Stem cells and cell therapy: From basic sciences to clinical perspectives

Luciana Machado, Arnaldo Rodrigues Santos Jr.

Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil.
Centro Regional Universitário de Espírito Santo do Pinhal, Espírito Santo do Pinhal, SP, Brazil.

DOI: 10.4236/jbise.2013.66083                

Abstract

Stem cells are seen as a possible solution for organ and tissue regeneration and for the treatment or even cure of various diseases. There are basically two types of stem cells: embryonic and adult stem cells. Embryonic stem cells are derived from embryos and exhibit an extensive multiplication and differentiation potential. On the other hand, adult stem cells, which are found in bone marrow and other tissues, have a lower multiplication and differentiation capacity but are more easily isolated and applied. In adult stem cell therapies using bone marrow or umbilical cord blood transplantation, the differentiation of a certain cell type is induced and its multiplication is stimulated, followed by the implantation of these cells into damaged tissues. Examples of the application of stem cells include the treatment of autoimmune diseases such as type 1 diabetes mellitus and heart diseases. Stem cells open up new prospects for the treatment of a series of diseases. In this respect, basic knowledge of the mechanisms of growth and differentiation of these cells is of the utmost importance to optimize therapeutic results. In this review, we discuss the mechanisms of stem cell differentiation and describe the clinical results reported in the literature, mainly by Brazilian research groups.

Keywords

Stem Cells; Cell Differentiation; Cell Transplantation; Cell Therapy

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	[1] Mota, A.C.A., Soares, M.B.P. and Santos, R.R. (2005) Uso de terapia regenerativa com células-tronco da medula óssea em doenças cardiovasculares: perspectiva do hematologista. Revista Brasileira de Hematologia e Hemoterapia, 27, 126-132. doi:10.1590/S1516-84842005000200012
[2]	Soncini, M., Virtua, E., Gibelli, L., Zorzi, F., Denegri, M., Albertini, A., et al. (2007) Isolation and characterization of mesenchymal cells from human fetal membranes. Journal of Tissue Engineering and Regenerative Medicine, 1, 296-305. doi:10.1002/term.40
[3]	Santos Jr., A.R., Wada, M.L.F. and Carvalho, H.F. (2007) Diferenciação cellular. In: Carvalho, H.F., Recco-Pimentel, S.M., Eds., A Célula, 2nd Edition, Manole, São Paulo, 348-363.
[4]	Bajada, S., Mazakova, I., Richardson, J.B. and Ashammakhi, N. (2008) Updates on stem cells and their applications in regenerative medicine. Journal of Tissue Engineering and Regenerative Medicine, 2, 169-183. doi:10.1002/term.83
[5]	Bydlowski, S.P., Debes, A.A., Maselli, L.M.F. and Janz, F.L. (2009) Características biológicas das células-tronco mesenquimais. Revista Brasileira de Hematologia e Hemoterapia, 31, 25-35. doi:10.1590/S1516-84842009005000038
[6]	Zago, M.A. and Covas, D.T. (2007) Células-tronco: A nova fronteira da medicina. Atheneu, São Paulo.
[7]	Rodini, C.O., Suzuki, D.E., Nakahata, A.M., Pereira, M.C.L., Janjoppi, L., Toledo, S.R.C. and Okamoto, O.K. (2010) Aberrant signaling pathways in medulloblastomas: A stem cell connection. Arquivos de Neuro-psiquiatria, 68, 947-952. doi:10.1590/S0004-282X2010000600021
[8]	Gilbert, S.F. (2010) Developmental biology. 9th Edition, Sinauer Associates, Sunderlan.
[9]	Smith, A. (2001) Embryonic stem cells. In: Marshak, D.R., Gardner, R.L. and Gottlieb, D., Eds., Stem Cell Biology, Cold Spring Harbor, New York, 205-230.
[10]	Lodish, H., Berk, A., Matsudaira, P., Kaiser, C.A., Krieger, M., Scott, M.P., et al. (2005) Molecular cell biology. 5th Edition, W.H. Freeman and Co., New York.
[11]	Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. and Walter, P. (2008) Molecular biology of the cell. 5th Edition, Garland Science, New York.
[12]	Pittenger, M.F. and Marshak, D.R. (2001) Mesenchymal stem cells of human adult bone marrow. In: Marshak, D.R., Gardner, R.L. and Gottlieb, D., Eds., Stem Cell Biology, Cold Spring Harbor, New York, 349-373.
[13]	Araujo, J.D., Araujo Filho, J.D., Ciorlin, E., Ruiz, M.A., Ruiz, L.P., Greco, O.T., et al. (2005) Terapia celular no tratamento da isquemia crítica dos membros inferiores. Jornal Vascular Brasileiro, 4, 357-365. doi:10.1590/S1677-54492005000400011
[14]	Williams, J.T., Southerland, S.S., Lucas, P.A., Souza, J.W., Calcutt, A.F. and Cartledge, R.G. (1999) Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes. American Surgeon, 65, 22-26.
[15]	Panicker, M.M. and Rao, M. (2001) Stem cells and neurogenesis. In: Marshak, D.R., Gardner, R.L. and Gottlieb, D., Eds., Stem Cell Biology, Cold Spring Harbor, New York, 399-438.
[16]	Junqueira, L.C. and Carneiro, J. (2008) Histologia básica, 11th Edition, Guanabara Koogan, Rio de Janeiro.
[17]	Mazzetti, M.P.V., Oliveira, I.S., Miranda-Ferreira, R., Fauaz, G., Ribeiro, C.N., Gomes, P.O., Pontes, P., Ferreira, A.T. and Eça, L.P. (2010) Qualitative and quantitative analysis of rabbit’s fat mesenchymal stem cells. Acta Cirúrgica Brasileira, 25, 24-27. doi:10.1590/S0102-86502010000100007
[18]	Mizuno, H. and Hyakusoku, H. (2003) Mesogenic potential and future clinical perspective of human processed lipoaspirate cells. Journal of Nippon Medical School, 70, 300-306. doi:10.1272/jnms.70.300
[19]	Santos Jr., A.R. and Wada, M.L.F. (2007) Polímeros biorreabsorvíveis como arcabouços para cultura de células e engenharia tecidual. Polímeros Ciência e Tecnologia, 17, 308-317. doi:10.1590/S0104-14282007000400010
[20]	Silva, T.S.N., Primo, B.T., Silva Jr., A.N., Machado, D.C., Viezzer, C. and Santos, L.A. (2011) Use of calcium phosphate cement scaffolds for bone tissue engineering: In Vitro Study. Acta Cirúrgica Brasileira, 26, 7-11. doi:10.1590/S0102-86502011000100003
[21]	Gomes, R.S. (2011) Perspectivas do uso de células-tronco em cirurgia plástica. Revista Brasileira de Cirurgia Plástica, 26, 151-159. doi:10.1590/S1983-51752011000100027
[22]	Reis, P.E.O. (2005) Bone marrow stem cells and their role in angiogenesis. Jornal Vascular Brasileiro, 4, 366370. doi:10.1590/S1677-54492005000400012
[23]	Iba, O., Matsubara, H., Nozawa, Y., Fujiyama, S., Amano, K., Mori, Y., et al. (2002) Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs. Circulation, 106, 2019-2025. doi:10.1161/01.CIR.0000031332.45480.79
[24]	Tateishi-Yuyama, E.T., Matsubara, H., Murohara, T., Ikeda, U., Shintani, S., Masaki, H., et al. (2002) Therapeutic angio-genesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: A pilot study and a randomized controlled trial. Lancet, 360, 427435. doi:10.1016/S0140-6736(02)09670-8
[25]	Eça, L.P., Ramalho, R.B., Oliveira, I.S., Gomes, P.O., Pontes, P., Ferreira, A.T. and Mazzetti, M.P.V. (2009) Comparative study of technique to obtain stem cells from bone marrow collection between the iliac crest and the femoral epiphysis in rabbits. Acta Cirúrgica Brasileira, 24, 400-404. doi:10.1590/S0102-86502009000500011
[26]	Feitosa, M.L.T., Fadel, L., Beltrão-Braga, P.C.B., Wenceslau, C.V., Kerkis, I., Kerkis, A., Birgel Jr., E.H.B., Martins, J.F.P., Maritns, D.S., Miglino, M.A. and Ambrósio, C.E. (2010) Successful transplant of mesenchymal stem cells in induced osteonecrosis of the ovine femoral head. Pre-liminary results. Acta Cirúrgica Brasileira, 25, 416-422. doi:10.1590/S0102-86502010000500006
[27]	Orlic, D., Kajstura, J., Stefano, C., Jakoniuk, I., Anderson, S.M., Li, B., et al. (2001) Bone marrow cells regenerate infarcted myocardium. Nature, 410, 701-705. doi:10.1038/35070587
[28]	Santos, R.R., Soares, M.B.P. and Carvalho, A.C.C. (2004) Transplante de células da medula óssea no tratamento da cardiopatia chagásica crônica. Revista da Sociedade Brasileira de Medicina Tropical, 37, 490-495. doi:10.1590/S0037-86822004000600012
[29]	Vilas-Boas, F., Feitos, G.S., Soares, M.B.P., Mota, A., Pinho-Filho, J.A., Almeida, A.J.G., Andrade, M.V., Carvalho, H.G., Dourado-Oliveira, A. and Ribeiro-dos-Santos, R. (2006) Resultados iniciais do transplante de células de medula óssea para o miocárdio de pacientes com insuficiência cardíaca de etiologia chagásica. Arquivos Brasileiros de Cardiologia, 87, 159-166. doi:10.1590/S0066-782X2006001500014
[30]	Vilas-Boas, F., Feitosa, G.S., Soares, M.B.P., Pinho-Filho, J.A., Mota, A.C.A., Almeida, A.J.G., Andrade, M.V., Carvalho, H.G., Oliveira, A.D. and Ribeiro-dos-Santos, R. (2011) Transplante de células da medula óssea na insuficiência cardíaca chagásica: Relato da primeira experiência humana. Arquivos Brasileiro de Cardiologia, 96, 325-331. doi:10.1590/S0066-782X2011005000028
[31]	Dallan, L.A.O., Gowdak, L.H., Lisboa, L.A.F., Schettert, J.E., Krieger, J.E., Cesar, L.A.M., Oliveira, S.A. and Stolf, N.A.G. (2008) Terapia celular associada à revascularização transmiocárdica laser como proposta no tratamento da angina refratária. Revista Brasileira de Cirurgia Cardiovascular, 23, 46-52. doi:10.1590/S0102-76382008000100009
[32]	Kalil, R.A.K., Ott, D., Sant'Anna, R., Dias, E., MarquesPereira, J.P., Delgado-Cañedo, A., Nardi, N.B., Sant’Anna, J.R.M., Prates, P.R. and Nesralla, I. (2008) Autologous transplantation of bone marrow mononuclear stem cells by mini-thoracotomy in dilated cardiomyopathy: Technique and early results. Sao Paulo Medical Journal, 126, 75-81. doi:10.1590/S1516-31802008000200003
[33]	Greco, O.T., Greco, R.L., Abreu, A.C., Jacob, J.L.B., Ardito, R.V., Takeda, R.T., Parro Jr., A., Sallis, F.V., Lago, M.R. and Ruiz, M.A. (2009) Ressincronização cardíaca e terapia celular: Existe terapia associativa? Revista Brasileira de Hematologia e Hemoterapia, 31, 93-98. doi:10.1590/S1516-84842009005000025
[34]	Fortier, L.A. (2005) Stem cells: Classifications, controversies, and clinical applications. Veterinary Surgery, 34, 415-423. doi:10.1111/j.1532-950X.2005.00063.x
[35]	Gronthos, S., Mankani, M., Brahim, J., Robey, P.G. and Shi, S. (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proceedings of National Academic of Science of USA, 97, 13625-13630. doi:10.1073/pnas.240309797
[36]	Miura, M., Gronthos, S., Zhao, M., Lu, B., Fisher, L.W., Robey, P.G., et al. (2003) SHED: Stem cells from human exfoliated deciduous teeth. Proceedings of National Academic of Science of USA, 100, 5807-5812. doi:10.1073/pnas.0937635100
[37]	Gronthos, S., Brahim, J., Li, W., Fisher, L.W., Cherman, N., Boyde, A., et al. (2002) Stem cell properties of human dental pulp stem cells. Journal of Dental Research, 81, 531-535. doi:10.1177/154405910208100806
[38]	Liu, J., Jin, T., Ritchie, H.H., Smith, A.J. and Clarkson, B.H. (2005) In Vitro differentiation and mineralization of human dental pulp cells induced by dentin extract. In Vitro Cellular and Developmental Biology Animal, 41, 232238. doi:10.1290/0502014.1
[39]	Soares, A.P., Knop, L.A.H., Jesus, A.A. and Araújo, T.M. (2007) Células-tronco em odontologia. Revista Dental Press de Ortodontologia e Ortopedia Facial, 12, 33-40. doi:10.1590/S1415-54192007000100006
[40]	Lovschall, H., Tummers, M., Thesleff, I., Fuchtbauer, E.M. and Poulsen, K. (2005) Activation of the Notch signaling pathway in response to pulp capping of rat molars. European Journal of Oral Science, 113, 312-317. doi:10.1111/j.1600-0722.2005.00221.x
[41]	Demarco, F.F., Conde, M.C.M., Cavalcanti, B.N., Casagrande, L., Sakai, V.T. and Nör, J.E. (2011) Dental pulp tissue engineering. Brazilian Dental Journal, 22, 3-13.
[42]	Voltarelli, J.C., Stracieri, A.B.P.L., Oliveira, M.C.B., Godoi, D.F., Moraes, D.A., Pieroni, F., Malmegrim, K.C.R., Coutinho, M.A., Simões, B.P., Massumoto, C., Hamerschlak, N., Scheinberg, M., Ferreira, E., Coutinho, M., Ostronoff, M., Sturaro, D. and Dulley, F. (2005) Transplante de células-tronco hematopoéticas em doenças reumáticas parte 2: Experiência brasileira e perspectivas futuras. Revista Brasileira de Reumatologia, 45, 301-312. doi:10.1590/S0482-50042005000500004
[43]	Voltarelli, J.C., Stracieri, A.B.P.L., Oliveira, M.C.B., Godoi, D.F., Moraes, D.A., Pieroni, F., Malmegrim, K.C.R., Coutinho, M.A. and Simões, B.P. (2005) Transplante de células-tronco hematopoéticas em doenças reumáticas parte 1: Experiência internacional. Revista Brasileira de Reumatologia, 45, 229-241. doi:10.1590/S0482-50042005000400007
[44]	Pereira, L.V. (2008) A importancia do uso das células tronco para a saúde pública. Ciência & Saúde Coletiva, 13, 7-14. doi:10.1590/S1413-81232008000100002
[45]	Rosa, S.B., Voltarelli, J.C., Chies, J.A.B. and Pranke, P. (2007) Use of stem cells in autoimmune diseases. Brazilian Journal of Medical and Biological Research, 40, 1579-1597. doi:10.1590/S0100-879X2006005000165