Skip to main content

What Is the Future for Stem Cell Research?

Whether Entity or Function?

  • Chapter
Stem Cells Handbook

Abstract

The goal of the intense research on stem cells is for human application. Recently, knowledge of stem cells has progressed rapidly and experimental therapies are already in clinical trials. However, for more far reaching application and successful therapy much more remains to be learned about stem cells. There are many more questions than answers. What is a stem cell? What different kinds are there? Can they be obtained and manipulated? What are the lineages that derive from stem cells, and how plastic are cells in a lineage? Are there circulating stem cells in adults? Do they participate in repair of injury? What type of stem cell is most appropriate for a given clinical application? New technologies need to be developed to apply to stem cells for effective gene delivery. What role, if any, does fusion of stem cells play in tissue regeneration? Can the differentiation potential of stem cells at different stages of determination be used to select cells for specific clinical applications? What are the signals that recruit, activate, and induce differentiation in stem cells? What are the signaling pathways for activation and differentiation of stem cells, and can they be manipulated to advantage? How can stem cells be used to understand carcinogenesis and developmental abnormalities? Are embryonic stem cells, which have the potential to produce progeny that can differentiate into any adult tissues the best cells for therapeutic use? Or in some instances, are adult stem cells resident in adult tissues or circulating adult bone marrow derived cells a better choice? How can immune rejection of transplanted cells be avoided or prevented? Will therapeutic cloning, whereby transfer of somatic nuclei to provide an embryonic cell line that matches the patient, become clinically applicable? Can embryonic germ cells be used to greater advantage that embryonic stem cells? Will adult stem cells, if they can be isolated and cultured, be a better choice for selected use, for example, in replacing cells in a specific damaged organ. Are there adult multipotent stem cells or can adult tissue-determined stem cells transdifferentiate to another tissue cell type? If so, how can this be controlled? Does fusion play a role in functional stem cell plasticity and can a way to use fusion to direct tissue repair or replacement be devised? Do human somatic cells have the capacity for dedifferentiation, such as found during regeneration of tissues in amphibians? Can this phenomenon be applied to mammalian tissues and eventually used clinically? How can genetic modification of human embryonic or adult stem cells be improved and applied? The potential of stem cell therapy has great promise and is only limited by our incomplete knowledge of what stem cells are and how they function.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 199.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 259.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aboody, K. S., Brown, A., Rainov, N. G., et al. (2000) Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc. Natl. Acad. Sci. USA 97:12,846–12,851.

    Article  CAS  Google Scholar 

  • Alison, M. R., Poulsom, R., Jeffery, R., et al. (2000) Hepatocytes from non-hepatic adult stem cells. Nature 406:257.

    Article  PubMed  CAS  Google Scholar 

  • Amit, M., Carpenter, M. K., Inokuma, M. S., et al. (2000) Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture. Dev. Biol. 227:271–278.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, D. J., Gage, F. H., and Weissman, I. L. (2001) Can stem cells cross lineage boundaries? Nat. Med. 7:393–395.

    Article  PubMed  CAS  Google Scholar 

  • Barr, E., and Leiden, J. M. (1991) Systemic delivery of recombinant proteins by genetically modified myoblasts. Science 254:1507–1509.

    Article  PubMed  CAS  Google Scholar 

  • Bjornson, C. R., Rietze, R. L., Reynolds, B. A., Magli, M. C., and Vescovi, A. L. (1999) Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 283:534–537.

    Article  PubMed  CAS  Google Scholar 

  • Blau, H. M. (2002) A twist of fate. Nature 419:437.

    Article  PubMed  CAS  Google Scholar 

  • Blau, H. M., and Baltimore, D. (1991) Differentiation requires continuous regulation. J. Cell Biol. 112:781–783.

    Article  PubMed  CAS  Google Scholar 

  • Blau, H. M., Brazelton, T. R., and Weimann, J. M. (2001) The evolving concept of a stem cell: entity or function? Cell 105:829–841.

    Article  PubMed  CAS  Google Scholar 

  • Blau, H. M., Chiu, C. P., and Webster, C. (1983) Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell 32:1171–1180.

    Article  PubMed  CAS  Google Scholar 

  • Blau, H. M., Pavlath, G. K., Hardeman, E. C., et al. (1985) Plasticity of the differentiated state. Science 230:758–766.

    Article  PubMed  CAS  Google Scholar 

  • Blau, H. M., and Springer, M. L. (1995a) Gene therapy-a novel form of drug delivery. N. Engl. J. Med. 333:1204–1207.

    Article  PubMed  CAS  Google Scholar 

  • Blau, H. M., and Springer, M. L. (1995b) Muscle-mediated gene therapy. N. Engl. J. Med. 333:1554–1556.

    Article  PubMed  CAS  Google Scholar 

  • Brazelton, T. R., Rossi, F. M., Keshet, G. I., and Blau, H. M. (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290:1775–1779.

    Article  PubMed  CAS  Google Scholar 

  • Brazelton, T. R., Rossi, F. M., Keshet, G. I., and Blau, H. M. (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290:1775–1779.

    Article  PubMed  CAS  Google Scholar 

  • Chambers, I., Colby, D., Robertson, M., et al. (2003) Functional expression cloning of nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113:643–655.

    Article  PubMed  CAS  Google Scholar 

  • Chiu, C. P., and Blau, H. M. (1984) Reprogramming cell differentiation in the absence of DNA synthesis. Cell 37:879–887.

    Article  PubMed  CAS  Google Scholar 

  • Clarke, D. L., Johansson, C. B., Wilbertz, J., et al. (2000) Generalized potential of adult neural stem cells. Science 288:1660–1663.

    Article  PubMed  CAS  Google Scholar 

  • Dani, C., Chambers, I., Johnstone, S., et al. (1998) Paracrine induction of stem cell renewal by LIF-deficient cells: a new ES cell regulatory pathway. Dev. Biol. 203:149–162.

    Article  PubMed  CAS  Google Scholar 

  • Dhawan, J., Pan, L. C., Pavlath, G. K., Travis, M. A., Lanctot, A. M., and Blau, H. M. (1991) Systemic delivery of human growth hormone by injection of genetically engineered myoblasts. Science 254:1509–1512.

    Article  PubMed  CAS  Google Scholar 

  • Dick, J. E., Magli, M. C., Huszar, D., Phillips, R. A., and Bernstein, A. (1985) Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/W mice. Cell 42:71–79.

    Article  PubMed  CAS  Google Scholar 

  • Ferrari, G., Cusella-De Angelis, G., Coletta, M., et al. (1998) Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279:1528–1530.

    Article  PubMed  CAS  Google Scholar 

  • Gussoni, E., Soneoka, Y., Strickland, C. D., et al. (1999) Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401:390–394.

    PubMed  CAS  Google Scholar 

  • Itskovitz-Eldor, J., Schuldiner, M., Karsenti, D., et al. (2000) Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol. Med. 6:88–95.

    PubMed  CAS  Google Scholar 

  • Jackson, K. A., Majka, S. M., Wang, H., et al. (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J. Clin. Invest. 107:1395–1402.

    Article  PubMed  CAS  Google Scholar 

  • Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., et al. (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418: 41–49.

    Article  PubMed  CAS  Google Scholar 

  • Kaufman, D. S., Hanson, E. T., Lewis, R. L., Auerbach, R., and Thomson, J. A. (2001) Hematopoietic colony-forming cells derived from human embryonic stem cells. Proc. Natl. Acad. Sci. USA 98:10,716–10,721.

    Article  CAS  Google Scholar 

  • Kielman, M. F., Rindapaa, M., Gaspar, C., et al. (2002) Apc modulates embryonic stem-cell differentiation by controlling the dosage of betacatenin signaling. Nat. Genet. 32:594–605.

    Article  PubMed  CAS  Google Scholar 

  • Kim, J. H., Auerbach, J. M., Rodriguez-Gomez, J. A., et al. (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418:50–56.

    Article  PubMed  CAS  Google Scholar 

  • Kocher, A. A., Schuster, M. D., Szabolcs, M. J., et al. (2001) Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat. Med. 7:430–436.

    Article  PubMed  CAS  Google Scholar 

  • Kondo, T., and Raff, M. (2000) Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289: 1754–1757.

    Article  PubMed  CAS  Google Scholar 

  • Krause, D. S., Theise, N. D., Collector, M. I., et al. (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105:369–377.

    Article  PubMed  CAS  Google Scholar 

  • LaBarge, M. A. and Blau, H. M. (2002) Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell 111:589–601.

    Article  PubMed  CAS  Google Scholar 

  • Lagasse, E., Connors, H., Al-Dhalimy, M., et al. (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat. Med. 6:1229–1234.

    Article  PubMed  CAS  Google Scholar 

  • Laurencin, C. T., Attawia, M. A., Lu, L. Q., et al. (2001) Poly(lactideco-glycolide)/hydroxyapatite delivery of BMP-2-producing cells: a regional gene therapy approach to bone regeneration. Biomaterials 22:1271–1277.

    Article  PubMed  CAS  Google Scholar 

  • Lovell-Badge, R. (2001) The future for stem cell research. Nature 414: 88–91.

    Article  PubMed  CAS  Google Scholar 

  • McDonald, J. W., Liu, X. Z., Qu, Y., et al. (1999) Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat. Med. 5:1410–1412.

    Article  PubMed  CAS  Google Scholar 

  • Mezey, E., Chandross, K. J., Harta, G., Maki, R. A., and McKercher, S. R. (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290:1779–1782.

    Article  PubMed  CAS  Google Scholar 

  • Min, J. Y., Yang, Y., Converso, K. L., et al. (2002) Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats. J. Appl. Physiol. 92:288–296.

    Article  PubMed  Google Scholar 

  • Mitsui, K., Tokuzawa, Y., Itoh, H., et al. (2003) The homeoprotein nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113:631–642.

    Article  PubMed  CAS  Google Scholar 

  • Mohajeri, M. H., Figlewicz, D. A., and Bohn, M. C. (1999) Intramuscular grafts of myoblasts genetically modified to secrete glial cell linederived neurotrophic factor prevent motoneuron loss and disease progression in a mouse model of familial amyotrophic lateral sclerosis. Hum. Gene Ther. 10:1853–1866.

    Article  PubMed  CAS  Google Scholar 

  • Nichols, J., Zevnik, B., Anastassiadis, K., et al. (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95:379–391.

    Article  PubMed  CAS  Google Scholar 

  • Niwa, H., Burdon, T., Chambers, I., and Smith, A. (1998) Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev. 12:2048–2060.

    Article  PubMed  CAS  Google Scholar 

  • Nolta, J. A., Dao, M. A., Wells, S., Smogorzewska, E. M., and Kohn, D. B. (1996) Transduction of pluripotent human hematopoietic stem cells demonstrated by clonal analysis after engraftment in immunedeficient mice. Proc. Natl. Acad. Sci. USA 93:2414–2419.

    Article  PubMed  CAS  Google Scholar 

  • Odelberg, S. J., Kollhoff, A., and Keating, M. T. (2000) Dedifferentiation of mammalian myotubes induced by msxl. Cell 103:1099–1109.

    Article  PubMed  CAS  Google Scholar 

  • Odorico, J. S., Kaufman, D. S., and Thomson, J. A. (2001) Multilineage differentiation from human embryonic stem cell lines. Stem Cells 19: 193–204.

    Article  PubMed  CAS  Google Scholar 

  • Orlic, D., Kajstura, J., Chimenti, S., et al. (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705.

    Article  PubMed  CAS  Google Scholar 

  • Osawa, M., Hanada, K., Hamada, H., and Nakauchi, H. (1996) Longterm lymphohematopoietic reconstitution by a single CD34-low/ negative hematopoietic stem cell. Science 273:242–245.

    Article  PubMed  CAS  Google Scholar 

  • Ozawa, C. R., Springer, M. L., and Blau, H. M. (2000a) Ex vivo gene therapy using myoblasts and regulatable retroviral vectors. In Gene Therapy: Therapeutic Mechanisms and Strategies, (N. S. Templeton, and D. D. Lasic, eds.) Marcel Dekker, New York, NY, pp. 61–80.

    Google Scholar 

  • Ozawa, C. R., Springer, M. L., and Blau, H. M. (2000b) A novel means of drug delivery: myoblast-mediated gene therapy and regulatable retroviral vectors. Annu. Rev. Pharmacol. Toxicol. 40:295–317.

    Article  PubMed  CAS  Google Scholar 

  • Park, F., Ohashi, K., Chiu, W., Naldini, L., and Kay, M. A. (2000) Efficient lentiviral transduction of liver requires cell cycling in vivo. Nat. Genet. 24:49–52.

    Article  PubMed  CAS  Google Scholar 

  • Partridge, T. A. (2003) Stem cell route to neuromuscular therapies. Muscle Nerve 27:133–141.

    Article  PubMed  Google Scholar 

  • Pereira, R. F., Halford, K. W., O’Hara, M. D., et al. (1995) Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc. Natl. Acad. Sci. USA 92:4857–4861.

    Article  PubMed  CAS  Google Scholar 

  • Pereira, R. F., O’Hara, M. D., Laptev, A. V., et al. (1998) Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Proc. Natl. Acad. Sci. USA 95:1142–1147.

    Article  PubMed  CAS  Google Scholar 

  • Rathjen, P. D., Lake, J., Whyatt, L. M., Bettess, M. D., and Rathjen, J. (1998) Properties and uses of embryonic stem cells: prospects for application to human biology and gene therapy. Reprod. Fertil. Dev. 10:31–47.

    Article  PubMed  CAS  Google Scholar 

  • Reik, W., Dean, W., and Walter, J. (2001) Epigenetic reprogramming in mammalian development. Science 293:1089–1093.

    Article  PubMed  CAS  Google Scholar 

  • Reya, T., Duncan, A. W., Ailles, L., et al. (2003) A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423:409–414.

    Article  PubMed  CAS  Google Scholar 

  • Reyes, M., Dudek, A., Jahagirdar, B., Koodie, L., Marker, P. H., and Verfaillie, C. M. (2002) Origin of endothelial progenitors in human postnatal bone marrow. J. Clin. Invest. 109:337–346.

    PubMed  CAS  Google Scholar 

  • Reyes, M., Lund, T., Lenvik, T., Aguiar, D., Koodie, L., and Verfaillie, C. M. (2001) Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood 98:2615–2625.

    Article  PubMed  CAS  Google Scholar 

  • Rheinwald, J. G., and Green, H. (1975) Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell 6:331–343.

    Article  PubMed  CAS  Google Scholar 

  • Rideout, W. M., 3rd, Hochedlinger, K., Kyba, M., Daley, G. Q., and Jaenisch, R. (2002) Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell 109:17–27.

    Article  PubMed  CAS  Google Scholar 

  • Seale, P., Sabourin, L. A., Girgis-Gabardo, A., Mansouri, A., Gruss, P., and Rudnicki, M. A. (2000) Pax7 is required for the specification of myogenic satellite cells. Cell 102:777–786.

    Article  PubMed  CAS  Google Scholar 

  • Shamblott, M. J., Axelman, J., Littlefield, J. W., et al. (2001) Human embryonic germ cell derivatives express a broad range of developmentally distinct markers and proliferate extensively in vitro. Proc. Natl. Acad. Sci. USA 98:113–118.

    Article  PubMed  CAS  Google Scholar 

  • Shamblott, M. J., Axelman, J., Wang, S., et al. (1998) Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc. Natl. Acad. Sci. USA 95:13,726–13,731.

    Article  CAS  Google Scholar 

  • Springer, M. L., Chen, A. S., Kraft, P. E., Bednarski, M., and Blau, H. M. (1998) VEGF gene delivery to muscle: Potential role for vasculogenesis in adults. Mol. Cell 2:549–558.

    Article  PubMed  CAS  Google Scholar 

  • Surani, M. A. (2001) Reprogramming of genome function through epigenetic inheritance. Nature 414:122–128.

    Article  PubMed  CAS  Google Scholar 

  • Szilvassy, S. J., Fraser, C. C., Eaves, C. J., Lansdorp, P. M., Eaves, A. C., and Humphries, R. K. (1989) Retrovirus-mediated gene transfer to purified hemopoietic stem cells with long-term lympho-myelopoietic repopulating ability. Proc. Natl. Acad. Sci. USA 86:8798–8802.

    Article  PubMed  CAS  Google Scholar 

  • Terada, N., Hamazaki, T., Oka, M., et al. (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416: 542–545.

    Article  PubMed  CAS  Google Scholar 

  • Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., et al. (1998) Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147.

    Article  PubMed  CAS  Google Scholar 

  • Thomson, J. A., Kalishman, J., Gois, T. G., et al. (1995) Isolation of a primate embryonic stem cell line. Proc. Natl. Acad. Sci. USA 92: 7844–7848.

    Article  PubMed  CAS  Google Scholar 

  • Toma, J. G., Akhavan, M., Fernandes, K. J., et al. (2001) Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat. Cell Biol. 3:778–784.

    Article  PubMed  CAS  Google Scholar 

  • van Praag, H., Schinder, A. F., Christie, B. R., Toni, N., Palmer, T. D., and Gage, F. H. (2002) Functional neurogenesis in the adult hippocampus. Nature 415:1030–1034.

    Article  PubMed  Google Scholar 

  • Verfaillie, C. M., Pera, M. F., and Lansdorp, P. M. (2002) Stem cells: hype and reality. Hematology (Am. Soc. Hematol. Educ. Program):369–391.

    Google Scholar 

  • Waldmann, H. (2001) Therapeutic approaches for transplantation. Curr. Opin. Immunol. 13:606–610.

    Article  PubMed  CAS  Google Scholar 

  • Weimann, J. M., Charlton, C. A., Brazelton, T. R., Hackman, R. C., and Blau, H. M. (2003) Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains. Proc. Natl. Acad. Sci. USA 100:2088–2093.

    Article  PubMed  CAS  Google Scholar 

  • Willert, K., Brown, J. D., Danenberg, E., et al. (2003) Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423: 448–452.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, S. I., Rydstrom, A., Trimborn, T., et al. (2001) The status of Wnt signalling regulates neural and epidermal fates in the chick embryo. Nature 411:325–330.

    Article  PubMed  CAS  Google Scholar 

  • Ying, Q. L., Nichols, J., Evans, E. P., and Smith, A. G. (2002) Changing potency by spontaneous fusion. Nature 416:545–548.

    Article  PubMed  CAS  Google Scholar 

  • Zuk, P. A., Zhu, M., Mizuno, H., et al. (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7:211–228.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Doyonnas, R., Blau, H.M. (2004). What Is the Future for Stem Cell Research?. In: Sell, S. (eds) Stem Cells Handbook. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-411-5_43

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-411-5_43

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-367-1

  • Online ISBN: 978-1-59259-411-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics