sci U S A 105: 11400–11405.

    CAS  PubMed  Google Scholar 

  • Thompson BC, Moulton SE, Ding J, Richardson R, Cameron A, O‘Leary S, Wallace GG, Clark GM (2006) Optimising the incorporation and release of a neurotrophic factor using conducting polypyrrole. J Control Release 116:285–294.

    CAS  PubMed  Google Scholar 

  • Thompson C, Powrie F (2004) Regulatory T cells. Curr Opin Pharmacol 4:408–414.

    CAS  PubMed  Google Scholar 

  • Thompson JA, Zembrzycki A, Mansouri A, Ziman M (2008) Pax7 is requisite for maintenance of a subpopulation of superior collicular neurons and shows a diverging expression pattern to Pax3 during superior collicular development. BMC Dev Biol 8:62.

    PubMed  Google Scholar 

  • Tonge D, Chan K, Zhu N, Panjwani A, Arno M, Lynham S, Ward M, Snape A, Pizzey J (2008) Enhancement of axonal regeneration by in vitro conditioning and its inhibition by cyclopentenone prostaglandins. J Cell Sci 121:2565–2577.

    CAS  PubMed  Google Scholar 

  • Trzaska KA, Kuzhikandathil EV, Rameshwar P (2007) Specification of a dopaminergic phenotype from adult human mesenchymal stem cells. Stem Cells 25:2797–2808.

    CAS  PubMed  Google Scholar 

  • Trzaska KA, Rameshwar P (2007) Current advances in the treatment of Parkinson’s disease with stem cells. Curr Neurovas Res 4:99–109.

    CAS  Google Scholar 

  • Wadhwa R, Lagenaur CF, Cui XT (2006) Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode. J Control Release 110: 531–541.

    CAS  PubMed  Google Scholar 

  • Willerth SM, Sakiyama-Elbert SE (2007) Approaches to neural tissue engineering using scaffolds for drug delivery. Adv Drug Dev Rev 59:325–338.

    CAS  Google Scholar 

  • Wrana JL (2000) Regulation of Smad activity. Cell 100: 189–192.

    CAS  PubMed  Google Scholar 

  • Xie J, Willerth SM, Li X, Macewan MR, Rader A, Sakiyama-Elbert SE, Younan X (2008) The differentiation of embryonic stem cells seeded on electrospun nanofibers into neural lineages. Biomaterials 30:354–362.

    PubMed  Google Scholar 

  • Yamashita T, Deguchi K, Sehara Y, Lukic-Panin V, Zhang H, Kamiya T, Abe K (2008) Therapeutic strategy for ischemic stroke. Neurochem Res 34:707–710.

    PubMed  Google Scholar 

  • Yamashita T, Deguchi K, Sehara Y, Lukic-Panin V, Zhang H, Kamiya T, Abe K, Yamauchi K, Osuka K, Takayasu M, Usuda N, Nakazawa A, Nakahara N, Yoshida M, Aoshima C, Hara M, Yoshida J (2006) Activation of JAK/STAT signaling in neurons following spinal cord injury in mice. J Neurochem 96:1060–1070.

    Google Scholar 

  • Yoo SW, Kim SS, Lee SY, Lee HS, Kim HS, Lee YD, Suh-Kim H (2008) Mesenchymal stem cells promote proliferation of endogenous neural stem cells and survival of newborn cells in a rat stroke model. Exp Mol Med 40:387–397.

    CAS  PubMed  Google Scholar 

  • Young W (2000) Molecular and cellular mechanisms of spinal cord injury therapies. In: Neurobiology of Spinal Cord Injury (Kalb RG, Strittmatter SM, eds.), p. 241. Humana Press, Totowa.

    Google Scholar 

  • Yune TY, Chang MJ, Kim SJ, Lee YB, Shin SW, Rhim H, Kim YC, Shin ML, Oh YJ, Han CT, Markelonis GJ, Oh TH (2003) Increased production of tumor necrosis factor-alpha induces apoptosis after traumatic spinal cord injury in rats. J Neurotrauma 20:207–219.

    PubMed  Google Scholar 

  • Zai LJ, Yoo S, Wrathall JR (2005) Increased growth factor expression and cell proliferation after contusive spinal cord injury. Brain Res 1052:147–155.

    CAS  PubMed  Google Scholar 

  • Zhang X, Zeng Y, Zhang W, Wang J, Wu J, Li J (2007) Co-transplantation of neural stem cells and NT-3-overexpressing Schwann cells in transected spinal cord. J Neurotrauma 24:1863–1877.

    PubMed  Google Scholar 

Download references

Acknowledgement

This work was supported by the FM Kirby Foundation.

Author information

Authors and Affiliations

  1. Department of Medicine, UMDNJ-New Jersey Medical School, Newark, NJ, USA

    Cecile King, Shyam Patel & Pranela Rameshwar

  2. Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, USA

    Treena Livingston Arinzeh

Authors
  1. Cecile King
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shyam Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Treena Livingston Arinzeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pranela Rameshwar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pranela Rameshwar .

Editor information

Editors and Affiliations

  1. Inst. Química, Universidade de São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, 05508-900, Brazil

    Henning Ulrich

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

King, C., Patel, S., Arinzeh, T.L., Rameshwar, P. (2010). Dual Roles of Mesenchymal Stem Cells in Spinal Cord Injury: Cell Replacement Therapy and as a Model System to Understand Axonal Repair. In: Ulrich, H. (eds) Perspectives of Stem Cells. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3375-8_17

Download citation

Publish with us

Policies and ethics

Search

Navigation