Adult Stem Cells
Andreas Nussler
Eberhard Karls Universität Tübingen, Department of Traumatology, Tübingen, Germany
Search for more papers by this authorSahar Olsadat Sajadian
Eberhard Karls Universität Tübingen, Department of Traumatology, Tübingen, Germany
Search for more papers by this authorAndreas Nussler
Eberhard Karls Universität Tübingen, Department of Traumatology, Tübingen, Germany
Search for more papers by this authorSahar Olsadat Sajadian
Eberhard Karls Universität Tübingen, Department of Traumatology, Tübingen, Germany
Search for more papers by this authorHossein Baharvand
Search for more papers by this authorNasser Aghdami
Search for more papers by this authorSummary
Adult stem cells are found in juvenile and adult organisms. Their characteristics are self-renewal, including proliferation, multipotency, and maintenance of their differentiation potential to repair damaged tissue after cell division. Since adult stem cells raise little ethical concerns and are easy to harvest, many in vitro assays and clinical applications have been established in recent decades. Although adult stem cells seem to be an alternative to embryonic stem cells and tailored stem cells, which generate more ethical and safety concerns, several questions still have to be answered before they can be used at a larger scale. In this chapter, we summarize the current knowledge, applications, and pitfalls regarding the use of adult stem cells.
References
- Thomas ED, HL Lochte Jr, WC Lu and JW Ferrebee (1957). Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. New England Journal of Medicine 257: 491–496.
- Bianco P and PG Robey (2000). Marrow stromal stem cells. Journal of Clinical Investigation 105: 1663–1668.
- Sanchez-Ramos JR (2002). Neural cells derived from adult bone marrow and umbilical cord blood. Journal of neuroscience research 69: 880–893.
- Becker AJ, EA McCulloch and JE Till (1963). Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197, 452–454
- Orkin SH (2000). Diversification of haematopoietic stem cells to specific lineages. Nature Reviews Genetics 1: 57–64.
- Owen M (1988). Marrow stromal stem cells. Journal of Cell Science. Supplement 10: 63.
- Friedenstein AJ, KV Petrakova, AI Kurolesova and GP Frolova (1968). Heterotopic transplants of bone marrow. Transplantation 6: 230–247.
- Alison M and S Islam (2009). Attributes of adult stem cells. The Journal of Pathology 217: 144–160.
- Caplan AI (1991). Mesenchymal stem cells. Journal of Orthopaedic Research 9: 641–650.
- Horwitz EM, PL Gordon, WK Koo, JC Marx, MD Neel, RY McNall, L Muul and T Hofmann (2002). Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proceedings of the National Academy of Sciences 99: 8932–8937.
- Keating A, L Berkahn and R Filshie (1998). A Phase I study of the transplantation of genetically marked autologous bone marrow stromal cells: University of Toronto, Ontario, Canada. Human Gene Therapy 9: 591–600.
- Horwitz E, K Le Blanc, M Dominici, I Mueller, I Slaper-Cortenbach, F Marini, R Deans, D Krause and A Keating (2005). Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy 7: 393–395.
- Pittenger MF, AM Mackay, SC Beck, RK Jaiswal, R Douglas, JD Mosca, MA Moorman, DW Simonetti, S Craig and DR Marshak (1999). Multilineage potential of adult human mesenchymal stem cells. Science 284: 143–147.
- Caplan AI and SP Bruder (2001). Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends in Molecular Medicine 7: 259–264.
- Brinchmann JE (2008). Expanding autologous multipotent mesenchymal bone marrow stromal cells. Journal of the Neurological Sciences 265: 127–130.
- Wei G, G Schubiger, F Harder and AM Müller (2000). Stem cell plasticity in mammals and transdetermination in Drosophila: common themes? Stem Cells 18: 409–414.
- Phinney DG and DJ Prockop (2007). Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair – current views. Stem Cells 25: 2896–2902.
- Kahn A and D Simmons (1977). Chondrocyte-to-osteocyte transformation in grafts of perichondrium-free epiphyseal cartilage. Clinical Orthopaedics and Related Research 129: 299–304.
- Hattori H, M Sato, K Masuoka, M Ishihara, T Kikuchi, T Matsui, B Takase, T Ishizuka, M Kikuchi and K Fujikawa (2004). Osteogenic potential of human adipose tissue-derived stromal cells as an alternative stem cell source. Cells Tissues Organs 178: 2–12.
- Wagers AJ and IL Weissman (2004). Plasticity of adult stem cells. Cell 116: 639–648.
- Wagers AJ, RI Sherwood, JL Christensen and IL Weissman (2002). Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297: 2256–2259.
- Anderson DJ, FH Gage and IL Weissman (2001). Can stem cells cross lineage boundaries? Nature Medicine 7: 393–395.
- Lagasse E, H Connors, M Al-Dhalimy, M Reitsma, M Dohse, L Osborne, X Wang, M Finegold, IL Weissman and M Grompe (2000). Purified hematopoietic stem cells can differentiate into hepatocytes in vivo . Nature Medicine 6: 1229–1234.
- Seeliger C, M Culmes, L Schyschka, X Yan, G Damm, Z Wang, J Kleeff, W Thasler, J Hengstler and U Stockle (2013). Decrease of global methylation improves significantly hepatic Differentiation of Ad-MSCs: Possible future application for urea detoxification. Cell Transplantation 22: 119–131.
- Hong SH, EJ Gang, JA Jeong, C Ahn, SH Hwang, IH Yang, HK Park, H Han and H Kim (2005). In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells. Biochemical and Biophysical Research Communications 330: 1153–1161.
- Salem HK and C Thiemermann (2010). Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 28: 585–596.
- Arnhold S, P Heiduschka, H Klein, Y Absenger, S Basnaoglu, F Kreppel, S Henke-Fahle, S Kochanek, K-U Bartz-Schmidt and K Addicks (2006). Adenovirally transduced bone marrow stromal cells differentiate into pigment epithelial cells and induce rescue effects in RCS rats. Investigative Ophthalmology and Visual Science 47: 4121–4129.
- Arnhold S, Y Absenger, H Klein, K Addicks and U Schraermeyer (2007). Transplantation of bone marrow-derived mesenchymal stem cells rescue photoreceptor cells in the dystrophic retina of the rhodopsin knockout mouse. Graefe's Archive for Clinical and Experimental Ophthalmology 245: 414–422.
- Fu X, L Fang, X Li, B Cheng and Z Sheng (2006). Enhanced wound-healing quality with bone marrow mesenchymal stem cells autografting after skin injury. Wound Repair and Regeneration 14: 325–335.
- Nakagawa H, S Akita, M Fukui, T Fujii and K Akino (2005). Human mesenchymal stem cells successfully improve skin-substitute wound healing. British Journal of Dermatology 153: 29–36.
- Herrera MB, B Bussolati, S Bruno, V Fonsato, GM Romanazzi and G Camussi (2004). Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. International Journal of Molecular Medicine 14: 1035.
- Ferrari G, D Angelis, M Coletta, E Paolucci, A Stornaiuolo, G Cossu and F Mavilio (1998). Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279: 1528–1530.
- Gritti A, AL Vescovi and R Galli (2002). Adult neural stem cells: plasticity and developmental potential. Journal of Physiology – Paris 96: 81–90.
- Orlic D, J Kajstura, S Chimenti, I Jakoniuk, SM Anderson, B Li, J Pickel, R McKay, B Nadal-Ginard and DM Bodine (2001). Bone marrow cells regenerate infarcted myocardium. Nature 410: 701–705.
- Murrell W, F Féron, A Wetzig, N Cameron, K Splatt, B Bellette, J Bianco, C Perry, G Lee and A Mackay-Sim (2005). Multipotent stem cells from adult olfactory mucosa. Developmental Dynamics 233: 496–515.
- Short B, N Brouard, T Occhiodoro-Scott, A Ramakrishnan and PJ Simmons (2003). Mesenchymal stem cells. Archives of Medical Research 34: 565–571.
- Khoo CP, P Pozzilli and MR Alison (2008). Endothelial progenitor cells and their potential therapeutic applications. Regenerative Medicine 3: 863–876.
- Im G-I, Y-W Shin and K-B Lee (2005). Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthritis and Cartilage 13: 845–853.
- Banas A, T Teratani, Y Yamamoto, M Tokuhara, F Takeshita, G Quinn, H Okochi and T Ochiya (2007). Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology 46: 219–228.
- Wu X-B and R Tao (2012). Hepatocyte differentiation of mesenchymal stem cells. Hepatobiliary and Pancreatic Diseases International 11: 360–371.
- Aurich H, M Sgodda, P Kaltwaßer, M Vetter, A Weise, T Liehr, M Brulport, JG Hengstler, MM Dollinger and WE Fleig (2009). Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo . Gut 58: 570–581.
- Shigemura N, M Okumura, S Mizuno, Y Imanishi, T Nakamura and Y Sawa (2006). Autologous transplantation of adipose tissue-derived stromal cells ameliorates pulmonary emphysema. American Journal of Transplantation 6: 2592–2600.
- Seaberg RM and D van der Kooy (2002). Adult rodent neurogenic regions: the ventricular subependyma contains neural stem cells, but the dentate gyrus contains restricted progenitors. The Journal of Neuroscience 22: 1784–1793.
- Alvarez-Buylla A, B Seri and F Doetsch (2002). Identification of neural stem cells in the adult vertebrate brain. Brain Research Bulletin 57: 751–758.
- Laywell ED, P Rakic, VG Kukekov, EC Holland and DA Steindler (2000). Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proceedings of the National Academy of Sciences 97: 13883–13888.
- Teng YD, EB Lavik, X Qu, KI Park, J Ourednik, D Zurakowski, R Langer and EY Snyder (2002). Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proceedings of the National Academy of Sciences 99: 3024–3029.
- Iwanami A, S Kaneko, M Nakamura, Y Kanemura, H Mori, S Kobayashi, M Yamasaki, S Momoshima, H Ishii and K Ando (2005). Transplantation of human neural stem cells for spinal cord injury in primates. Journal of Neuroscience Research 80: 182–190.
- Kruger GM, JT Mosher, S Bixby, N Joseph, T Iwashita and SJ Morrison (2002). Neural crest stem cells persist in the adult gut but undergo changes in self-renewal, neuronal subtype potential, and factor responsiveness. Neuron 35: 657–669.
- Till JE and EA McCulloch (1961). A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiation Research 14: 213–222.
- Theise ND, S Badve, R Saxena, O Henegariu, S Sell, JM Crawford and DS Krause (2000). Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology 31: 235–240.
- Krause DS, ND Theise, MI Collector, O Henegariu, S Hwang, R Gardner, S Neutzel and SJ Sharkis (2001). Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105: 369–377.
- Wu Y, RC Zhao and EE Tredget (2010). Concise Review: Bone marrow-derived stem/progenitor cells in cutaneous repair and regeneration. Stem Cells 28: 905–915.
- Morrison SJ and IL Weissman (1994). The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity 1: 661–673.
- Baum CM, IL Weissman, AS Tsukamoto, A-M Buckle and B Peault (1992). Isolation of a candidate human hematopoietic stem-cell population. Proceedings of the National Academy of Sciences 89: 2804–2808.
- Spangrude GJ, S Heimfeld and IL Weissman (1988). Purification and characterization of mouse hematopoietic stem cells. Science 241: 58–62.
- Perkins AC (1998). Enrichment of blood from embryonic stem cells in vitro . Reproduction, Fertility and Development 10: 563–572.
- Gunsilius E, G Gastl and A Petzer (2001). Hematopoietic stem cells. Biomedicine and pharmacotherapy 55: 186–194.
- Weissman I (2000). Stem cells: units of development, units of regeneration, and units in evolution. Cell 100: 157–168.
-
Cohnheim J (1867). Ueber entzündung und eiterung. Virchows Archiv 40: 1–79.
10.1007/BF02968135 Google Scholar
- Prockop DJ (1997). Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276: 71–74.
- Friedenstein AJ, J Gorskaja and N Kulagina (1976). Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Experimental Hematology 4: 267–274.
- Lindroos B, R Suuronen and S Miettinen (2011). The potential of adipose stem cells in regenerative medicine. Stem Cell Reviews and Reports 7: 269–291.
- Fraser JK, I Wulur, Z Alfonso and MH Hedrick (2006). Fat tissue: an underappreciated source of stem cells for biotechnology. Trends in Biotechnology 24: 150–154.
- Boquest AC, A Shahdadfar, JE Brinchmann and P Collas (2006). Isolation of stromal stem cells from human adipose tissue. In Nuclear Reprogramming: Methods and Protocols, S. Pells (ed.). Springer: Berlin; 35–46.
- McIntosh K, S Zvonic, S Garrett, JB Mitchell, ZE Floyd, L Hammill, A Kloster, Y Di Halvorsen, JP Ting and RW Storms (2006). The immunogenicity of human adipose-derived cells: temporal changes in vitro . Stem Cells 24: 1246–1253.
- Kucerova L, V Altanerova, M Matuskova, S Tyciakova and C Altaner (2007). Adipose tissue–derived human mesenchymal stem cells mediated prodrug cancer gene therapy. Cancer Research 67: 6304–6313.
- Zhu W, W Xu, R Jiang, H Qian, M Chen, J Hu, W Cao, C Han and Y Chen (2006). Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo . Experimental and Molecular Pathology 80: 267–274.
- Cousin B, E Ravet, S Poglio, F De Toni, M Bertuzzi, H Lulka, I Touil, M André, J-L Grolleau and J-M Péron (2009). Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo . PLoS One 4: e6278.
- Chamberlain G, J Fox, B Ashton and J Middleton (2007). Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem cells 25: 2739–2749.
- Haynesworth S, M Barer and A Caplan (1992). Cell surface antigens on human marrow-derived mesenchymal cells are detected by monoclonal antibodies. Bone 13: 69–80.
- Uccelli A, L Moretta and V Pistoia (2006). Immunoregulatory function of mesenchymal stem cells. European Journal of Immunology 36: 2566–2573.
- Rasmusson I (2006). Immune modulation by mesenchymal stem cells. Experimental cell research 312: 2169–2179.
- Nauta AJ and WE Fibbe (2007). Immunomodulatory properties of mesenchymal stromal cells. Blood 110: 3499–3506.
- Di Nicola M, C Carlo-Stella, M Magni, M Milanesi, PD Longoni, P Matteucci, S Grisanti and AM Gianni (2002). Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99: 3838–3843.
- Bartholomew A, C Sturgeon, M Siatskas, K Ferrer, K McIntosh, S Patil, W Hardy, S Devine, D Ucker and R Deans (2002). Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo . Experimental Hematology 30: 42–48.
- Soleymaninejadian E, K Pramanik and E Samadian (2012). Immunomodulatory properties of mesenchymal stem cells: cytokines and factors. American Journal of Reproductive Immunology 67: 1–8.
- Jorgensen C (2010). Mesenchymal stem cells immunosuppressive properties: is it specific to bone marrow-derived cells? Stem Cell Research and Therapy 1: 15.
- Rutella S, S Danese and G Leone (2006). Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 108: 1435–1440.
- Forbes SJ and PN Newsome (2012). New horizons for stem cell therapy in liver disease. Journal of hepatology 56: 496–499.
- Amariglio N, A Hirshberg, BW Scheithauer, Y Cohen, R Loewenthal, L Trakhtenbrot, N Paz, M Koren-Michowitz, D Waldman and L Leider-Trejo (2009). Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Medicine 6: e1000029.
- Blum B and N Benvenisty (2007). Clonal analysis of human embryonic stem cell differentiation into teratomas. Stem Cells 25: 1924–1930.
- Peng Y, S Huang, B Cheng, X Nie, J Enhe, C Feng and X Fu (2013). Mesenchymal stem cells: A revolution in therapeutic strategies of age-related diseases. Ageing Research Reviews 12: 103–115.
- Sharpless NE and RA DePinho (2007). How stem cells age and why this makes us grow old. Nature Reviews Molecular Cell Biology 8: 703–713.
- Sethe S, A Scutt and A Stolzing (2006). Aging of mesenchymal stem cells. Ageing Research Reviews 5: 91–116.
- Campisi J (2005). Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120: 513–522.
- Christensen BC, EA Houseman, CJ Marsit, S Zheng, MR Wrensch, JL Wiemels, HH Nelson, MR Karagas, JF Padbury and R Bueno (2009). Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS genetics 5: e1000602.
- Jakob F (2009). Clinical applications of mesenchymal stem cells. Bone 44: S206.
- Wang S, X Qu and RC Zhao (2012). Clinical applications of mesenchymal stem cells. Journal of Hematology and Oncology 5: 19.
- Liu L and TA Rando (2011). Manifestations and mechanisms of stem cell aging. The Journal of Cell Biology 193: 257–266.
- Eglen RM and T Reisine (2011). Screening for compounds that modulate epigenetic regulation of the transcriptome an overview. Journal of Biomolecular Screening 16: 1137–1152.
- Chen C-S (2002). Phorbol ester induces elevated oxidative activity and alkalization in a subset of lysosomes. BMC Cell Biology 3: 21.
- Baxter MA, RF Wynn, SN Jowitt, J Wraith, LJ Fairbairn and I Bellantuono (2004). Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells 22: 675–682.
- Martin JA and JA Buckwalter (2001). Roles of articular cartilage aging and chondrocyte senescence in the pathogenesis of osteoarthritis. The Iowa Orthopaedic Journal 21: 1.
- Parsch D, J Fellenberg, TH Brümmendorf, A-M Eschlbeck and W Richter (2004). Telomere length and telomerase activity during expansion and differentiation of human mesenchymal stem cells and chondrocytes. Journal of Molecular Medicine 82: 49–55.
- Yan X, S Ehnert, J Sanchez, G Damm, U Stöckle, P de Sousa and A Nüssler (2012). 436 Chemical modification epigenetically ‘renews'old human adipose derived mesenchymal stem cells and improves their differentiation into hepatocytes lineage. Journal of Hepatology 56: S173.
- Berdasco M and M Esteller (2012). Hot topics in epigenetic mechanisms of aging: 2011. Aging Cell 11: 181–186.
- Dai Q and C He (2011). Syntheses of 5-formyl-and 5-carboxyl-dC containing DNA oligos as potential oxidation products of 5-hydroxymethylcytosine in DNA. Organic Letters 13: 3446–3449.
- Thompson RF, G Atzmon, C Gheorghe, HQ Liang, C Lowes, JM Greally and N Barzilai (2010). Tissue-specific dysregulation of DNA methylation in aging. Aging Cell 9: 506–518.
- Yan X, S Ehnert, M Culmes, A Bachmann, C Seeliger, L Schyschka, Z Wang, A Rahmanian-Schwarz, U Stöckle, PA De Sousa, et al. (2014) 5-Azacytidine Improves the Osteogenic Differentiation Potential of Aged Human Adipose-Derived Mesenchymal Stem Cells by DNA Demethylation. PLoS one 9: e90846.
- Thomson JA, J Itskovitz-Eldor, SS Shapiro, MA Waknitz, JJ Swiergiel, VS Marshall and JM Jones (1998). Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147.
- Baxter MA, C Rowe, J Alder, S Harrison, KP Hanley, BK Park, NR Kitteringham, CE Goldring and NA Hanley (2010). Generating hepatic cell lineages from pluripotent stem cells for drug toxicity screening. Stem cell research 5: 4–22.
- Bone HK, AS Nelson, CE Goldring, D Tosh and MJ Welham (2011). A novel chemically directed route for the generation of definitive endoderm from human embryonic stem cells based on inhibition of GSK-3. Journal of Cell Science 124: 1992–2000.
- Kehat I, D Kenyagin-Karsenti, M Snir, H Segev, M Amit, A Gepstein, E Livne, O Binah, J Itskovitz-Eldor and L Gepstein (2001). Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. Journal of Clinical Investigation 108: 407–414.
- Schuldiner M and N Benvenisty (2003). Factors controlling human embryonic stem cell differentiation. Methods in Enzymology 365: 446–461.
- Spence JR, CN Mayhew, SA Rankin, MF Kuhar, JE Vallance, K Tolle, EE Hoskins, VV Kalinichenko, SI Wells and AM Zorn (2010). Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro . Nature 470: 105–109.
- Petit I, M Szyper-Kravitz, A Nagler, M Lahav, A Peled, L Habler, T Ponomaryov, RS Taichman, F Arenzana-Seisdedos and N Fujii (2002). G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nature Immunology 3: 687–694.
- Lévesque J-P, J Hendy, IG Winkler, Y Takamatsu and PJ Simmons (2003). Granulocyte colony-stimulating factor induces the release in the bone marrow of proteases that cleave c-KIT receptor (CD117) from the surface of hematopoietic progenitor cells. Experimental Hematology 31: 109–117.
- Ehnert S, M Glanemann, A Schmitt, S Vogt, N Shanny, NC Nussler, U Stöckle and A Nussler (2009). The possible use of stem cells in regenerative medicine: dream or reality? Langenbeck's Archives of Surgery 394: 985–997.
- Ebrahimian T, F Pouzoulet, C Squiban, V Buard, M André, B Cousin, P Gourmelon, M Benderitter, L Casteilla and R Tamarat (2009). Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing. Arteriosclerosis, Thrombosis, and Vascular Biology 29: 503–510.
- François S, M Mouiseddine, N Mathieu, A Semont, P Monti, N Dudoignon, A Saché, A Boutarfa, D Thierry and P Gourmelon (2007). Human mesenchymal stem cells favour healing of the cutaneous radiation syndrome in a xenogenic transplant model. Annals of hematology 86: 1–8.
- Stephenson E, CM Ogilvie, H Patel, G Cornwell, L Jacquet, N Kadeva, P Braude and D Ilic (2010). Safety paradigm: genetic evaluation of therapeutic grade human embryonic stem cells. Journal of The Royal Society Interface 7: S677–S688.
- Hidaka M, GN-C Su, JK-H Chen, K-i Mukaisho, T Hattori and G Yamamoto (2007). Transplantation of engineered bone tissue using a rotary three-dimensional culture system. In vitro Cellular and Developmental Biology – Animal 43: 49–58.
- He L, X Nan, Y Wang, L Guan, C Bai, S Shi, H Yuan, L Chen, D Liu and X Pei (2007). Full-thickness tissue engineered skin constructed with autogenic bone marrow mesenchymal stem cells. Science in China Series C: Life Sciences 50: 429–437.
- Goldring CE, PA Duffy, N Benvenisty, PW Andrews, U Ben-David, R Eakins, N French, NA Hanley, L Kelly and NR Kitteringham (2011). Assessing the safety of stem cell therapeutics. Cell Stem Cell 8: 618–628.
- Ben-David U and N Benvenisty (2011). The tumorigenicity of human embryonic and induced pluripotent stem cells. Nature Reviews Cancer 11: 268–277.
- Blum B and N Benvenisty (2008). The tumorigenicity of human embryonic stem cells. Advances in Cancer Research 100: 133–158.
- Drukker M and N Benvenisty (2004). The immunogenicity of human embryonic stem-derived cells. Trends in Biotechnology 22: 136–141.
- Swijnenburg R-J, S Schrepfer, JA Govaert, F Cao, K Ransohoff, AY Sheikh, M Haddad, AJ Connolly, MM Davis and RC Robbins (2008). Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts. Proceedings of the National Academy of Sciences 105: 12991–12996.
- Mackay IR (2000). Science, medicine, and the future: tolerance and autoimmunity. BMJ: British Medical Journal 321: 93.
- Martin GR and MJ Evans (1974). The morphology and growth of a pluripotent teratocarcinoma cell line and its derivatives in tissue culture. Cell 2: 163–172.
- Evans MJ and MH Kaufman (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature 292: 154–156.
- Reynolds BA and S Weiss (1992). Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255: 1707–1710.
- Thomson JA, J Kalishman, TG Golos, M Durning, CP Harris, RA Becker and JP Hearn (1995). Isolation of a primate embryonic stem cell line. Proceedings of the National Academy of Sciences 92: 7844–7848.
- Ahmad I, L Tang and H Pham (2000). Identification of neural progenitors in the adult mammalian eye. Biochemical and Biophysical Research Communications 270: 517–521.
- Toma JG, M Akhavan, KJ Fernandes, F Barnabé-Heider, A Sadikot, DR Kaplan and FD Miller (2001). Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nature Cell Biology 3: 778–784.
- Singh SK, ID Clarke, M Terasaki, VE Bonn, C Hawkins, J Squire and PB Dirks (2003). Identification of a cancer stem cell in human brain tumors. Cancer Research 63: 5821–5828.
- Al-Hajj M, MS Wicha, A Benito-Hernandez, SJ Morrison and MF Clarke (2003). Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences 100: 3983–3988.
- Takahashi K and S Yamanaka (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663–676.
- Amabile G and A Meissner (2009). Induced pluripotent stem cells: current progress and potential for regenerative medicine. Trends in Molecular Medicine 15: 59–68.
- Patel M and S Yang (2010). Advances in reprogramming somatic cells to induced pluripotent stem cells. Stem Cell Reviews and Reports 6: 367–380.
- Smukler SR, ME Arntfield, R Razavi, G Bikopoulos, P Karpowicz, R Seaberg, F Dai, S Lee, R Ahrens and PE Fraser (2011). The adult mouse and human pancreas contain rare multipotent stem cells that express insulin. Cell Stem Cell 8: 281–293.
- Minguell JJ, A Erices and P Conget (2001). Mesenchymal stem cells. Experimental Biology and Medicine 226: 507–520.
- Wagner W, F Wein, A Seckinger, M Frankhauser, U Wirkner, U Krause, J Blake, C Schwager, V Eckstein and W Ansorge (2005). Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Experimental Hematology 33: 1402–1416.