Abstract
Regenerative Medicine is a new, multidisciplinary field that combines expertise in biology, chemistry, engineering, materials, and medicine, to find solutions to some of the most challenging medical problems faced by humankind. Regenerative Medicine has the potential to impact the whole spectrum of health care, such as heart disease, emphysema, and diabetes. Regenerative Medicine employs various combinations of specially grown cells, tissues, and laboratory-made compounds to replace or amplify the body's natural healing process. The impact of Regenerative Medicine to the health care industry is likely to be comparable with that of antibiotics, vaccines and lately, monoclonal antibodies have had in clinical care. Regenerative Medicine is growing and maturing steadily; however, many challenges lie ahead. These include best cell source, most appropriate biomaterials, and reliable ways of expanding the cells and growing them in a three-dimensional environment (stem cell bioprocessing). This concise review deals with current achievements in the field, challenges that lie ahead and potential ways of having robust and reliable “off the shelf” cellular products.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- 2 (3) D:
-
2 (3) dimensional
- EC:
-
embryonal carcinoma
- ES:
-
embryonic stem
- EpiSC:
-
epiblast stem cells
- FITR:
-
Fourier iterative transform X-ray
- GMP:
-
good manufacture practice
- HARV:
-
high aspect ratio vessels
- HSCs:
-
hemopoietic stem cells
- ICM:
-
inner cell mass
- mESCs:
-
mouse embryonic stem cells
- MSCs:
-
mesenchymal stem cells
References
Dvir T, Benishti N, Shachar M, Cohen S 2006 A novel perfusion bioreactor providing a homogeneous milieu for tissue regeneration. Tissue Eng 12: 2843–2852
Christodoulou I, Buttery LD, Saravanapavan P, Tai G, Hench LL, Polak JM 2005 Dose- and time-dependent effect of bioactive gel-glass ionic-dissolution products on human fetal osteoblast-specific gene expression. J Biomed Mater Res B Appl Biomater 74: 529–537
Tsigkou O, Hench LL, Boccaccini AR, Polak JM, Stevens MM 2007 Enhanced differentiation and mineralization of human fetal osteoblasts on PDLLA containing Bioglass composite films in the absence of osteogenic supplements. J Biomed Mater Res A 80: 837–851
Christodoulou I, Buttery LD, Tai G, Hench LL, Polak JM 2006 Characterization of human fetal osteoblasts by microarray analysis following stimulation with 58S bioactive gel-glass ionic dissolution products. J Biomed Mater Res B Appl Biomater 77: 431–446
Guillot PV, Cui W, Fisk NM, Polak JM 2007 Stem cell differentiation and expansion for clinical applications of Tissue Engineering. J Cell Mol Med 11: 935–944
Lovell-Badge R 2007 Many ways to pluripotency. Nat Biotechnol 25: 1114–1116
Evans MJ, Kaufmann MH 1981 Establishment in culture of pluripotential cells from mouse embryos. Nature 292: 154–156
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM 1998 Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147
Brons IG, Smithers LE, Trotter MW, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes SM, Howlett SK, Clarkson A, Ahrlund-Richter L, Pedersen RA, Vallier L 2007 Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448: 191–195
Tesar PJ, Chenoweth JG, Brook FA, Davies TJ, Evans EP, Mack DL, Gardner RL, McKay RD 2007 New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448: 196–199
Takahashi K, Yamanaka S 2006 Induction of pluripotent stem cells form mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663–676
Okita K, Ichisaka T, Yamanaka S 2007 Generation of germline-competent induced pluripotent stem cells. Nature 448: 313–317
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S 2007 Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131: 861–872
Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA 2007 Induced pluripotent stem cell lines derived from human somatic cells. Science 318: 1917–20
Chien KR, Moretti A, Laugwitz K-L 2004 ES cells to the rescue. Science 306: 239–240
Manganas LN, Zhang X, Li Y, Hazel RD, Smith SD, Wagshul ME, Henn F, Benveniste H, Djuric PM, Enikolopov G, Maletic-Savatic M 2007 Magnetic resonance spectroscopy identifies progenitor cells in the live human brain. Science 318: 980–985
Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H 2007 Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449: 1003–1007
Watt FM, Lo Celso C, Silva-Vargas V 2006 Epidermal stem cells: an update. Curr Opin Genet Dev 16: 518–524
Phinney DG, Prockop DJ 2007 Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair—current views. Stem Cells 25: 2896–2902
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR 1999 Multilineage potential of adult human mesenchymal stem cells. Science 284: 143–147
Caplan AI 1994 The mesengenic process. Clin Plast Surg 21: 429–435
Rachakatla RS, Marini F, Weiss ML, Tamura M, Troyer D 2007 Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors. Cancer Gene Ther 14: 828–835
Weiss ML, Troyer DL 2006 Stem cells in the umbilical cord. Stem Cell Rev 2: 155–162
Appelbaum FR 2007 Hematopoietic-cell transplantation at 50. N Engl J Med 357: 1472–1475
Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR, McGlave PB, Wagner JE 2007 Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood 110: 3064–3070
Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L, Hofmann T 2002 Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc Natl Acad Sci USA 99: 8932–8937
Assmus B, Honold J, Schächinger V, Britten MB, Fischer-Rasokat U, Lehmann R, Teupe C, Pistorius K, Martin H, Abolmaali ND, Tonn T, Dimmeler S, Zeiher AM 2006 Transcoronary transplantation of progenitor cells after myocardial infarcation. N Engl J Med 355: 1222–1232
Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, Endresen K, Ilebekk A, Mangschau A, Fjeld JG, Smith HJ, Taraldsrud E, Grøgaard HK, Bjørnerheim R, Brekke M, Müller C, Hopp E, Ragnarsson A, Brinchmann JE, Forfang K 2006 Intracoronary injection of mononuclear bone-marrow cells in acute myocardial infarction. N Engl J Med 355: 1199–1209
Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Hölschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Süselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM, REPAIR-AMI Investigators 2006 Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 355: 1210–1221
Evans ND, Gentleman E, Polak JM 2006 Scaffolds for stem cells. Mater Today 9: 26–33
Langer R, Vacanti JP 1993 Tissue Engineering. Science 260: 920–926
Leor J, Amsalem Y, Cohen S 2005 Cells, scaffolds, and molecules for myocardial Tissue Engineering. Pharmacol Ther 105: 151–163
Hench LL 1998 Biomaterials: a forecast for the future. Biomaterials 19: 1419–1423
Xynos ID, Hukkanen MV, Batten JJ, Buttery LD, Hench LL, Polak JM 2000 Bioglass 45S5R stimulates osteoblast turnover and enhances bone formation in vitro: implications and applications for bone Tissue Engineering. Calcif Tissue Int 67: 321–329
Xynos ID, Edgar AJ, Buttery LD, Hench LL, Polak JM 2000 Ionic products of bioactive glass dissolution increase proliferation of human osteoblasts and induce insulin-like growth factor II mRNA expression and protein synthesis. Biochem Biophys Res Commun 276: 461–465
Xynos ID, Edgar AJ, Buttery LD, Hench LL, Polak JM 2001 Gene-expression profiling of human osteoblasts following treatment with the ionic products of Bioglass 45S5 dissolution. J Biomed Mater Res 55: 151–157
Hench LL, Polak JM 2002 Third-generation of biomedical materials. Science 295: 1014–1017
Smith AG 1991 Culture and differentiation of embryonic stem cells. J Tissue Cult Methods 13: 89–94
Yamada KM, Clark K 2002 Cell biology: survival in three dimensions. Nature 419: 790–791
Zandstra PW, Nagy A 2001 Stem cell bioengineering. Annu Rev Biomed Eng 3: 275–305
Martin I, Wendt D, Heberer M 2004 The role of bioreactors in Tissue Engineering. Trends Biotechnol 22: 80–86
Boudreault P, Tremblay JP, Pepin MF, Garnier A 2001 Scale-up of a myoblast culture process. J Biotechnol 91: 63–74
Liu JY, Hafner J, Dragieva G, Burg G 2004 Bioreactor microcarrier cell culture system (Bio-MCCS) for large-scale production of autologous melanocytes. Cell Transplant 13: 809–816
Kino-Oka M, Umegaki R, Taya M 2005 Bioreactor design for successive culture of anchorage-dependent cells operated in automated manner. Tissue Eng 11: 535–545
Monga SP, Hout MS, Baun MJ, Micsenyi A, Muller P, Tummalapalli L, Ranade AR, Luo JH, Strom SC, Gerlach JC 2005 Mouse fetal liver cells in artificial capillary beds in three-dimensional four-compartment bioreactors. Am J Pathol 167: 1279–1292
Youn BS, Sen A, Kallos MS, Behie LA, Girgis-Gabardo A, Kurpios N, Barcelon M, Hassell JA 2005 Large-scale expansion of mammary epithelial stem cell aggregates in suspension bioreactors. Biotechnol Prog 21: 984–993
Gilbertson JA, Sen A, Behie LA, Kallos MS 2006 Scaled-up production of mammalian neural precursor cell aggregates in computer-controlled suspension bioreactors. Biotechnol Bioeng 94: 783–792
Chen HC, Lee HP, Sung ML, Liao CJ, Hu YC 2004 A novel rotating-shaft bioreactor for two-phase cultivation of tissue-engineered cartilage. Biotechnol Prog 20: 1802–1809
Williams C, Wick TM 2004 Perfusion bioreactor for small diameter tissue-engineered arteries. Tissue Eng 10: 930–941
Mahmoudifar N, Doran PM 2005 Tissue Engineering of human cartilage and osteochondral composites using recirculation bioreactors. Biomaterials 26: 7012–7024
Janssen FW, Oostra J, Oorschot A, van Blitterswijk CA 2006 A perfusion bioreactor system capable of producing clinically relevant volumes of tissue-engineered bone: in vivo bone formation showing proof of concept. Biomaterials 27: 315–323
Song K, Yang Z, Liu T, Zhi W, Li X, Deng L, Cui Z, Ma X 2006 Fabrication and detection of tissue-engineered bones with bio-derived scaffolds in a rotating bioreactor. Biotechnol Appl Biochem 45: 65–74
Mol A, Driessen NJ, Rutten MC, Hoerstrup SP, Bouten CV, Baaijens FP 2005 Tissue Engineering of human heart valve leaflets: a novel bioreactor for a strain-based conditioning approach. Ann Biomed Eng 33: 1778–1788
Seidel JO, Pei M, Gray ML, Langer R, Freed LE, Vunjak-Novakovic G 2004 Long-term culture of tissue engineered cartilage in a perfused chamber with mechanical stimulation. Biorheology 41: 445–458
Jeong SI, Kwon JH, Lim JI, Cho SW, Jung Y, Sung WJ, Kim SH, Kim YH, Lee YM, Kim BS, Choi CY, Kim SJ 2005 Mechano-active Tissue Engineering of vascular smooth muscle using pulsatile perfusion bioreactors and elastic PLCL scaffolds. Biomaterials 26: 1405–1411
Randle WL, Cha JM, Hwang YS, Chan KL, Kazarian SG, Polak JM, Mantalaris A 2007 Integrated 3D expansion and osteogenic differentiation of murine embryonic stem cells. Tissue Eng 13: 2957–2970
Sun AM, Parisius W, Macmorine H, Sefton MV, Stone R 1980 An artificial pancreas containing cultured islets of Langerhans. Artif Organs 4: 275–278
Sefton MV, Broughton RL 1982 Microencapsulation of erythrocytes. Biochim Biophys Acta 717: 473–477
Magyar JP, Nemir M, Ehler E, Suter N, Perriard JC, Eppenberger HM 2001 Mass production of embryoid bodies in microbeads. Ann N Y Acad Sci 944: 135–143
Foster JL, Williams G, Willimas LH, Tuch BE 2007 Differentiation of transplanted microencapsulated fetal pancreatic cells. Transplantation 83: 1440–1448
Awad HA, Wickham MQ, Leddy HA, Gimble JM, Guilak F 2004 Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. Biomaterials 25: 3211–3222
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Polak, J., Mantalaris, S. Stem Cells Bioprocessing: An Important Milestone to Move Regenerative Medicine Research Into the Clinical Arena. Pediatr Res 63, 461–466 (2008). https://doi.org/10.1203/PDR.0b013e31816a8c1c
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/PDR.0b013e31816a8c1c
This article is cited by
-
Development of a Novel Perfusion Rotating Wall Vessel Bioreactor with Ultrasound Stimulation for Mass-Production of Mineralized Tissue Constructs
Tissue Engineering and Regenerative Medicine (2022)