Stem cell-based therapies for stroke have expanded substantially over the last decade. The diversity of embryonic and adult tissue sources provides researchers with the ability to harvest an ample supply of stem cells. However, the optimal conditions of stem cell use are still being determined. Along this line of the need for optimization studies, we discuss studies that demonstrate effective dose, timing, and route of stem cells. We recognize that stem cell derivations also provide uniquely individual difficulties and limitations in their therapeutic applications. This review will outline the current knowledge, including benefits and challenges, of the many current sources of stem cells for stroke therapy.
References
[1]
Willing, A.E.; Lixian, J.; Milliken, M.; Poulos, S.; Zigova, T.; Song, S.; Hart, C.; Sanchez-Ramos, J.; Sanberg, P.R. Intravenous versus intrastriatal cord blood administration in a rodent model of stroke. J. Neurosci. Res. 2003, 73, 296–307, doi:10.1002/jnr.10659.
[2]
Vendrame, M.; Cassady, J.; Newcomb, J.; Butler, T.; Pennypacker, K.R.; Zigova, T.; Sanberg, C.D.; Sanberg, P.R.; Willing, A.E. Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral deficits and reduces infarct volume. Stroke 2004, 35, 2390–2395, doi:10.1161/01.STR.0000141681.06735.9b.
Erlandsson, A.; Lin, C.H.; Yu, F.; Morshead, C.M. Immunosuppression promotes endogenous neural stem and progenitor cell migration and tissue regeneration after ischemic injury. Exp. Neurol. 2011, 230, 48–57, doi:10.1016/j.expneurol.2010.05.018.
[5]
Saino, O.; Taguchi, A.; Nakagomi, T.; Nakano-Doi, A.; Kashiwamura, S.; Doe, N.; Nakagomi, N.; Soma, T.; Yoshikawa, H.; Stern, D.M.; et al. Immunodeficiency reduces neural stem/progenitor cell apoptosis and enhances neurogenesis in the cerebral cortex after stroke. J. Neurosci. Res. 2010, 88, 2385–2397.
[6]
Willing, A.E.; Eve, D.J.; Sanberg, P.R. Umbilical cord blood transfusions for prevention of progressive brain injury and induction of neural recovery: An immunological perspective. Regen. Med. 2007, 2, 457–464, doi:10.2217/17460751.2.4.457.
[7]
Hunt, J.S.; Petroff, M.G.; McIntire, R.H.; Ober, C. HLA-G and immune tolerance in pregnancy. FASEB J. 2005, 19, 681–693, doi:10.1096/fj.04-2078rev.
[8]
Menier, C.; Rouas-Freiss, N.; Favier, B.; LeMaoult, J.; Moreau, P.; Carosella, E.D. Recent advances on the non-classical major histocompatibility complex class I HLA-G molecule. Tissue Antigens 2010, 75, 201–206.
[9]
Lee, J.M.; Jung, J.; Lee, H.J.; Jeong, S.J.; Cho, K.J.; Hwang, S.G.; Kim, G.J. Comparison of immunomodulatory effects of placenta mesenchymal stem cells with bone marrow and adipose mesenchymal stem cells. Int. Immunopharmacol. 2012, 13, 219–224, doi:10.1016/j.intimp.2012.03.024.
[10]
Fazekasova, H.; Lechler, R.; Langford, K.; Lombardi, G. Placenta-derived MSCs are partially immunogenic and less immunomodulatory than bone marrow-derived MSCs. J. Tissue Eng. Regen. Med. 2011, 5, 684–694, doi:10.1002/term.362.
[11]
Huang, H.; Chen, L.; Sanberg, P. Cell Therapy from Bench to Bedside Translation in CNS Neurorestoratology Era. Cell Med. 2010, 1, 15–46, doi:10.3727/215517910X516673.
[12]
Asano, T.; Ageyama, N.; Takeuchi, K.; Momoeda, M.; Kitano, Y.; Sasaki, K.; Ueda, Y.; Suzuki, Y.; Kondo, Y.; Torii, R.; et al. Engraftment and tumor formation after allogeneic in utero transplantation of primate embryonic stem cells. Transplantation 2003, 76, 1061–1067, doi:10.1097/01.TP.0000090342.85649.81.
[13]
Riess, P.; Molcanyi, M.; Bentz, K.; Maegele, M.; Simanski, C.; Carlitscheck, C.; Schneider, A.; Hescheler, J.; Bouillon, B.; Schafer, U.; Neugebauer, E. Embryonic stem cell transplantation after experimental traumatic brain injury dramatically improves neurological outcome, but may cause tumors. J. Neurotrauma 2007, 24, 216–225, doi:10.1089/neu.2006.0141.
[14]
Hayashi, J.; Takagi, Y.; Fukuda, H.; Imazato, T.; Nishimura, M.; Fujimoto, M.; Takahashi, J.; Hashimoto, N.; Nozaki, K. Primate embryonic stem cell-derived neuronal progenitors transplanted into ischemic brain. J. Cereb. Blood Flow Metab. 2006, 26, 906–914, doi:10.1038/sj.jcbfm.9600247.
[15]
Oyamada, N.; Itoh, H.; Sone, M.; Yamahara, K.; Miyashita, K.; Park, K.; Taura, D.; Inuzuka, M.; Sonoyama, T.; Tsujimoto, H.; et al. Transplantation of vascular cells derived from human embryonic stem cells contributes to vascular regeneration after stroke in mice. J. Transl. Med. 2008, 6, 54, doi:10.1186/1479-5876-6-54.
[16]
Daadi, M.M.; Maag, A.L.; Steinberg, G.K. Adherent Self-Renewable Human Embryonic Stem Cell-Derived Neural Stem Cell Line: Functional Engraftment in Experimental Stroke Model. PloS One 2008, 3, e1644.
Pignataro, G.; Studer, F.E.; Wilz, A.; Simon, R.P.; Boison, D. Neuroprotection in ischemic mouse brain induced by stem cell-derived brain implants. J. Cereb. Blood Flow Metab. 2007, 27, 919–927.
[19]
Li, Z.; McKercher, S.R.; Cui, J.; Nie, Z.G.; Soussou, W.; Roberts, A.J.; Sallmen, T.; Lipton, J.H.; Talantova, M.; Okamoto, S.I.; Lipton, S.A. Myocyte enhancer factor 2C as a neurogenic and antiapoptotic transcription factor in murine embryonic stem cells. J. Neurosci. 2008, 28, 6557–6568, doi:10.1523/JNEUROSCI.0134-08.2008.
[20]
Yanagisawa, D.; Qi, M.; Kim, D.H.; Kitamura, Y.; Inden, M.; Tsuchiya, D.; Takata, K.; Taniguchi, T.; Yoshimoto, K.; Shimoama, S.; et al. Improvement of focal ischemia-induced rat dopaminergic dysfunction by striatal transplantation of mouse embryonic stem cells. Neurosci. Lett. 2006, 407, 74–79, doi:10.1016/j.neulet.2006.08.007.
[21]
Theus, M.H.; Wei, L.; Cui, L.; Francis, K.; Hu, X.Y.; Keogh, C.; Yu, S.P. In vitro hypoxic preconditioning of embryonic stem cells as a strategy of promoting cell survival and functional benefits after transplantation into the ischemic rat brain. Exp. Neurol. 2008, 210, 656–670, doi:10.1016/j.expneurol.2007.12.020.
[22]
Yang, T.; Tsang, K.S.; Poon, W.S.; Ng, H.K. Neurotrophism of Bone Marrow Stromal Cells to Embryonic Stem Cells: Noncontact Induction and Transplantation to a Mouse Ischemic Stroke Model. Cell Transplant. 2009, 18, 391–404, doi:10.3727/096368909788809767.
[23]
Borlongan, C.V.; Glover, L.E.; Tajiri, N.; Kaneko, Y.; Freeman, T.B. The great migration of bone marrow-derived stem cells toward the ischemic brain: Therapeutic implications for stroke and other neurological disorders. Prog. Neurobiol. 2011, 95, 213–228, doi:10.1016/j.pneurobio.2011.08.005.
Krause, D.S.; Ito, T.; Fackler, M.J.; Smith, O.M.; Collector, M.I.; Sharkis, S.J.; May, W.S. Characterization of murine CD34, a marker for hematopoietic progenitor and stem cells. Blood 1994, 84, 691–701.
[26]
Kiel, M.J.; Yilmaz, O.H.; Iwashita, T.; Terhorst, C.; Morrison, S.J. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 2005, 121, 1109–1121, doi:10.1016/j.cell.2005.05.026.
[27]
Lapidot, T.; Dar, A.; Kollet, O. How do stem cells find their way home? Blood 2005, 106, 1901–1910, doi:10.1182/blood-2005-04-1417.
[28]
Lapidot, T.; Kollet, O. The brain-bone-blood triad: Traffic lights for stem-cell homing and mobilization. Hematology Am. Soc. Hematol. Educ. Program 2010, 2010, 1–6, doi:10.1182/asheducation-2010.1.1.
[29]
Nervi, B.; Link, D.C.; DiPersio, J.F. Cytokines and hematopoietic stem cell mobilization. J. Cell. Biochem. 2006, 99, 690–705, doi:10.1002/jcb.21043.
[30]
Papayannopoulou, T.; Scadden, D.T. Stem-cell ecology and stem cells in motion. Blood 2008, 111, 3923–3930, doi:10.1182/blood-2007-08-078147.
[31]
Kalinkovich, A.; Spiegel, A.; Shivtiel, S.; Kollet, O.; Jordaney, N.; Piacibello, W.; Lapidot, T. Blood-forming stem cells are nervous: Direct and indirect regulation of immature human CD34+ cells by the nervous system. Brain Behav. Immun. 2009, 23, 1059–1065, doi:10.1016/j.bbi.2009.03.008.
[32]
Hennemann, B.; Ickenstein, G.; Sauerbruch, S.; Luecke, K.; Haas, S.; Horn, M.; Andreesen, R.; Bogdahn, U.; Winkler, J. Mobilization of CD34+ hematopoietic cells, colony-forming cells and long-term culture-initiating cells into the peripheral blood of patients with an acute cerebral ischemic insult. Cytotherapy 2008, 10, 303–311, doi:10.1080/14653240801949994.
[33]
Dunac, A.; Frelin, C.; Popolo-Blondeau, M.; Chatel, M.; Mahagne, M.H.; Philip, P.J. Neurological and functional recovery in human stroke are associated with peripheral blood CD34+ cell mobilization. J. Neurol. 2007, 254, 327–332, doi:10.1007/s00415-006-0362-1.
[34]
Moniche, F.; Gonzalez, A.; Gonzalez-Marcos, J.R.; Carmona, M.; Pinero, P.; Espigado, I.; Garcia-Solis, D.; Cayuela, A.; Montaner, J.; Boada, C.; et al. Intra-Arterial Bone Marrow Mononuclear Cells in Ischemic Stroke A Pilot Clinical Trial. Stroke 2012, 43, U2242–U2244, doi:10.1161/STROKEAHA.112.659409.
[35]
Savitz, S.I.; Misra, V.; Kasam, M.; Juneja, H.; Cox, C.S.; Alderman, S.; Aisiku, I.; Kar, S.; Gee, A.; Grotta, J.C. Intravenous Autologous Bone Marrow Mononuclear Cells for Ischemic Stroke. Ann. Neurol. 2011, 70, 59–69, doi:10.1002/ana.22458.
[36]
Battistella, V.; de Freitas, G.R.; da Fonseca, L.M.B.; Mercante, D.; Gutfilen, B.; Goldenberg, R.C.; Dias, J.V.; Kasai-Brunswick, T.H.; Wajnberg, E.; Rosado-de-Castro, P.H.; et al. Safety of autologous bone marrow mononuclear cell transplantation in patients with nonacute ischemic stroke. Regen. Med. 2011, 6, 45–52, doi:10.2217/rme.10.97.
[37]
Friedrich, M.A.G.; Martins, M.P.; Araujo, M.D.; Klamt, C.; Vedolin, L.; Garicochea, B.; Raupp, E.F.; El Ammar, J.S.; Machado, D.C.; da Costa, J.C.; et al. Intra-Arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Patients With Moderate to Severe Middle Cerebral Artery Acute Ischemic Stroke. Cell Transplant. 2012, 21, S13–S21, doi:10.3727/096368912X612512.
[38]
Zimmermann, S.; Voss, M.; Kaiser, S.; Kapp, U.; Waller, C.F.; Martens, U.M. Lack of telomerase activity in human mesenchymal stem cells. Leukemia 2003, 17, 1146–1149, doi:10.1038/sj.leu.2402962.
[39]
Chopp, M.; Li, Y. Treatment of neural injury with marrow stromal cells. Lancet Neurol. 2002, 1, 92–100, doi:10.1016/S1474-4422(02)00040-6.
[40]
Rempe, D.A.; Kent, T.A. Using bone marrow stromal cells for treatment of stroke. Neurology 2002, 59, 486–487, doi:10.1212/WNL.59.4.486.
[41]
Song, S.; Kamath, S.; Mosquera, D.; Zigova, T.; Sanberg, P.; Vesely, D.L.; Sanchez-Ramos, J. Expression of brain natriuretic peptide by human bone marrow stromal cells. Exp. Neurol. 2004, 185, 191–197, doi:10.1016/j.expneurol.2003.09.003.
[42]
Chen, J.; Li, Y.; Wang, L.; Lu, M.; Chopp, M. Caspase inhibition by Z-VAD increases the survival of grafted bone marrow cells and improves functional outcome after MCAo in rats. J. Neurol. Sci. 2002, 199, 17–24, doi:10.1016/S0022-510X(02)00075-8.
[43]
Chen, J.; Li, Y.; Katakowski, M.; Chen, X.; Wang, L.; Lu, D.; Lu, M.; Gautam, S.C.; Chopp, M. Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. J. Neurosci. Res. 2003, 73, 778–786, doi:10.1002/jnr.10691.
[44]
Li, Y.; Chen, J.; Wang, L.; Lu, M.; Chopp, M. Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology 2001, 56, 1666–1672, doi:10.1212/WNL.56.12.1666.
[45]
Zhang, J.; Li, Y.; Chen, J.; Yang, M.; Katakowski, M.; Lu, M.; Chopp, M. Expression of insulin-like growth factor 1 and receptor in ischemic rats treated with human marrow stromal cells. Brain Res. 2004, 1030, 19–27, doi:10.1016/j.brainres.2004.09.061.
[46]
Crigler, L.; Robey, R.C.; Asawachaicharn, A.; Gaupp, D.; Phinney, D.G. Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp. Neurol. 2006, 198, 54–64, doi:10.1016/j.expneurol.2005.10.029.
[47]
Lin, R.Z.; Moreno-Luna, R.; Zhou, B.; Pu, W.T.; Melero-Martin, J.M. Equal modulation of endothelial cell function by four distinct tissue-specific mesenchymal stem cells. Angiogenesis 2012, 15, 443–455, doi:10.1007/s10456-012-9272-2.
[48]
Bang, O.Y.; Lee, J.S.; Lee, P.H.; Lee, G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann. Neurol. 2005, 57, 874–882, doi:10.1002/ana.20501.
[49]
Lee, J.S.; Hong, J.M.; Moon, G.J.; Lee, P.H.; Ahn, Y.H.; Bang, O.Y.; Collaborators, S. A Long-Term Follow-Up Study of Intravenous Autologous Mesenchymal Stem Cell Transplantation in Patients with Ischemic Stroke. Stem Cells 2010, 28, 1099–1106, doi:10.1002/stem.430.
[50]
Dominici, M.; Le Blanc, K.; Mueller, I.; Slaper-Cortenbach, I.; Marini, F.; Krause, D.; Deans, R.; Keating, A.; Prockop, D.; Horwitz, E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006, 8, 315–317, doi:10.1080/14653240600855905.
[51]
Barlow, S.; Brooke, G.; Chatterjee, K.; Price, G.; Pelekanos, R.; Rossetti, T.; Doody, M.; Venter, D.; Pain, S.; Gilshenan, K.; Atkinson, K. Comparison of human placenta- and bone marrow-derived multipotent mesenchymal stem cells. Stem Cells Dev. 2008, 17, 1095–1107, doi:10.1089/scd.2007.0154.
Kim, S.H.; Kim, Y.S.; Lee, S.Y.; Kim, K.H.; Lee, Y.M.; Kim, W.K.; Lee, Y.K. Gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow. J. Periodontal Implant Sci. 2011, 41, 192–200, doi:10.5051/jpis.2011.41.4.192.
[54]
Dmitrieva, R.I.; Minullina, I.R.; Bilibina, A.A.; Tarasova, O.V.; Anisimov, S.V.; Zaritskey, A.Y. Bone marrow- and subcutaneous adipose tissue-derived mesenchymal stem cells: Differences and similarities. Cell Cycle 2012, 11, 377–383, doi:10.4161/cc.11.2.18858.
[55]
Strioga, M.; Viswanathan, S.; Darinskas, A.; Slaby, O.; Michalek, J. Same or Not the Same? Comparison of Adipose Tissue-Derived versus Bone Marrow-Derived Mesenchymal Stem and Stromal Cells. Stem Cells Dev. 2012, 21, 2724–2752, doi:10.1089/scd.2011.0722.
[56]
Vidal, M.A.; Walker, N.J.; Napoli, E.; Borjesson, D.L. Evaluation of senescence in mesenchymal stem cells isolated from equine bone marrow, adipose tissue, and umbilical cord tissue. Stem Cells Dev. 2012, 21, 273–283, doi:10.1089/scd.2010.0589.
De Luca, A.; Lamura, L.; Gallo, M.; Maffia, V.; Normanno, N. Mesenchymal stem cell-derived interleukin-6 and vascular endothelial growth factor promote breast cancer cell migration. J. Cell. Biochem. 2012, 113, 3363–3370, doi:10.1002/jcb.24212.
Subramanian, A.; Shu-Uin, G.; Kae-Siang, N.; Gauthaman, K.; Biswas, A.; Choolani, M.; Bongso, A.; Chui-Yee, F. Human umbilical cord Wharton’s jelly mesenchymal stem cells do not transform to tumor-associated fibroblasts in the presence of breast and ovarian cancer cells unlike bone marrow mesenchymal stem cells. J. Cell. Biochem. 2012, 113, 1886–1895, doi:10.1002/jcb.24057.
Urbich, C.; Dimmeler, S. Endothelial progenitor cells: Characterization and role in vascular biology. Circ. Res. 2004, 95, 343–353, doi:10.1161/01.RES.0000137877.89448.78.
[63]
Asahara, T.; Murohara, T.; Sullivan, A.; Silver, M.; van der Zee, R.; Li, T.; Witzenbichler, B.; Schatteman, G.; Isner, J.M. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997, 275, 964–967, doi:10.1126/science.275.5302.964.
Masuda, H.; Asahara, T. Post-natal endothelial progenitor cells for neovascularization in tissue regeneration. Cardiovasc. Res. 2003, 58, 390–398, doi:10.1016/S0008-6363(02)00785-X.
[66]
Yip, H.K.; Chang, L.T.; Chang, W.N.; Lu, C.H.; Liou, C.W.; Lan, M.Y.; Liu, J.S.; Youssef, A.A.; Chang, H.W. Level and value of circulating endothelial progenitor cells in patients after acute ischemic stroke. Stroke 2008, 39, 69–74, doi:10.1161/STROKEAHA.107.489401.
[67]
Chen, J.; Chen, S.Z.; Chen, Y.S.; Zhang, C.; Wang, J.J.; Zhang, W.F.; Liu, G.; Zhao, B.; Chen, Y.F. Circulating endothelial progenitor cells and cellular membrane microparticles in db/db diabetic mouse: Possible implications in cerebral ischemic damage. Am. J. Physiol. Endocrinol. Metab. 2011, 301, E62–E71, doi:10.1152/ajpendo.00026.2011.
[68]
Chen, Z.Z.; Jiang, X.D.; Zhang, L.L.; Shang, J.H.; Du, M.X.; Xu, G.; Xu, R.X. Beneficial effect of autologous transplantation of bone marrow stromal cells and endothelial progenitor cells on cerebral ischemia in rabbits. Neurosci. Lett. 2008, 445, 36–41, doi:10.1016/j.neulet.2008.08.039.
[69]
Kucia, M.; Reca, R.; Campbell, F.R.; Zuba-Surma, E.; Majka, M.; Ratajczak, J.; Ratajczak, M.Z. A population of very small embryonic-like (VSEL) CXCR4+SSEA-1+Oct-4+ stem cells identified in adult bone marrow. Leukemia 2006, 20, 857–869, doi:10.1038/sj.leu.2404171.
[70]
Kucia, M.; Zhang, Y.P.; Reca, R.; Wysoczynski, M.; Machalinski, B.; Majka, M.; Ildstad, S.T.; Ratajczak, J.; Shields, C.B.; Ratajczak, M.Z. Cells enriched in markers of neural tissue-committed stem cells reside in the bone marrow and are mobilized into the peripheral blood following stroke. Leukemia 2006, 20, 18–28, doi:10.1038/sj.leu.2404011.
[71]
Ratajczak, M.Z.; Kim, C.H.; Wojakowski, W.; Janowska-Wieczorek, A.; Kucia, M.; Ratajczak, J. Innate immunity as orchestrator of stem cell mobilization. Leukemia 2010, 24, 1667–1675, doi:10.1038/leu.2010.162.
[72]
Paczkowska, E.; Kucia, M.; Koziarska, D.; Halasa, M.; Safranow, K.; Masiuk, M.; Karbicka, A.; Nowik, M.; Nowacki, P.; Ratajczak, M.Z.; Machalinski, B. Clinical Evidence That Very Small Embryonic-Like Stem Cells Are Mobilized Into Peripheral Blood in Patients After Stroke. Stroke 2009, 40, 1237–1244, doi:10.1161/STROKEAHA.108.535062.
[73]
Ratajczak, M.Z.; Machalinski, B.; Wojakowski, W.; Ratajczak, J.; Kucia, M. A hypothesis for an embryonic origin of pluripotent Oct-4+ stem cells in adult bone marrow and other tissues. Leukemia 2007, 21, 860–867.
[74]
Kucia, M.; Wysoczynski, M.; Ratajczak, J.; Ratajczak, M.Z. Identification of very small embryonic like (VSEL) stem cells in bone marrow. Cell Tissue Res. 2008, 331, 125–134, doi:10.1007/s00441-007-0485-4.
[75]
Kucia, M.; Ratajczak, J.; Ratajczak, M.Z. Are bone marrow stem cells plastic or heterogenous—that is the question. Exp. Hematol. 2005, 33, 613–623, doi:10.1016/j.exphem.2005.01.016.
[76]
Zuba-Surma, E.K.; Kucia, M.; Wu, W.; Klich, I.; Lillard, J.W., Jr.; Ratajczak, J.; Ratajczak, M.Z. Very small embryonic-like stem cells are present in adult murine organs: ImageStream-based morphological analysis and distribution studies. Cytometry A 2008, 73A, 1116–1127, doi:10.1002/cyto.a.20667.
[77]
Ratajczak, J.; Shin, D.M.; Wan, W.; Liu, R.; Masternak, M.M.; Piotrowska, K.; Wiszniewska, B.; Kucia, M.; Bartke, A.; Ratajczak, M.Z. Higher number of stem cells in the bone marrow of circulating low Igf-1 level Laron dwarf mice—novel view on Igf-1, stem cells and aging. Leukemia 2011, 25, 729–733, doi:10.1038/leu.2010.314.
[78]
Nakayama, D.; Matsuyama, T.; Ishibashi-Ueda, H.; Nakagomi, T.; Kasahara, Y.; Hirose, H.; Kikuchi-Taura, A.; Stern, D.M.; Mori, H.; Taguchi, A. Injury-induced neural stem/progenitor cells in post-stroke human cerebral cortex. Eur. J. Neurosci. 2010, 31, 90–98, doi:10.1111/j.1460-9568.2009.07043.x.
[79]
Jin, K.; Sun, Y.J.; Xie, L.; Peel, A.; Mao, X.O.; Batteur, S.; Greenberg, D.A. Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum. Mol. Cell. Neurosci. 2003, 24, 171–189, doi:10.1016/S1044-7431(03)00159-3.
[80]
Thored, P.; Wood, J.; Arvidsson, A.; Cammenga, J.; Kokaia, Z.; Lindvall, O. Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke. Stroke 2007, 38, 3032–3039, doi:10.1161/STROKEAHA.107.488445.
[81]
Kojima, T.; Hirota, Y.; Ema, M.; Takahashi, S.; Miyoshi, I.; Okano, H.; Sawamoto, K. Subventricular zone-derived neural progenitor cells migrate along a blood vessel scaffold toward the post-stroke striatum. Stem Cells 2010, 28, 545–554.
[82]
Barkho, B.Z.; Munoz, A.E.; Li, X.; Li, L.; Cunningham, L.A.; Zhao, X. Endogenous matrix metalloproteinase (MMP)-3 and MMP-9 promote the differentiation and migration of adult neural progenitor cells in response to chemokines. Stem Cells 2008, 26, 3139–3149, doi:10.1634/stemcells.2008-0519.
[83]
Liu, X.S.; Chopp, M.; Zhang, R.L.; Hozeska-Solgot, A.; Gregg, S.C.; Buller, B.; Lu, M.; Zhang, Z.G. Angiopoietin 2 mediates the differentiation and migration of neural progenitor cells in the subventricular zone after stroke. J. Biol. Chem. 2009, 284, 22680–22689.
[84]
Zhang, R.L.; Chopp, M.; Gregg, S.R.; Toh, Y.; Roberts, C.; Letourneau, Y.; Buller, B.; Jia, L.; Davarani, S.P.N.; Zhang, Z.G. Patterns and dynamics of subventricular zone neuroblast migration in the ischemic striatum of the adult mouse. J. Cereb. Blood Flow Metab. 2009, 29, 1240–1250, doi:10.1038/jcbfm.2009.55.
[85]
Carbajal, K.S.; Schaumburg, C.; Strieter, R.; Kane, J.; Lane, T.E. Migration of engrafted neural stem cells is mediated by CXCL12 signaling through CXCR4 in a viral model of multiple sclerosis. Proc. Natl. Acad. Sci. USA 2010, 107, 11068–11073.
[86]
Deierborg, T.; Roybon, L.; Inacio, A.R.; Pesic, J.; Brundin, P. Brain injury activates microglia that induce neural stem cell proliferation ex vivo and promote differentiation of neurosphere-derived cells into neurons and oligodendrocytes. Neuroscience 2010, 171, 1386–1396, doi:10.1016/j.neuroscience.2010.09.045.
[87]
Arvidsson, A.; Collin, T.; Kirik, D.; Kokaia, Z.; Lindvall, O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat. Med. 2002, 8, 963–970.
[88]
Nygren, J.; Wieloch, T.; Pesic, J.; Brundin, P.; Deierborg, T. Enriched environment attenuates cell genesis in subventricular zone after focal ischemia in mice and decreases migration of newborn cells to the striatum. Stroke 2006, 37, 2824–2829, doi:10.1161/01.STR.0000244769.39952.90.
[89]
Deierborg, T.; Staflin, K.; Pesic, J.; Roybon, L.; Brundin, P.; Lundberg, C. Absence of striatal newborn neurons with mature phenotype following defined striatal and cortical excitotoxic brain injuries. Exp. Neurol. 2009, 219, 363–367, doi:10.1016/j.expneurol.2009.05.002.
[90]
Park, D.H.; Eve, D.J.; Sanberg, P.R.; Musso, J., III; Bachstetter, A.D.; Wolfson, A.; Schlunk, A.; Baradez, M.O.; Sinden, J.D.; Gemma, C. Increased neuronal proliferation in the dentate gyrus of aged rats following neural stem cell implantation. Stem Cells Dev. 2010, 19, 175–180, doi:10.1089/scd.2009.0172.
[91]
Jin, K.; Xie, L.; Mao, X.; Greenberg, M.B.; Moore, A.; Peng, B.; Greenberg, R.B.; Greenberg, D.A. Effect of human neural precursor cell transplantation on endogenous neurogenesis after focal cerebral ischemia in the rat. Brain Res. 2011, 1374, 56–62, doi:10.1016/j.brainres.2010.12.037.
[92]
Minnerup, J.; Kim, J.B.; Schmidt, A.; Diederich, K.; Bauer, H.; Schilling, M.; Strecker, J.K.; Ringelstein, E.B.; Sommer, C.; Scholer, H.R.; Schabitz, W.R. Effects of neural progenitor cells on sensorimotor recovery and endogenous repair mechanisms after photothrombotic stroke. Stroke 2011, 42, 1757–1763, doi:10.1161/STROKEAHA.110.599282.
[93]
Stroemer, P.; Patel, S.; Hope, A.; Oliveira, C.; Pollock, K.; Sinden, J. The Neural Stem Cell Line CTX0E03 Promotes Behavioral Recovery and Endogenous Neurogenesis after Experimental Stroke in a Dose-Dependent Fashion. Neurorehab. Neural Repair 2009, 23, 895–909, doi:10.1177/1545968309335978.
[94]
Daadi, M.M.; Li, Z.; Arac, A.; Grueter, B.A.; Sofilos, M.; Malenka, R.C.; Wu, J.C.; Steinberg, G.K. Molecular and magnetic resonance imaging of human embryonic stem cell-derived neural stem cell grafts in ischemic rat brain. Mol. Ther. 2009, 17, 1282–1291, doi:10.1038/mt.2009.104.
[95]
Chaichana, K.L.; Guerrero-Cazares, H.; Capilla-Gonzalez, V.; Zamora-Berridi, G.; Achanta, P.; Gonzalez-Perez, O.; Jallo, G.I.; Garcia-Verdugo, J.M.; Quinones-Hinojosa, A. Intra-operatively obtained human tissue: Protocols and techniques for the study of neural stem cells. J. Neurosci. Methods 2009, 180, 116–125, doi:10.1016/j.jneumeth.2009.02.014.
[96]
Jandial, R.; Snyder, E.Y. A safer stem cell: On guard against cancer. Nat. Med. 2009, 15, 999–1001, doi:10.1038/nm0909-999.
[97]
Amariglio, N.; Rechavi, G. On the origin of glioneural neoplasms after neural cell transplantation. Nat. Med. 2010, 16, 157; author reply 157–158.
[98]
Amariglio, N.; Hirshberg, A.; Scheithauer, B.W.; Cohen, Y.; Loewenthal, R.; Trakhtenbrot, L.; Paz, N.; Koren-Michowitz, M.; Waldman, D.; Leider-Trejo, L.; et al. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med. 2009, 6, e1000029.
[99]
Wu, W.; He, Q.; Li, X.; Zhang, X.; Lu, A.; Ge, R.; Zhen, H.; Chang, A.E.; Li, Q.; Shen, L. Long-term cultured human neural stem cells undergo spontaneous transformation to tumor-initiating cells. Int. J. Biol. Sci. 2011, 7, 892–901.
[100]
Newman, M.B.; Misiuta, I.; Willing, A.E.; Zigova, T.; Karl, R.C.; Borlongan, C.V.; Sanberg, P.R. Tumorigenicity issues of embryonic carcinoma-derived stem cells: Relevance to surgical trials using NT2 and hNT neural cells. Stem Cells Dev. 2005, 14, 29–43, doi:10.1089/scd.2005.14.29.
[101]
Kondziolka, D.; Steinberg, G.K.; Wechsler, L.; Meltzer, C.C.; Elder, E.; Gebel, J.; Decesare, S.; Jovin, T.; Zafonte, R.; Lebowitz, J.; et al. Neurotransplantation for patients with subcortical motor stroke: A phase 2 randomized trial. J. Neurosurg. 2005, 103, 38–45, doi:10.3171/jns.2005.103.1.0038.
[102]
Pollock, K.; Stroemer, P.; Patel, S.; Stevanato, L.; Hope, A.; Miljan, E.; Dong, Z.; Hodges, H.; Price, J.; Sinden, J.D. A conditionally immortal clonal stem cell line from human cortical neuroepithelium for the treatment of ischemic stroke. Exp. Neurol. 2006, 199, 143–155, doi:10.1016/j.expneurol.2005.12.011.
[103]
Mack, G.S. ReNeuron and StemCells get green light for neural stem cell trials. Nat. Biotechnol. 2011, 29, 95–97.
[104]
Marcus, A.J.; Woodbury, D. Fetal stem cells from extra-embryonic tissues: Do not discard. J. Cell. Mol. Med. 2008, 12, 730–742, doi:10.1111/j.1582-4934.2008.00221.x.
[105]
Yu, S.J.; Soncini, M.; Kaneko, Y.; Hess, D.C.; Parolini, O.; Borlongan, C.V. Amnion: A potent graft source for cell therapy in stroke. Cell Transplant. 2009, 18, 111–118, doi:10.3727/096368909788341243.
[106]
Diaz-Prado, S.; Muinos-Lopez, E.; Hermida-Gomez, T.; Rendal-Vazquez, M.E.; Fuentes-Boquete, I.; de Toro, F.J.; Blanco, F.J. Multilineage differentiation potential of cells isolated from the human amniotic membrane. J. Cell. Biochem. 2010, 111, 846–857.
[107]
Konig, J.; Huppertz, B.; Desoye, G.; Parolini, O.; Frohlich, J.D.; Weiss, G.; Dohr, G.; Sedlmayr, P.; Lang, I. Amnion-derived mesenchymal stromal cells show angiogenic properties but resist differentiation into mature endothelial cells. Stem Cells Dev. 2012, 21, 1309–1320, doi:10.1089/scd.2011.0223.
[108]
Yarygin, K.N.; Kholodenko, I.V.; Konieva, A.A.; Burunova, V.V.; Tairova, R.T.; Gubsky, L.V.; Cheglakov, I.B.; Pirogov, Y.A.; Yarygin, V.N.; Skvortsova, V.I. Mechanisms of positive effects of transplantation of human placental mesenchymal stem cells on recovery of rats after experimental ischemic stroke. Bull. Exp. Biol. Med. 2009, 148, 862–868.
[109]
Chen, J.; Shehadah, A.; Pal, A.; Zacharek, A.; Cui, X.; Cui, Y.; Roberts, C.; Lu, M.; Zeitlin, A.; Hariri, R.; Chopp, M. Neuroprotective effect of human placenta-derived cell treatment of stroke in rats. Cell Transplant. 2012. in press.
[110]
Kranz, A.; Wagner, D.C.; Kamprad, M.; Scholz, M.; Schmidt, U.R.; Nitzsche, F.; Aberman, Z.; Emmrich, F.; Riegelsberger, U.M.; Boltze, J. Transplantation of placenta-derived mesenchymal stromal cells upon experimental stroke in rats. Brain Res. 2010, 1315, 128–136, doi:10.1016/j.brainres.2009.12.001.
[111]
Liao, W.B.; Xie, J.; Zhong, J.; Liu, Y.J.; Du, L.; Zhou, B.; Xu, J.; Liu, P.X.; Yang, S.G.; Wang, J.M.; et al. Therapeutic Effect of Human Umbilical Cord Multipotent Mesenchymal Stromal Cells in a Rat Model of Stroke. Transplantation 2009, 87, 350–359.
[112]
Deuse, T.; Stubbendorff, M.; Tang-Quan, K.; Phillips, N.; Kay, M.A.; Eiermann, T.; Phan, T.T.; Volk, H.D.; Reichenspurner, H.; Robbins, R.C.; Schrepfer, S. Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells. Cell Transplant. 2011, 20, 655–667, doi:10.3727/096368910X536473.
[113]
Ding, D.C.; Shyu, W.C.; Chiang, M.F.; Lin, S.Z.; Chang, Y.C.; Wang, H.J.; Su, C.Y.; Li, H. Enhancement of neuroplasticity through upregulation of beta 1-integrin in human umbilical cord-derived stromal cell implanted stroke model. Neurobiol. Dis. 2007, 27, 339–353, doi:10.1016/j.nbd.2007.06.010.
[114]
Najar, M.; Raicevic, G.; Boufker, H.I.; Fayyad-Kazan, H.; De Bruyn, C.; Meuleman, N.; Bron, D.; Toungouz, M.; Lagneaux, L. Adipose-tissue-derived and Wharton’s jelly-derived mesenchymal stromal cells suppress lymphocyte responses by secreting leukemia inhibitory factor. Tissue Eng. Part A 2010, 16, 3537–3546, doi:10.1089/ten.tea.2010.0159.
[115]
Vendrame, M.; Gemma, C.; de Mesquita, D.; Collier, L.; Bickford, P.C.; Sanberg, C.D.; Sanberg, P.R.; Pennypacker, K.R.; Willing, A.E. Anti-inflammatory effects of human cord blood cells in a rat model of stroke. Stem Cells Dev. 2005, 14, 595–604, doi:10.1089/scd.2005.14.595.
[116]
Xiao, J.; Nan, Z.H.; Motooka, Y.; Low, W.C. Transplantation of a novel cell line population of umbilical cord blood stem cells ameliorates neurological deficits associated with ischemic brain injury. Stem Cells Dev. 2005, 14, 722–733, doi:10.1089/scd.2005.14.722.
Kim, J.M.; Lee, S.T.; Chu, K.; Jung, K.H.; Song, E.C.; Kim, S.J.; Sinn, D.I.; Kim, J.H.; Park, D.K.; Kang, K.M.; et al. Systemic transplantation of human adipose stem cells attenuated cerebral inflammation and degeneration in a hemorrhagic stroke model. Brain Res. 2007, 1183, 43–50.
[120]
Leu, S.; Lin, Y.C.; Yuen, C.M.; Yen, C.H.; Kao, Y.H.; Sun, C.K.; Yip, H.K. Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats. J. Transl. Med. 2010, 8, 63, doi:10.1186/1479-5876-8-63.
[121]
Ikegame, Y.; Yamashita, K.; Hayashi, S.I.; Mizuno, H.; Tawada, M.; You, F.; Yamada, K.; Tanaka, Y.; Egashira, Y.; Nakashima, S.; Yoshimura, S.I.; Iwama, T. Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy. Cytotherapy 2011, 13, 675–685, doi:10.3109/14653249.2010.549122.
[122]
Rubio, D.; Garcia-Castro, J.; Martin, M.C.; de la Fuente, R.; Cigudosa, J.C.; Lloyd, A.C.; Bernad, A. Spontaneous human adult stem cell transformation. Cancer Res. 2005, 65, 3035–3039.
[123]
de la Fuente, R.; Bernad, A.; Garcia-Castro, J.; Martin, M.C.; Cigudosa, J.C. Retraction: Spontaneous human adult stem cell transformation. Cancer Res. 2010, 70, 6682.
[124]
Ra, J.C.; Shin, I.S.; Kim, S.H.; Kang, S.K.; Kang, B.C.; Lee, H.Y.; Kim, Y.J.; Jo, J.Y.; Yoon, E.J.; Choi, H.J.; Kwon, E. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev. 2011, 20, 1297–1308, doi:10.1089/scd.2010.0466.
Hassiotou, F.; Beltran, A.; Chetwynd, E.; Stuebe, A.M.; Twigger, A.J.; Metzger, P.; Trengove, N.; Lai, C.T.; Filgueira, L.; Blancafort, P.; Hartmann, P.E. Breastmilk Is a Novel Source of Stem Cells with Multilineage Differentiation Potential. Stem Cells 2012, 30, 2164–2174, doi:10.1002/stem.1188.
[132]
McGregor, J.A.; Rogo, L.J. Breast milk: An unappreciated source of stem cells. J. Hum. Lact. 2006, 22, 270–271, doi:10.1177/0890334406290222.
[133]
Gronthos, S.; Mankani, M.; Brahim, J.; Robey, P.G.; Shi, S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc. Natl. Acad. Sci. USA 2000, 97, 13625–13630.
[134]
Seo, B.M.; Miura, M.; Gronthos, S. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 2004, 364, 149–155.
Sonoyama, W.; Liu, Y.; Yamaza, T.; Tuan, R.S.; Wang, S.; Shi, S.; Huang, G.T.J. Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: A pilot study. J. Endod. 2008, 34, 166–171, doi:10.1016/j.joen.2007.11.021.
[137]
Morsczeck, C.; Gotz, W.; Schierholz, J.; Zellhofer, F.; Kuhn, U.; Mohl, C.; Sippel, C.; Hoffmann, K.H. Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol. 2005, 24, 155–165, doi:10.1016/j.matbio.2004.12.004.
[138]
Huang, G.T.J.; Gronthos, S.; Shi, S. Mesenchymal Stem Cells Derived from Dental Tissues vs. Those from Other Sources: Their Biology and Role in Regenerative Medicine. J. Dent. Res. 2009, 88, 792–806, doi:10.1177/0022034509340867.
[139]
Miura, M.; Gronthos, S.; Zhao, M.; Lu, B.; Fisher, L.W.; Robey, P.G.; Shi, S. SHED: Stem cells from human exfoliated deciduous teeth. Proc. Natl. Acad. Sci. USA 2003, 100, 5807–5812.
[140]
Yang, K.L.; Chen, M.F.; Liao, C.H.; Pang, C.Y.; Lin, P.Y. A simple and efficient method for generating Nurr1-positive neuronal stem cells from human wisdom teeth (tNSC) and the potential of tNSC for stroke therapy. Cytotherapy 2009, 11, 606–617, doi:10.1080/14653240902806994.
Karaoz, E.; Demircan, P.C.; Saglam, O.; Aksoy, A.; Kaymaz, F.; Duruksu, G. Human dental pulp stem cells demonstrate better neural and epithelial stem cell properties than bone marrow-derived mesenchymal stem cells. Histochem. Cell Biol. 2011, 136, 455–473, doi:10.1007/s00418-011-0858-3.
[143]
Takahashi, K.; Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126, 663–676, doi:10.1016/j.cell.2006.07.024.
[144]
Cai, J.; Li, W.; Su, H.; Qin, D.; Yang, J.; Zhu, F.; Xu, J.; He, W.; Guo, X.; Labuda, K.; et al. Generation of human induced pluripotent stem cells from umbilical cord matrix and amniotic membrane mesenchymal cells. J. Biol. Chem. 2010, 285, 11227–11234.
[145]
Tat, P.A.; Sumer, H.; Jones, K.L.; Upton, K.; Verma, P.J. The efficient generation of induced pluripotent stem (iPS) cells from adult mouse adipose tissue-derived and neural stem cells. Cell Transplant. 2010, 19, 525–536, doi:10.3727/096368910X491374.
[146]
Chen, S.J.; Chang, C.M.; Tsai, S.K.; Chang, Y.L.; Chou, S.J.; Huang, S.S.; Tai, L.K.; Chen, Y.C.; Ku, H.H.; Li, H.Y.; Chiou, S.H. Functional Improvement of Focal Cerebral Ischemia Injury by Subdural Transplantation of Induced Pluripotent Stem Cells with Fibrin Glue. Stem Cells Dev. 2010, 19, 1757–1767, doi:10.1089/scd.2009.0452.
[147]
Jiang, M.; Lv, L.; Ji, H.; Yang, X.; Zhu, W.; Cai, L.; Gu, X.; Chai, C.; Huang, S.; Sun, J.; Dong, Q. Induction of pluripotent stem cells transplantation therapy for ischemic stroke. Mol. Cell. Biochem. 2011, 354, 67–75, doi:10.1007/s11010-011-0806-5.
[148]
Zhao, T.; Zhang, Z.N.; Rong, Z.; Xu, Y. Immunogenicity of induced pluripotent stem cells. Nature 2011, 474, 212–215, doi:10.1038/nature10135.
[149]
Kawai, H.; Yamashita, T.; Ohta, Y.; Deguchi, K.; Nagotani, S.; Zhang, X.M.; Ikeda, Y.; Matsuura, T.; Abe, K. Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain. J. Cereb. Blood Flow Metab. 2010, 30, 1487–1493, doi:10.1038/jcbfm.2010.32.
[150]
Yamashita, T.; Kawai, H.; Tian, F.F.; Ohta, Y.; Abe, K. Tumorigenic Development of Induced Pluripotent Stem Cells in Ischemic Mouse Brain. Cell Transplant. 2011, 20, 883–891, doi:10.3727/096368910X539092.
[151]
Oki, K.; Tatarishvili, J.; Wood, J.; Koch, P.; Wattananit, S.; Mine, Y.; Monni, E.; Tornero, D.; Ahlenius, H.; Ladewig, J.; et al. Human-Induced Pluripotent Stem Cells form Functional Neurons and Improve Recovery after Grafting in Stroke-Damaged Brain. Stem Cells 2012, 30, 1120–1133, doi:10.1002/stem.1104.
[152]
Oh, J.S.; Kim, K.N.; An, S.S.; Pennant, W.A.; Kim, H.J.; Gwak, S.J.; Yoon do, H.; Lim, M.H.; Choi, B.H.; Ha, Y. Cotransplantation of mouse neural stem cells (mNSCs) with adipose tissue-derived mesenchymal stem cells improves mNSC survival in a rat spinal cord injury model. Cell Transplant. 2011, 20, 837–849, doi:10.3727/096368910X539083.
[153]
Matsuda, R.; Yoshikawa, M.; Kimura, H.; Ouji, Y.; Nakase, H.; Nishimura, F.; Nonaka, J.; Toriumi, H.; Yamada, S.; Nishiofuku, M.; et al. Cotransplantation of mouse embryonic stem cells and bone marrow stromal cells following spinal cord injury suppresses tumor development. Cell Transplant. 2009, 18, 39–54, doi:10.3727/096368909788237122.
[154]
Nakagomi, N.; Nakagomi, T.; Kubo, S.; Nakano-Doi, A.; Saino, O.; Takata, M.; Yoshikawa, H.; Stern, D.M.; Matsuyama, T.; Taguchi, A. Endothelial cells support survival, proliferation, and neuronal differentiation of transplanted adult ischemia-induced neural stem/progenitor cells after cerebral infarction. Stem Cells 2009, 27, 2185–2195, doi:10.1002/stem.161.
[155]
Zhang, W.; Yan, Q.; Zeng, Y.S.; Zhang, X.B.; Xiong, Y.; Wang, J.M.; Chen, S.J.; Li, Y.; Bruce, I.C.; Wu, W. Implantation of adult bone marrow-derived mesenchymal stem cells transfected with the neurotrophin-3 gene and pretreated with retinoic acid in completely transected spinal cord. Brain Res. 2010, 1359, 256–271, doi:10.1016/j.brainres.2010.08.072.
[156]
Jin, K.; Mao, X.; Xie, L.; Galvan, V.; Lai, B.; Wang, Y.; Gorostiza, O.; Wang, X.; Greenberg, D.A. Transplantation of human neural precursor cells in Matrigel scaffolding improves outcome from focal cerebral ischemia after delayed postischemic treatment in rats. J. Cereb. Blood Flow Metab. 2010, 30, 534–544, doi:10.1038/jcbfm.2009.219.
[157]
Sanberg, P.R.; Eve, D.J.; Cruz, L.E.; Borlongan, C.V. Neurological disorders and the potential role for stem cells as a therapy. Br. Med. Bull. 2012, 101, 163–181.
[158]
Borlongan, C.V.; Chopp, M.; Steinberg, G.K.; Bliss, T.M.; Li, Y.; Lu, M.; Hess, D.C.; Kondziolka, D. Potential of stem/progenitor cells in treating stroke: the missing steps in translating cell therapy from laboratory to clinic. Regen. Med. 2008, 3, 249–250, doi:10.2217/17460751.3.3.249.
[159]
Borlongan, C.V. Cell therapy for stroke: remaining issues to address before embarking on clinical trials. Stroke 2009, 40, S146–S148, doi:10.1161/STROKEAHA.108.533091.
[160]
Chopp, M.; Steinberg, G.K.; Kondziolka, D.; Lu, M.; Bliss, T.M.; Li, Y.; Hess, D.C.; Borlongan, C.V. Who’s in favor of translational cell therapy for stroke: STEPS forward please? Cell Transplant. 2009, 18, 691–693, doi:10.3727/096368909X470883.
[161]
Borlongan, C.V.; Weiss, M.D. Baby STEPS: A giant leap for cell therapy in neonatal brain injury. Pediatr. Res. 2011, 70, 3–9, doi:10.1203/PDR.0b013e31821d0d00.