Human Mesenchymal Stem Cells Prolong Survival and Ameliorate Motor Deficit Through Trophic Support in Huntington's Disease Mouse Models

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Aug 19

PMID 21850243

Citations 54

Authors

Yuan-Ta Lin

Yijuang Chern

Che-Kun James Shen

Hsin-Lan Wen

Ya-Chin Chang

Hung Li

Tzu-Hao Cheng

Hsiu Mei Hsieh-Li

Affiliations

Soon will be listed here.

Abstract

We investigated the therapeutic potential of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in Huntington's disease (HD) mouse models. Ten weeks after intrastriatal injection of quinolinic acid (QA), mice that received hBM-MSC transplantation showed a significant reduction in motor function impairment and increased survival rate. Transplanted hBM-MSCs were capable of survival, and inducing neural proliferation and differentiation in the QA-lesioned striatum. In addition, the transplanted hBM-MSCs induced microglia, neuroblasts and bone marrow-derived cells to migrate into the QA-lesioned region. Similar results were obtained in R6/2-J2, a genetically-modified animal model of HD, except for the improvement of motor function. After hBM-MSC transplantation, the transplanted hBM-MSCs may integrate with the host cells and increase the levels of laminin, Von Willebrand Factor (VWF), stromal cell-derived factor-1 (SDF-1), and the SDF-1 receptor Cxcr4. The p-Erk1/2 expression was increased while Bax and caspase-3 levels were decreased after hBM-MSC transplantation suggesting that the reduced level of apoptosis after hBM-MSC transplantation was of benefit to the QA-lesioned mice. Our data suggest that hBM-MSCs have neural differentiation improvement potential, neurotrophic support capability and an anti-apoptotic effect, and may be a feasible candidate for HD therapy.

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References

Chindewa R, Lapanantasin S, Sanvarinda Y, Chongthammakun S . Pueraria mirifica, phytoestrogen-induced change in synaptophysin expression via estrogen receptor in rat hippocampal neuron. J Med Assoc Thai. 2008; 91(2):208-14. View

Ramaswamy S, Shannon K, Kordower J . Huntington's disease: pathological mechanisms and therapeutic strategies. Cell Transplant. 2007; 16(3):301-12. DOI: 10.3727/000000007783464687. View

Snyder B, Chiu A, Prockop D, Chan A . Human multipotent stromal cells (MSCs) increase neurogenesis and decrease atrophy of the striatum in a transgenic mouse model for Huntington's disease. PLoS One. 2010; 5(2):e9347. PMC: 2825266. DOI: 10.1371/journal.pone.0009347. View

Wu J, Sun Z, Sun H, Wu J, Weisel R, Keating A . Intravenously administered bone marrow cells migrate to damaged brain tissue and improve neural function in ischemic rats. Cell Transplant. 2008; 16(10):993-1005. View

Ohab J, Fleming S, Blesch A, Carmichael S . A neurovascular niche for neurogenesis after stroke. J Neurosci. 2006; 26(50):13007-16. PMC: 6674957. DOI: 10.1523/JNEUROSCI.4323-06.2006. View

Yanagawa Y, Iwabuchi K, Onoe K . Enhancement of stromal cell-derived factor-1alpha-induced chemotaxis for CD4/8 double-positive thymocytes by fibronectin and laminin in mice. Immunology. 2001; 104(1):43-9. PMC: 1783275. DOI: 10.1046/j.1365-2567.2001.01292.x. View

Strauss S, Otten U, Joggerst B, Pluss K, Volk B . Increased levels of nerve growth factor (NGF) protein and mRNA and reactive gliosis following kainic acid injection into the rat striatum. Neurosci Lett. 1994; 168(1-2):193-6. DOI: 10.1016/0304-3940(94)90448-0. View

Lazic S, Grote H, Blakemore C, Hannan A, Dellen A, Phillips W . Neurogenesis in the R6/1 transgenic mouse model of Huntington's disease: effects of environmental enrichment. Eur J Neurosci. 2006; 23(7):1829-38. DOI: 10.1111/j.1460-9568.2006.04715.x. View

Kremer B, Goldberg P, Andrew S, Theilmann J, Telenius H, Zeisler J . A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med. 1994; 330(20):1401-6. DOI: 10.1056/NEJM199405193302001. View

10.

Hernandez-Lopez C, Valencia J, Hidalgo L, Martinez V, Zapata A, Sacedon R . CXCL12/CXCR4 signaling promotes human thymic dendritic cell survival regulating the Bcl-2/Bax ratio. Immunol Lett. 2008; 120(1-2):72-8. DOI: 10.1016/j.imlet.2008.07.006. View

11.

Kasper G, Dankert N, Tuischer J, Hoeft M, Gaber T, Glaeser J . Mesenchymal stem cells regulate angiogenesis according to their mechanical environment. Stem Cells. 2007; 25(4):903-10. DOI: 10.1634/stemcells.2006-0432. View

12.

Shyu W, Liu D, Lin S, Li W, Su C, Chang Y . Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke. J Clin Invest. 2008; 118(7):2482-95. PMC: 2398740. DOI: 10.1172/JCI34363. View

13.

Shyu W, Lin S, Chiang M, Su C, Li H . Intracerebral peripheral blood stem cell (CD34+) implantation induces neuroplasticity by enhancing beta1 integrin-mediated angiogenesis in chronic stroke rats. J Neurosci. 2006; 26(13):3444-53. PMC: 6673856. DOI: 10.1523/JNEUROSCI.5165-05.2006. View

14.

Kamihata H, Matsubara H, Nishiue T, Fujiyama S, Tsutsumi Y, Ozono R . Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines. Circulation. 2001; 104(9):1046-52. DOI: 10.1161/hc3501.093817. View

15.

Acarin L, Gonzalez B, Castellano B . Neuronal, astroglial and microglial cytokine expression after an excitotoxic lesion in the immature rat brain. Eur J Neurosci. 2000; 12(10):3505-20. DOI: 10.1046/j.1460-9568.2000.00226.x. View

16.

Stumm R, Zhou C, Ara T, Lazarini F, Dubois-Dalcq M, Nagasawa T . CXCR4 regulates interneuron migration in the developing neocortex. J Neurosci. 2003; 23(12):5123-30. PMC: 6741192. View

17.

Reuter I, Tai Y, Pavese N, Chaudhuri K, Mason S, Polkey C . Long-term clinical and positron emission tomography outcome of fetal striatal transplantation in Huntington's disease. J Neurol Neurosurg Psychiatry. 2008; 79(8):948-51. DOI: 10.1136/jnnp.2007.142380. View

18.

Alberti E, Los M, Garcia R, Fraga J, Serrano T, Hernandez E . Prolonged survival and expression of neural markers by bone marrow-derived stem cells transplanted into brain lesions. Med Sci Monit. 2009; 15(2):BR47-54. View

19.

Fuchs E, Tumbar T, Guasch G . Socializing with the neighbors: stem cells and their niche. Cell. 2004; 116(6):769-78. DOI: 10.1016/s0092-8674(04)00255-7. View

20.

Robin A, Zhang Z, Wang L, Zhang R, Katakowski M, Zhang L . Stromal cell-derived factor 1alpha mediates neural progenitor cell motility after focal cerebral ischemia. J Cereb Blood Flow Metab. 2005; 26(1):125-34. DOI: 10.1038/sj.jcbfm.9600172. View