Abstract
In this review article, we primarily focus on data generated in our laboratory using bone marrow stromal cells (BMSCs) for the treatment of stroke, and other central nervous system (CNS) disorders, such as traumatic brain injury, intracerebral hemorrhage, spinal cord injury, Parkinson’s disease, multiple sclerosis and brain tumor in rodents. BMSCs obtained from donor rats, mice or humans have been transplanted into the CNS via local and systemic routes. BMSCs selectively target damaged tissue, promote neurological functional recovery, and remodel brain architecture. Although some BMSCs express proteins phenotypic of neural cells, it is highly unlikely that benefit is derived by replacement of damaged tissues and rewiring brain with transdifferentiated BMSCs. The far more reasonable explanation is that BMSCs secrete and induce within parenchymal cells expression of growth or trophic factors that activate endogenous restorative processes, e.g., angiogenesis, synaptogenesis, gliogenesis and neurogenesis (Figure 4.1).
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Keywords
- Traumatic Brain Injury
- Experimental Autoimmune Encephalomyelitis
- Bone Marrow Stromal Cell
- Focal Cerebral Ischemia
- Central Nervous System Disease
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4.6. References
S. C. Cramer and M. Chopp, Recovery recapitulates ontogeny, Trends Neurosci 23(6), 265–271 (2000).
N. Duggal, R. Schmidt-Kastner and A. M. Hakim, Nestin expression in reactive astrocytes following focal cerebral ischemia in rats, Brain Res 768, 1–9 (1997).
Y. Li and M. Chopp, Temporal profile of nestin expression after focal cerebral ischemia in adult rat, Brain Res 838, 1–10 (1999).
R. P. Stroemer, T. A. Kent and C. E. Hulsebosch, Neocortical neural sprouting, synaptogenesis, and behavioral recovery after neocortical infarction in rats, Stroke 26(11), 2135–2144 (1995).
Y. Li, N. Jiang, C. Powers and M. Chopp, Neuronal damage and plasticity identified by microtubule-associated protein 2, growth-associated protein 43, and cyclin d1 immunoreactivity after focal cerebral ischemia in rats, Stroke 29(9), 1972–1980 (1998).
Z. Zhang and M. Chopp, Vascular endothelial growth factor and angiopoietins in focal cerebral ischemia, Trends Cardiovasc Med 12(2), 62–66 (2002).
J. Chen, Y. Li, M. Katakowski, X. Chen, L. Wang, D. Lu, M. Lu, S. C. Gautam and M. Chopp, Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat, J Neurosci Res 73(6), 778–786 (2003).
R. Zhang, Z. Zhang, L. Wang, Y. Wang, A. Gousev, L. Zhang, K. L. Ho, C. Morshead and M. Chopp, Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats, J Cereb Blood Flow Metab 24(4), 441–448 (2004).
G. Kempermann, H. van Praag and F. H. Gage, Activity-dependent regulation of neuronal plasticity and self repair, Prog Brain Res 127, 35–48 (2000).
S. E. Haynesworth, M. A. Baber and A. I. Caplan, Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro: Effects of dexamethasone and il-1 alpha, J Cell Physiol 166(3), 585–592 (1996).
S. P. Dormady, O. Bashayan, R. Dougherty, X. M. Zhang and R. S. Basch, Immortalized multipotential mesenchymal cells and the hematopoietic microenvironment, J Hematother Stem Cell Res 10(1), 125–140 (2001).
J. Rohwedel, K. Guan, W. Zuschratter, S. Jin, G. Ahnert-Hilger, D. Furst, R. Fassler and A. M. Wobus, Loss of beta1 integrin function results in a retardation of myogenic, but an acceleration of neuronal, differentiation of embryonic stem cells in vitro, Dev Biol 201(2), 167–184 (1998).
J. Chen, Y. Li, L. Wang, Z. Zhang, D. Lu, M. Lu and M. Chopp, Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats, Stroke 32(4), 1005–1011 (2001).
J. Chen, Y. Li, L. Wang, M. Lu, X. Zhang and M. Chopp, Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats, J Neurol Sci 189, 49–57 (2001).
Y. Li, J. Chen, L. Wang, M. Lu and M. Chopp, Treatment of stroke in rat with intracarotid administration of marrow stromal cells, Neurology 56(12), 1666–1672 (2001).
Y. Li, J. Chen, X. G. Chen, L. Wang, S. C. Gautam, Y. X. Xu, M. Katakowski, L. J. Zhang, M. Lu, N. Janakiraman and M. Chopp, Human marrow stromal cell therapy for stroke in rat: Neurotrophins and functional recovery, Neurology 59(4), 514–523 (2002).
J. Chen, Y. Li, R. Zhang, M. Katakowski, S. C. Gautam, Y. Xu, M. Lu, Z. Zhang and M. Chopp, Combination therapy of stroke in rats with a nitric oxide donor and human bone marrow stromal cells enhances angiogenesis and neurogenesis, Brain Res 1005, 21–28 (2004).
Y. Li, J. Chen, C. L. Zhang, L. Wang, D. Lu, M. Katakowski, Q. Gao, L. H. Shen, J. Zhang, M. Lu and M. Chopp, Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells, Glia 49(3), 407–417 (2005).
Y. Li, J. Chen and M. Chopp, Adult bone marrow transplantation after stroke in adult rats, Cell Transplant 10(1), 31–40 (2001).
Y. Li, M. Chopp, J. Chen, L. Wang, S. C. Gautam, Y. X. Xu and Z. Zhang, Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice, J Cereb Blood Flow Metab 20(9), 1311–1319 (2000).
D. Lu, A. Mahmood, L. Wang, Y. Li, M. Lu and M. Chopp, Adult bone marrow stromal cells administered intravenously to rats after traumatic brain injury migrate into brain and improve neurological outcome, Neuroreport 12(3), 559–563 (2001).
D. Lu, Y. Li, L. Wang, J. Chen, A. Mahmood and M. Chopp, Intraarterial administration of marrow stromal cells in a rat model of traumatic brain injury, J Neurotrauma 18(8), 813–819 (2001).
A. Mahmood, D. Lu, L. Yi, J. L. Chen and M. Chopp, Intracranial bone marrow transplantation after traumatic brain injury improving functional outcome in adult rats, J Neurosurg 94(4), 589–595 (2001).
A. Mahmood, D. Lu, L. Wang, Y. Li, M. Lu and M. Chopp, Treatment of traumatic brain injury in female rats with intravenous administration of bone marrow stromal cells, Neurosurgery 49(5), 1196–1203 (2001).
A. Mahmood, D. Lu, L. Wang and M. Chopp, Intracerebral transplantation of marrow stromal cells cultured with neurotrophic factors promotes functional recovery in adult rats subjected to traumatic brain injury, J Neurotrauma 19(12), 1609–1617 (2002).
A. Mahmood, D. Lu, M. Lu and M. Chopp, Treatment of traumatic brain injury in adult rats with intravenous administration of human bone marrow stromal cells, Neurosurgery 53(3), 697–702 (2003).
A. Mahmood, D. Lu and M. Chopp, Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury, J Neurotrauma 21(1), 33–39 (2004).
—, Marrow stromal cell transplantation after traumatic brain injury promotes cellular proliferation within the brain, Neurosurgery 55(5), 1185–1193 (2004).
D. Seyfried, J. Ding, Y. Han, Y. Li, J. Chen and M. Chopp, Intravenous administration of human bone marrow stromal cells improves recovery and reduces neural tissue loss after intracerebral hemorrhage in rats, J Neurosurg 104:1–6 (2006).
M. Chopp, X. H. Zhang, Y. Li, L. Wang, J. Chen, D. Lu, M. Lu and M. Rosenblum, Spinal cord injury in rat: Treatment with bone marrow stromal cell transplantation, Neuroreport 11(13), 3001–3005 (2000).
Y. Li, J. Chen, L. Wang, L. Zhang, M. Lu and M. Chopp, Intracerebral transplantation of bone marrow stromal cells in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of parkinson’s disease, Neurosci Lett 316(2), 67–70 (2001).
J. Zhang, Y. Li, J. Chen, Y. Cui, M. Lu, S. B. Elias, J. B. Mitchell, L. Hammill, P. Vanguri and M. Chopp, Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice, Exp Neurol (in press) (2005).
Z. Zhang, Q. Jiang, F. Jiang, G. Ding, R. Zhang, L. Wang, L. Zhang, A. M. Robin, M. Katakowski and M. Chopp, In vivo magnetic resonance imaging tracks adult neural progenitor cell targeting of brain tumor, Neuroimage 23(1), 281–287 (2004).
T. Schallert, M. Upchurch, N. Lobaugh, S. B. Farrar, W. W. Spirduso, P. Gilliam, D. Vaughn and R. E. Wilcox, Tactile extinction: Distinguishing between sensorimotor and motor asymmetries in rats with unilateral nigrostriatal damage, Pharmacol Biochem Behav 16(3), 455–462 (1982).
L. Zhang, T. Schallert, Z. G. Zhang, Q. Jiang, P. Arniego, Q. Li, M. Lu and M. Chopp, A test for detecting long-term sensorimotor dysfunction in the mouse after focal cerebral ischemia, J Neurosci Methods 117(2), 207–214 (2002).
J. Chen, C. Zhang, H. Jiang, Y. Li, L. Zhang, A. Robin, M. Katakowski, M. Lu and M. Chopp, Atorvastatin induction of vegf and bdnf promotes brain plasticity after stroke in mice, J Cereb Blood Flow Metab 25(2), 281–290 (2005).
D. Lu, A. Mahmood, A. Goussev, T. Schallert, C. Qu, Z. G. Zhang, Y. Li, M. Lu and M. Chopp, Atorvastatin reduction of intravascular thrombosis, increase in cerebral microvascular patency and integrity, and enhancement of spatial learning in rats subjected to traumatic brain injury, J Neurosurg 101(5), 813–821 (2004).
M. Lu, J. Chen, D. Lu, L. Yi, A. Mahmood and M. Chopp, Global test statistics for treatment effect of stroke and traumatic brain injury in rats with administration of bone marrow stromal cells, J Neurosci Methods 128, 183–190 (2003).
R. L. Zhang, M. Chopp, Z. G. Zhang, Q. Jiang and J. R. Ewing, A rat model of focal embolic cerebral ischemia, Brain Res 766, 83–92 (1997).
Z. Zhang, M. Chopp, R. L. Zhang and A. Goussev, A mouse model of embolic focal cerebral ischemia, J Cereb Blood Flow Metab 17(10), 1081–1088 (1997).
J. H. Garcia, Y. Yoshida, H. Chen, Y. Li, Z. G. Zhang, J. Lian, S. Chen and M. Chopp, Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat, Am J Pathol 142(2), 623–635 (1993).
Y. Li, V. G. Sharov, N. Jiang, C. Zaloga, H. N. Sabbah and M. Chopp, Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat, Am J Pathol 146(5), 1045–1051 (1995).
Y. Li, M. Chopp, N. Jiang, F. Yao and C. Zaloga, Temporal profile of in situ DNA fragmentation after transient middle cerebral artery occlusion in the rat, J Cereb Blood Flow Metab 15(3), 389–397 (1995).
Y. Li, M. Chopp, J. H. Garcia, Y. Yoshida, Z. G. Zhang and S. R. Levine, Distribution of the 72-kd heat-shock protein as a function of transient focal cerebral ischemia in rats, Stroke 23(9), 1292–1298 (1992).
Y. Li, M. Chopp, Z. G. Zhang, C. Zaloga, L. Niewenhuis and S. Gautam, P53-immunoreactive protein and p53 mrna expression after transient middle cerebral artery occlusion in rats, Stroke 25(4), 849–855 (1994).
Y. Li, M. Chopp, C. Powers and N. Jiang, Immunoreactivity of cyclin d1/cdk4 in neurons and oligodendrocytes after focal cerebral ischemia in rat, J Cereb Blood Flow Metab 17(8), 846–856 (1997).
R. L. Zhang, M. Chopp, Y. Li, C. Zaloga, N. Jiang, M. L. Jones, M. Miyasaka and P. A. Ward, Antiicam-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat, Neurology 44(9), 1747–1751 (1994).
Z. G. Zhang, M. Chopp, F. Bailey and T. Malinski, Nitric oxide changes in the rat brain after transient middle cerebral artery occlusion, J Neurol Sci 128(1), 22–27 (1995).
Z. G. Zhang, L. Zhang, Q. Jiang and M. Chopp, Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse, Circ Res 90(3), 284–288 (2002).
D. Lu, P. R. Sanberg, A. Mahmood, Y. Li, L. Wang, J. Sanchez-Ramos and M. Chopp, Intravenous administration of human umbilical cord blood reduces neurological deficit in the rat after traumatic brain injury, Cell Transplant 11(3), 275–281 (2002).
K. R. McIntosh, K. Beggs, R. Dodds, A. Lyubimov, A. Bartholomew, C. Cobbs, A. Smith and A. Moseley, High dose administration of allogeneic mesenchymal stem cells to immunocompetent baboons. Supplement of the Bone Marrow Transplantation 29, S38. (Abstract) (2002).
W. T. Tse, J. D. Pendleton, W. M. Beyer, M. C. Egalka and E. C. Guinan, Suppression of allogeneic t-cell proliferation by human marrow stromal cells: Implications in transplantation, Transplantation 75(3), 389–397 (2003).
O. N. Koc, S. L. Gerson, B. W. Cooper, S. M. Dyhouse, S. E. Haynesworth, A. I. Caplan and H. M. Lazarus, Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and cultureexpanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy, J Clin Oncol 18(2), 307–316 (2000).
O. N. Koc and H. M. Lazarus, Mesenchymal stem cells: Heading into the clinic, Bone Marrow Transplant 27(3), 235–239 (2001).
P. Mandalfino, G. Rice, A. Smith, J. L. Klein, L. Rystedt and G. C. Ebers, Bone marrow transplantation in multiple sclerosis, J Neurol 247(9), 691–695 (2000).
O. Y. Bang, J. S. Lee, P. H. Lee and G. Lee, Autologous mesenchymal stem cell transplantation in stroke patients, Ann Neurol 57(6), 874–882 (2005).
L. Wang, Y. Li, J. Chen, S. C. Gautam, Z. Zhang, M. Lu and M. Chopp, Ischemic cerebral tissue and mcp-1 enhance rat bone marrow stromal cell migration in interface culture, Exp Hematol 30(7), 831–836 (2002).
L. Wang, Y. Li, X. Chen, J. Chen, S. C. Gautam, Y. Xu and M. Chopp, Mcp-1, mip-1, il-8 and ischemic cerebral tissue enhance human bone marrow stromal cell migration in interface culture, Hematology 7(2), 113–117 (2002).
J. Zhang, Y. Li, J. Chen, M. Yang, M. Katakowski, M. Lu and M. Chopp, Expression of insulin-like growth factor 1 and receptor in ischemic rats treated with human marrow stromal cells, Brain Res 1030(1), 19–27 (2004).
X. Chen, Y. Li, L. Wang, M. Katakowski, L. Zhang, J. Chen, Y. Xu, S. C. Gautam and M. Chopp, Ischemic rat brain extracts induce human marrow stromal cell growth factor production, Neuropathology 22(4), 275–279 (2002).
X. Chen, M. Katakowski, Y. Li, D. Lu, L. Wang, L. Zhang, J. Chen, Y. Xu, S. Gautam, A. Mahmood and M. Chopp, Human bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts: Growth factor production, J Neurosci Res 69(5), 687–691 (2002).
X. G. Chen, Li Y, Wang L, Katakowski M, Zhang L.J, Chen J, Xu Y.X, Gautam S.C, Chopp M, Calcium promotes secretion of growth factors from human bone marrow stromal cells (hMSCs) and tube formation of human brain microvessel endothelial cells, Stroke 33(1), 401 (Abstract) (2002).
C. Guegan, B. Onteniente, Y. Makiura, M. Merad-Boudia, I. Ceballos-Picot and B. Sola, Reduction of cortical infarction and impairment of apoptosis in ngf-transgenic mice subjected to permanent focal ischemia, Brain Res Mol Brain Res 55(1), 133–140 (1998).
Q. Gao, Y. Li and M. Chopp, Bone marrow stromal cells increase astrocyte survival via upregulation of pi3k/akt and mek/erk pathways and stimulate astrocyte trophic factor gene expression after anaerobic insult., Neuroscience, (in press) (2005).
J. Chen, Z. G. Zhang, Y. Li, L. Wang, Y. X. Xu, S. C. Gautam, M. Lu, Z. Zhu and M. Chopp, Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats, Circ Res 92(6), 692–699 (2003).
Y. Tamada, C. Fukiage, D. L. Boyle, M. Azuma and T. R. Shearer, Involvement of cysteine proteases in bfgf-induced angiogenesis in guinea pig and rat cornea, J Ocul Pharmacol Ther 16(3), 271–283 (2000).
K. Hamano, T. S. Li, T. Kobayashi, S. Kobayashi, M. Matsuzaki and K. Esato, Angiogenesis induced by the implantation of self-bone marrow cells: A new material for therapeutic angiogenesis, Cell Transplant 9(3), 439–443 (2000).
G. A. Fournier, G. A. Lutty, S. Watt, A. Fenselau and A. Patz, A corneal micropocket assay for angiogenesis in the rat eye, Invest Ophthalmol Vis Sci 21(2), 351–354 (1981).
M. Chopp and Y. Li, Treatment of neural injury with marrow stromal cells, Lancet Neurol 1(2), 92–100 (2002).
Z. G. Zhang, L. Zhang, W. Tsang, H. Soltanian-Zadeh, D. Morris, R. Zhang, A. Goussev, C. Powers, T. Yeich and M. Chopp, Correlation of vegf and angiopoietin expression with disruption of bloodbrain barrier and angiogenesis after focal cerebral ischemia, J Cereb Blood Flow Metab 22(4), 379–392 (2002).
Z. G. Zhang, W. Tsang, L. Zhang, C. Powers and M. Chopp, Up-regulation of neuropilin-1 in neovasculature after focal cerebral ischemia in the adult rat, J Cereb Blood Flow Metab 21(5), 541–549 (2001).
M. M. Poo, Neurotrophins as synaptic modulators, Nat Rev Neurosci 2(1), 24–32 (2001).
S. Cohen-Cory, The developing synapse: Construction and modulation of synaptic structures and circuits, Science 298(5594), 770–776 (2002).
D. T. Theodosis and D. A. Poulain, Contribution of astrocytes to activity-dependent structural plasticity in the adult brain, pp175–182 Kluwer Academic / Plenum Publishers, New York, (1999).
R. D. Fields and B. Stevens-Graham, New insights into neuron-glia communication, Science 298(5593), 556–562 (2002).
J. P. Kelly, Principles of neural science, Elsevier, Nw York, (1985).
R. J. McKeon, A. Hoke and J. Silver, Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars, Exp Neurol 136(1), 32–43 (1995).
J. Fok-Seang, N. A. DiProspero, S. Meiners, E. Muir and J. W. Fawcett, Cytokine-induced changes in the ability of astrocytes to support migration of oligodendrocyte precursors and axon growth, Eur J Neurosci 10(7), 2400–2415 (1998).
N. G. Gourmala, S. Limonta, D. Bochelen, A. Sauter and H. W. Boddeke, Localization of macrophage inflammatory protein: Macrophage inflammatory protein-1 expression in rat brain after peripheral administration of lipopolysaccharide and focal cerebral ischemia, Neuroscience 88(4), 1255–1266 (1999).
V. Darsalia, U. Heldmann, O. Lindvall and Z. Kokaia, Stroke-induced neurogenesis in aged brain, Stroke 36(8): 1790–1795 (2005).
R. J. Lichtenwalner and J. M. Parent, Adult neurogenesis and the ischemic forebrain, J Cereb Blood Flow Metab Advance online publication 15 June (2005).
P. M. Rossini and G. Dal Forno, Neuronal post-stroke plasticity in the adult, Restor Neurol Neurosci 22(3–5), 193–206 (2004).
S. B. Frost, S. Barbay, K. M. Friel, E. J. Plautz and R. J. Nudo, Reorganization of remote cortical regions after ischemic brain injury: A potential substrate for stroke recovery, J Neurophysiol 89(6), 3205–3214 (2003).
Y. Li, J. Chen and M. Chopp, Cell proliferation and differentiation from ependymal, subependymal and choroid plexus cells in response to stroke in rats, J Neurol Sci 193(2), 137–146 (2002).
R. L. Zhang, Z. G. Zhang, L. Zhang and M. Chopp, Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia, Neuroscience 105(1), 33–41 (2001).
R. L. Zhang, L. Zhang, Z. G. Zhang, D. Morris, Q. Jiang, L. Wang, L. J. Zhang and M. Chopp, Migration and differentiation of adult rat subventricular zone progenitor cells transplanted into the adult rat striatum, Neuroscience 116(2), 373–382 (2003).
R. Zhang, Z. Zhang, C. Zhang, L. Zhang, A. Robin, Y. Wang, M. Lu and M. Chopp, Stroke transiently increases subventricular zone cell division from asymmetric to symmetric and increases neuronal differentiation in the adult rat, J Neurosci 24(25), 5810–5815 (2004).
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Chopp, M., Li, Y. (2006). Transplantation of Bone Marrow Stromal Cells for Treatment of Central Nervous System Diseases. In: Fisher, J.P. (eds) Tissue Engineering. Advances in Experimental Medicine and Biology, vol 585. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-34133-0_4
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