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Autologous stem cells in neurology: is there a future?

  • Basic Neurosciences, Genetics and Immunology - Review article
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Abstract

Stem cells seem very promising in the treatment of degenerative neurological diseases for which there are currently no or limited therapeutic strategies. However, their clinical application meets many regulatory hurdles. This article gives an overview of stem cells, their potential healing capacities as well as their identified and potential risks, such as tumor formation, unwanted immune responses and the transmission of adventitious agents. As there is no clinical experience with embryonic and induced pluripotent stem cells (as the result of their unacceptable risk on tumor formation), most attention will be paid to fresh autologous adult stem cells (ASCs). To evaluate eventual clinical benefits, preclinical studies are essential, though their value is limited as in these studies, various types of stem cells, with different histories of procurement and culturing, are applied in various concentrations by various routes of administration. On top of that, in most animal studies allogenic human, thus non-autologous, stem cells are applied, which might mask the real effects. More reliable, though small-sized, clinical trials with autologous ASCs did show satisfying clinical benefits in regenerative medicine, without major health concerns. One should wonder, though, why it is so hard to get compelling evidence for the healing and renewing capacities of these stem cells when these cells indeed are really essential for tissue repair during life. Why so many hurdles have to be taken before health authorities such as the European Medicine Agency (EMA) and/or the Food and Drug Administration (FDA) approve stem cells in the treatment of (especially no-option) patients.

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References

  • Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815–1822

    Article  PubMed  CAS  Google Scholar 

  • Andersson AK (2011) Embryonic stem cells and property rights. J med philos 36:221–242

    Article  PubMed  Google Scholar 

  • Andres RH, Choi R, Steinberg GK, Guzman R (2008) Potential of adult neural stem cells in stroke therapy. Regen med 3:893–905

    Article  PubMed  Google Scholar 

  • Assmus B, Rolf A, Erbs S et al (2010) Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction. Circ Heart Fail 3:89–96

    Article  PubMed  Google Scholar 

  • Astori G, Soncin S, Lo Cicero V, Siclari F, Surder D, Turchetto L, Soldati G, Moccetti T (2010) Bone marrow derived stem cells in regenerative medicine as advanced therapy medicinal products. Am J Transl Res 2:285–295

    PubMed  Google Scholar 

  • Asumda FZ, Chase PB (2011) Age-related changes in rat bone-marrow mesenchymal stem cell plasticity. BMC Cell Biol 12:44

    Article  PubMed  CAS  Google Scholar 

  • Bakshi A, Barshinger AL, Swanger SA, Madhavani V, Shumsky JS, Neuhuber B, Fischer I (2006) Lumbar puncture delivery of bone marrow stromal cells in spinal cord contusion: a novel method for minimally invasive cell transplantation. J Neurotrauma 23:55–65

    Article  PubMed  Google Scholar 

  • Barzilay R, Levy YS, Melamed E, Offen D (2006) Adult stem cells for neuronal repair. Isr Med Assoc J IMAJ 8:61–66

    Google Scholar 

  • Bouchez G, Sensebe L, Vourc’h P et al (2008) Partial recovery of dopaminergic pathway after graft of adult mesenchymal stem cells in a rat model of Parkinson’s disease. Neurochem Int 52:1332–1342

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  • Cho GW, Noh MY, Kim HY, Koh SH, Kim KS, Kim SH (2010) Bone marrow-derived stromal cells from amyotrophic lateral sclerosis patients have diminished stem cell capacity. Stem Cells Dev 19:1035–1042

    Article  PubMed  CAS  Google Scholar 

  • Courtine G, Bunge MB, Fawcett JW et al (2007) Can experiments in nonhuman primates expedite the translation of treatments for spinal cord injury in humans? Nat Med 13:561–566

    Article  PubMed  CAS  Google Scholar 

  • Crigler L, Robey RC, Asawachaicharn A, Gaupp D, Phinney DG (2006) Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol 198:54–64

    Article  PubMed  CAS  Google Scholar 

  • Dezawa M, Kanno H, Hoshino M et al (2004) Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Investig 113:1701–1710

    PubMed  CAS  Google Scholar 

  • Dimmeler S, Leri A (2008) Aging and disease as modifiers of efficacy of cell therapy. Circ Res 102:1319–1330

    Article  PubMed  CAS  Google Scholar 

  • Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 8:315–317

    Article  PubMed  CAS  Google Scholar 

  • Forostyak S, Jendelova P, Kapcalova M, Arboleda D, Sykova E (2011) Mesenchymal stromal cells prolong the lifespan in a rat model of amyotrophic lateral sclerosis. Cytotherapy 13:1036–1046

    Article  PubMed  CAS  Google Scholar 

  • Gerdoni E, Gallo B, Casazza S et al (2007) Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis. Ann neurol 61:219–227

    Article  PubMed  CAS  Google Scholar 

  • Gnecchi M, Zhang Z, Ni A, Dzau VJ (2008) Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res 103:1204–1219

    Article  PubMed  CAS  Google Scholar 

  • Hemmat S, Lieberman DM, Most SP (2010) An introduction to stem cell biology. Facial plast surg FPS 26:343–349

    Article  CAS  Google Scholar 

  • Holowiecki J (2008) Indications for hematopoietic stem cell transplantation. Pol Arch Med Wewn 118:658–663

    PubMed  Google Scholar 

  • Huang X, Kim JM, Kong TH (2009) GM-CSF inhibits glial scar formation and shows long-term protective effect after spinal cord injury. J Neurol Sci 277:87–97

    Article  PubMed  CAS  Google Scholar 

  • Jackson JS, Golding JP, Chapon C, Jones WA, Bhakoo KK (2010) Homing of stem cells to sites of inflammatory brain injury after intracerebral and intravenous administration: a longitudinal imaging study. Stem Cell Res Ther 1:17

    Article  PubMed  Google Scholar 

  • Jung D, Ha IJ, Kang BT, Kim JW, Quan FS, Lee JH, Woo EJ, Park HM (2009) A comparison of autologous and allogenic bone marrow-derived mesenchymal stem cell transplantation in canine spinal cord injury. J Neurol Sci 285:67–77

    Article  PubMed  Google Scholar 

  • Junker JP, Sommar P, Skog M, Johnson H, Kratz G (2010) Adipogenic, chondrogenic and osteogenic differentiation of clonally derived human dermal fibroblasts. Cells Tissues Organs 191:105–118

    Article  PubMed  Google Scholar 

  • Kamei N, Tanaka N, Oishi Y, Hamasaki T, Nakanishi K, Sakai N, Ochi M (2007) BDNF, NT-3, and NGF released from transplanted neural progenitor cells promote corticospinal axon growth in organotypic cocultures. Spine 32:1272–1278

    Article  PubMed  Google Scholar 

  • Kassis I, Grigoriadis N, Gowda-Kurkalli B, Mizrachi-Kol R, Ben-Hur T, Slavin S, Abramsky O, Karussis D (2008) Neuroprotection and immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis. Arch Neurol 65:753–761

    Article  PubMed  Google Scholar 

  • Keeney M, Chin-Yee I, Weir K, Popma J, Nayar R, Sutherland DR (1998) Single platform flow cytometric absolute CD34 + cell counts based on the ISHAGE guidelines. International Society of Hematotherapy and Graft Engineering. Cytometry 34:61–70

    Article  PubMed  CAS  Google Scholar 

  • Koshizuka S, Okada S, Okawa A et al (2004) 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 63:64–72

    PubMed  Google Scholar 

  • 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 Off J Middle East Soc Organ Transplant 7:241–248

    Google Scholar 

  • Lee AS, Tang C, Cao F et al (2009) Effects of cell number on teratoma formation by human embryonic stem cells. Cell Cycle 8:2608–2612

    Article  PubMed  CAS  Google Scholar 

  • Levy YS, Bahat-Stroomza M, Barzilay R et al (2008) Regenerative effect of neural-induced human mesenchymal stromal cells in rat models of Parkinson’s disease. Cytotherapy 10:340–352

    Article  PubMed  CAS  Google Scholar 

  • Li J, Zhu H, Liu Y et al (2010a) Human mesenchymal stem cell transplantation protects against cerebral ischemic injury and upregulates interleukin-10 expression in Macaca fascicularis. Brain Res 1334:65–72

    Article  PubMed  CAS  Google Scholar 

  • Li TS, Kubo M, Ueda K, Murakami M, Mikamo A, Hamano K (2010b) Impaired angiogenic potency of bone marrow cells from patients with advanced age, anemia, and renal failure. J Thorac Cardiovasc Surg 139:459–465

    Article  PubMed  Google Scholar 

  • Mayshar Y, Ben-David U, Lavon N et al (2010) Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. Cell Stem Cell 7:521–531

    Article  PubMed  CAS  Google Scholar 

  • Neuhuber B, Himes BT, Shumsky JS, Gallo G, Fischer I (2005) Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations. Brain Res 1035:73–85

    Article  PubMed  CAS  Google Scholar 

  • Pittenger MF, Martin BJ (2004) Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 95:9–20

    Article  PubMed  CAS  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

  • Riordan NH, Chan K, Marleau AM, Ichim TE (2007) Cord blood in regenerative medicine: do we need immune suppression? J Transl Med 5:8

    Article  PubMed  Google Scholar 

  • Samdani AF, Paul C, Betz RR, Fischer I, Neuhuber B (2009) Transplantation of human marrow stromal cells and mono-nuclear bone marrow cells into the injured spinal cord: a comparative study. Spine 34:2605–2612

    Article  PubMed  Google Scholar 

  • Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, Muroi K, Ozawa K (2007) Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 109:228–234

    Article  PubMed  CAS  Google Scholar 

  • Scerpa MC, Daniele N, Landi F et al (2011) Automated washing of human progenitor cells: evaluation of apoptosis and cell necrosis. Transfus Med 21:402–407

    Article  PubMed  CAS  Google Scholar 

  • Schofield R (1983) The stem cell system. Biomed Pharmacother 37:375–380

    PubMed  CAS  Google Scholar 

  • Sekhon LH, Fehlings MG (2001) Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine (Phila Pa 1976) 26:S2–S12

    Article  CAS  Google Scholar 

  • Shi E, Kazui T, Jiang X, Washiyama N, Yamashita K, Terada H, Bashar AH (2007) Therapeutic benefit of intrathecal injection of marrow stromal cells on ischemia-injured spinal cord. Ann Thorac Surg 83:1484–1490

    Article  PubMed  Google Scholar 

  • Siddiq S, Pamphilon D, Brunskill S, Doree C, Hyde C, Stanworth A (2009) Bone marrow harvest versus peripheral stem cell collection for haemopoietic stem cell donation in healthy donors. Cochrane Database Syst Rev, 21(1):CD006406

    Google Scholar 

  • Stadtfeld M, Hochedlinger K (2010) Induced pluripotency: history, mechanisms, and applications. Genes Dev 24:2239–2263

    Article  PubMed  CAS  Google Scholar 

  • Stamatovic SM, Keep RF, Andjelkovic AV (2008) Brain endothelial cell–cell junctions: how to “open” the blood brain barrier. Curr Neuropharmacol 6:179–192

    Article  PubMed  CAS  Google Scholar 

  • Stenderup K, Justesen J, Clausen C, Kassem M (2003) Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33:919–926

    Article  PubMed  Google Scholar 

  • Taguchi A, Soma T, Tanaka H (2004) Administration of CD34 + cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest 114:330–338

    PubMed  CAS  Google Scholar 

  • Van Tongeren RB, Hamming JF, Fibbe WE, Van Weel V, Frerichs SJ, Stiggelbout AM, Van Bockel JH, Lindeman JH (2008) Intramuscular or combined intramuscular/intra-arterial administration of bone marrow mononuclear cells: a clinical trial in patients with advanced limb ischemia. J Cardiovasc Surg (Torino) 49:51–58

    Google Scholar 

  • Veeraputhiran M, Theus JW, Pesek G, Barlogie B, Cottler-Fox M (2010) Viability and engraftment of hematopoietic progenitor cells after long-term cryopreservation: effect of diagnosis and percentage dimethyl sulfoxide concentration. Cytotherapy 12:764–766

    Article  PubMed  CAS  Google Scholar 

  • Wragg A, Mellad JA, Beltran LE et al (2008) VEGFR1/CXCR4-positive progenitor cells modulate local inflammation and augment tissue perfusion by a SDF-1-dependent mechanism. J Mol Med 86:1221–1232

    Article  PubMed  CAS  Google Scholar 

  • Wright KT, El Masri W, Osman A, Chowdhury J, Johnson WE (2010) Bone marrow for the treatment of spinal cord injury: mechanisms and clinical application. Stem Cells 29(2):169–178

    Article  Google Scholar 

  • Wyndaele M, Wyndaele JJ (2006) Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal Cord 44:523–529

    Article  PubMed  CAS  Google Scholar 

  • Xu H, Miki K, Ishibashi S et al (2010) Transplantation of neuronal cells induced from human mesenchymal stem cells improves neurological functions after stroke without cell fusion. J Neurosci Res 88:3598–3609

    Article  PubMed  CAS  Google Scholar 

  • Yang B, Strong R, Sharma S et al (2011) Therapeutic time window and dose response of autologous bone marrow mononuclear cells for ischemic stroke. J Neurosci Res 89:833–839

    Article  PubMed  CAS  Google Scholar 

  • Ye Y, Zeng YM, Wan MR, Lu XF (2011) Induction of human bone marrow mesenchymal stem cells differentiation into neural-like cells using cerebrospinal fluid. Cell Biochem Biophys 59:179–184

    Article  PubMed  CAS  Google Scholar 

  • Zappia E, Casazza S, Pedemonte E et al (2005) Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood 106:1755–1761

    Article  PubMed  CAS  Google Scholar 

  • Zeng R, Wang LW, Hu ZB et al (2011) Differentiation of human bone marrow mesenchymal stem cells into neuron-like cells in vitro. Spine (Phila Pa 1976) 36(13):997–1005

    Article  Google Scholar 

  • Zhang J, Li Y, Chen J et al (2005) Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice. Exp Neurol 195:16–26

    Article  PubMed  CAS  Google Scholar 

  • Zhang C, Zhou C, Teng JJ, Zhao RL, Song YQ (2009) Multiple administrations of human marrow stromal cells through cerebrospinal fluid prolong survival in a transgenic mouse model of amyotrophic lateral sclerosis. Cytotherapy 11:299–306

    Article  PubMed  CAS  Google Scholar 

  • Zietlow R, Lane EL, Dunnett SB, Rosser AE (2008) Human stem cells for CNS repair. Cell Tissue Res 331:301–322

    Article  PubMed  Google Scholar 

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Correspondence to Johannes P. J. M. de Munter.

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de Munter, J.P.J.M., Wolters, E.C. Autologous stem cells in neurology: is there a future?. J Neural Transm 120, 65–73 (2013). https://doi.org/10.1007/s00702-012-0913-9

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  • DOI: https://doi.org/10.1007/s00702-012-0913-9

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