JBiSE  Vol.7 No.2 , February 2014
Stem cells therapy for regenerative medicine: Principles of present and future practice
ABSTRACT
The characterization and isolation of various stem cell populations, from embryonic to tissue-derived stem cells and induced pluripotent stem cells (iPSCs), have led to a rapid growth in the field of stem cell research and its potentially clinical application in the field of regenerative medicine and tissue repair. Stem cell therapy has recently progressed from the preclinical to the early clinical trial arena for a variety of diseases states, although further knowledge on action mechanisms, long-term safety issues, and standardization and characterization of the therapeutic cell products remains to be thoroughly elucidated. In this paper we summarize the current state of the art of basic and clinical research that were highlighted at the 2012 meeting of the Spanish Cell Therapy Network. This includes the current research involving in genomic and transcriptomic characterization of selected stem cell populations, studies of the role of resident and transplanted stem cells during tissue regeneration and their mechanism of action, improved new strategies of tissue engineering, transplantation of mesenchymal stem cells (MSCs) in different animal models of disease, disease correction by iPSCs, and preliminary results of cell therapy in human clinical trials.

Cite this paper
Andrades, J. , Becerra, J. , Muñoz-Chápuli, R. , Martínez, S. , Raya, Á. , García-Sancho, J. and Moraleda, J. (2014) Stem cells therapy for regenerative medicine: Principles of present and future practice. Journal of Biomedical Science and Engineering, 7, 49-57. doi: 10.4236/jbise.2014.72008.
References
[1]   Sipp, D. (2011) Global challenges in stem cell research and the many roads ahead. Neuron, 70, 573-576.
http://dx.doi.org/10.1016/j.neuron.2011.05.008

[2]   Trounson, A. and Dewitt, N.D. (2012) Stem cell biology: Towards the reality of cell therapeutics. Nature Cell Biology, 14, 331. http://dx.doi.org/10.1038/ncb2469

[3]   Mustafiz, T., Portelius, E., Gustavsson, M.K., et al. (2010) Characterization of the brain beta-amyloid isoform pattern at different ages of Tg2576 mice. Neurodegenerative Diseases, 8, 352-363.
http://dx.doi.org/10.1159/000323871

[4]   Kordower, J.H. (2008) Introduction to the special ASNTR issue. Cell Transplantation, 17, 361-362.

[5]   Cicchetti, F., Drouin-Ouellet, J. and Gross, R.E. (2009) Environmental toxins and Parkinson’s disease: What have we learned from pesticide-induced animal models? Trends of Pharmacology Science, 30, 475-483.
http://dx.doi.org/10.1016/j.tips.2009.06.005

[6]   Ekdahl, C.T., Kokaia, Z. and Lindvall, O. (2009) Brain inflammation and adult neurogenesis: The dual role of microglia. Neuroscience, 158, 1021-1029.
http://dx.doi.org/10.1016/j.neuroscience.2008.06.052

[7]   Arvidsson, L., Fagerlund, M., Jaff, N., et al. (2011) Distribution and characterization of progenitor cells within the human filum terminale. PloS One, 6, e27393.
http://dx.doi.org/10.1371/journal.pone.0027393

[8]   Ekdahl, C.T. (2012) Microglial activation-tuning and pruning adult neurogenesis. Frontier of Pharmacology, 3, 41.
http://dx.doi.org/10.3389/fphar.2012.00041

[9]   Winner, B., Kohl, Z. and Gage, F.H. (2011) Neurodegenerative disease and adult neurogenesis. European Journal of Neuroscience, 33, 1139-1151.
http://dx.doi.org/10.1111/j.1460-9568.2011.07613.x

[10]   Blanquer, M., Pérez-Espejo, M.A., Martínez-Lage, J.F., et al. (2010) A surgical technique of spinal cord cell transplantation in amyotrophic lateral sclerosis. Journal of Neuroscience Methods, 191, 255-257.
http://dx.doi.org/10.1016/j.jneumeth.2010.06.014

[11]   Blanquer, M., Moraleda, J.M., Iniesta, F., et al. (2012) Neurotrophic bone marrow celular nests prevent spinal motoneuron degeneration in amyotrophic lateral sclerosis patients: A pilot safety study. Stem Cells, 30, 1277-1285.
http://dx.doi.org/10.1002/stem.1080

[12]   Araque-Monrós, M.C., Gil-Santos, L., Monleón-Pradas, M. and Más-Estellés, J. (In press) New concept for a regenerative and resorbable prosthesis for tendon and ligament. Physicochemical and biological characterization of PLA braided biomaterial. Journal of Biomedical Materials Research: Part A.

[13]   Andrades, J.A., Motaung, S.C., Jiménez-Palomo, P., et al. (2012) Induction of superficial zone protein (SZP)/lubricin/PRG 4 in muscle-derived mesenchymal stem/progenitor cells by transforming growth factor-beta1 and bone morphogenetic protein-7. Arthritis Research and Therapy, 14, 31-42. http://dx.doi.org/10.1186/ar3793

[14]   Granero-Moltó, F., Weis, J.A., Miga, M.I., et al. (2009) Regenerative effects of transplanted mesenchymal stem cells in fracture healing. Stem Cells, 27, 1887-1898.
http://dx.doi.org/10.1002/stem.103

[15]   Evans, C.H. (2013) Advances in regenerative orthopedics. Mayo Clinic Proceedings, 88, 1323-1339.
http://dx.doi.org/10.1016/j.mayocp.2013.04.027

[16]   Orozco, L., Soler, R., Morera, C., et al. (2011) Intervertebral disc repair by autologous mesenchymal bone marrow cells: A pilot study. Transplantation, 92, 822-828.
http://dx.doi.org/10.1097/TP.0b013e3182298a15

[17]   Gallego, L., Junquera, L., García, E., et al. (2010) Repair of rat mandibular bone defects by alveolar osteoblasts in a novel plasma-derived albumin scaffold. Tissue Engineering Part A, 16, 1179-1187.
http://dx.doi.org/10.1089/ten.tea.2009.0517

[18]   Le Blanc, K. and Ringden, O. (2007) Immunomodulation by mesenchymal stem cells and clinical experience. Journal of International Medicine, 262, 509-525.
http://dx.doi.org/10.1111/j.1365-2796.2007.01844.x

[19]   Chang, C.H., Kuo, T.F., Lin, F.H., et al. (2011) Tissue engineering-based cartilage repair with mesenchymal stem cells in a porcine model. Journal of Orthopaedic Research, 29, 1874-1880.
http://dx.doi.org/10.1002/jor.21461

[20]   Bernardo, M.E., Pagliara, D. and Locatelli, F. (2011) Mesenchymal stromal cell therapy: A revolution in Regenerative Medicine? Bone Marrow Transplantation, 47, 164-171. http://dx.doi.org/10.1038/bmt.2011.81

[21]   Takahashi, K. and Yamanaka, S. (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663-676.
http://dx.doi.org/10.1016/j.cell.2006.07.024

[22]   Vogel, G. (2010) Stem cells. Reprogrammed cells come up short, for now. Science, 327, 1191-1197.

[23]   Graf, T. and Enver, T. (2009) Forcing cells to change lineages. Nature, 462, 587-594.
http://dx.doi.org/10.1038/nature08533

[24]   Vierbuchen, T. and Wernig, M. (2011) Direct lineage conversions: Unnatural but useful? Nature Biotechnology, 29, 892-907. http://dx.doi.org/10.1038/nbt.1946

[25]   Mizrak, S.C., Chikhovskaya, J.V., Sadri-Ardekani, H., et al. (2009) Embryonic stem cell-like cells derived from adult human testis. Human Reproduction, 25, 158-167.
http://dx.doi.org/10.1093/humrep/dep354

[26]   Aasen, T., Raya, A., Barrero, M.J., et al. (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nature Biotechnology, 26, 1276-1284. http://dx.doi.org/10.1038/nbt.1503

[27]   Giorgetti, A., Montserrat, N., Aasen, T., et al. (2009) Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2. Cell Stem Cell, 5, 353-357. http://dx.doi.org/10.1016/j.stem.2009.09.008

[28]   Ebert, A.D., Yu, J., Rose, F.F., et al. (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature, 457, 277-280.
http://dx.doi.org/10.1038/nature07677

[29]   Lee, H., Park, J., Forget, B.G. and Gaines, P. (2009) Induced pluripotent stem cells in regenerative medicine: An argument for continued research on human embryonic stem cells. Regenerative Medicine, 4, 759-769.
http://dx.doi.org/10.2217/rme.09.46

[30]   Carvajal-Vergara, X., Sevilla, A., D’Souzza, S.L., et al. (2010) Patient-specific induced pluripotent stem-cell derived models of LEOPARD syndrome. Nature, 465, 808-812. http://dx.doi.org/10.1038/nature09005

[31]   Ku, S., Soragni, E., Campau, E., Thomas, E.A., Altun, G., Laurent, L.C., Loring, J.F., Napierala, M. and Gottesfeld, J.M. (2010) Friedreich’s ataxia induced pluripotent stem cells model intergenerational GAA-TTC triplet repeat instability. Cell Stem Cell, 7, 631-637.
http://dx.doi.org/10.1016/j.stem.2010.09.014

[32]   Moretti, A., Bellin, M., Welling, A., et al. (2010) Patient-specific induced pluripotent stem-cell models for long-QT syndrome. New England Journal of Medicine, 363, 1397-1409.
http://dx.doi.org/10.1056/NEJMoa0908679

[33]   Rashid, S.T., Corbineau, S., Hannan, N., Marciniak, S.J., Miranda, E., Alexander, G., Huang-Doran, I., Griffin, J., Ahrlund-Richter, L., Skepper, J., Semple, R., Weber, A., Lomas, D.A. and Vallier, L. (2010) Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. Journal of Clinical Investigation, 120, 3127-3136.
http://dx.doi.org/10.1172/JCI43122

[34]   Zhang, S., Chen, S., Li, W., Guo, X.P., Zhao, P., Xu, J.Y., Chen, Y., Pan, Q., Liu, X.R., Zychlinski, D., Lu, H., Tortorella, M.D., Schambach, A., Wang, Y., Pei, D.Q. and Esteban, M.A. (2011) Rescue of ATP7B function in hepatocyte-like cells from Wilson’s disease induced pluri-potent stem cells using gene therapy or the chaperone drug curcumin. Human Molecular Genetics, 20, 3176-3187. http://dx.doi.org/10.1093/hmg/ddr223

[35]   Brennand, K.J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., Li, Y., Mu, Y.L., Chen, G., Yu, D., McCarthy, S., Sebat, J. and Gage, F.H. (2011) Modelling schizophrenia using human induced pluripotent stem cells. Nature, 473, 221-225.
http://dx.doi.org/10.1038/nature09915

[36]   Sánchez-Danés, A., Richaud-Patin, Y., Carballo-Carbajal, I., Jiménez-Delgado, S., Caig, C., Mora, S., Di Guglielmo, C., Ezquerra, M., Patel, B., Giralt, A., Canals, J.M., Memo, M., Alberch, J., López-Barneo, J., Vila, M., Cuervo, A.M., Tolosa, E., Consiglio, A. and Raya, A. (2012) Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson’s disease. EMBO Molecular Medicine, 4, 380-395.
http://dx.doi.org/10.1002/emmm.201200215

[37]   Raya, A., Rodríguez-Pizá, I., Guenechea, G., Vassena, R., Navarro, S., Barrero, M.J., Consiglio, A., Castellà, M., Río, P., Sleep, E., González, F., Tiscornia, G., Garreta, E., Aasen, T., Veiga, A., Verma, I.M., Surrallés, J., Bueren, J. and Belmonte, J.C.I. (2009) Disease-corrected haematopoietic progenitors from Falconi anaemia induced pluri-potent stem cells. Nature, 460, 53-59.
http://dx.doi.org/10.1038/nature08129

[38]   Ma, N., Liao, B., Zhang, H., et al. (2013) TALEN-mediated gene correction in integration-free-beta-thalassemia iPSCs. Journal of Biology and Chemistry, Epub ahead of print.

[39]   Perez-Pinera, P., Ousterout, D.G. and Gersbach, C.A. (2012) Advances in targeted genome editing. Current Opinion in Chemical Biology, 16, 268-277.
http://dx.doi.org/10.1016/j.cbpa.2012.06.007

[40]   Okano, H., Nakamura, M., Yoshida, K., Okada, Y., Tsuji, O., Nori, S., Ikeda, E., Yamanaka, S. and Miura, K. (2013) Steps toward safe cell therapy using induced pluripotent stem cells. Circulation Research, 112, 523-533.
http://dx.doi.org/10.1161/CIRCRESAHA.111.256149

[41]   Ronen, D. and Benvenisty, N. (2012) Genomic stability in reprogramming. Current Opinion in Genetics & Development, 22, 444-449.
http://dx.doi.org/10.1016/j.gde.2012.09.003

[42]   Cyranoski, D. (2013) Stem cells cruise to clinic. Nature, 494, 413. http://dx.doi.org/10.1038/494413a

[43]   Cyranoski, D. (2012) Stem-cell pioneer banks on future therapies. Nature, 488, 139.
http://dx.doi.org/10.1038/488139a

 
 
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