Stem Cells and Regenerative Medicine

  • Mohan C. Vemuri
  • Chellu S. Chetty
Part of the Springer Protocols Handbooks book series (SPH)

1. Introduction

Stem cells and regenerative medicine is a rapidly progressing science that addresses the use of stem cells via cell therapy for human diseases. Successful use of stem cells in regenerative medicine depends on two important features of stem cells; a) stem cells can proliferate and self renew almost indefinitely, and b) they can differentiate into specialized cell types that make up tissues such as pancreas, heart, liver, blood, and others. Further, stem cells can be engineered to replace worn-out cells and to regenerate damaged tissue. These advances open up new ways of stem cell based treatment through regenerative medicine and tissue engineering.

2. Types of Stem Cells

There are two types of stem cells, embryonic stem cells and adult stem cells. Embryonic stem cells (ESC), derived from an early stage embryo such as blasto-cyst are the most primitive, unspecialized, and pluripotent cells. Pluripotent stem cells can become any type of cell in the epidermal, endodermal,...


Stem Cell Neural Stem Cell Mesenchymal Stromal Cell Adult Stem Cell Stem Cell Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Divya Vemuri for reading and editing the manuscript.


  1. 1.
    Thomson JA, Itskovitz-Eldor J, Shapiro SS et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147PubMedCrossRefGoogle Scholar
  2. 2.
    Vallier L, Alexander M, Pedersen RA (2005) Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells. J Cell Sci 118:4495–4509PubMedCrossRefGoogle Scholar
  3. 3.
    Levenstein ME, Ludwig TE, Xu RH et al (2006) Basic fibroblast growth factor support of human embryonic stem cell self-renewal. Stem Cells 24:568–574PubMedCrossRefGoogle Scholar
  4. 4.
    Wang G, Zhang H, Zhao Y et al (2005) Noggin and bFGF cooperate to maintain the pluripotency of human embryonic stem cells in the absence of feeder layers. Biochem Biophys Res Commun 330:934–42PubMedCrossRefGoogle Scholar
  5. 5.
    Xu C, Rosler E, Jiang J et al (2005) Basic fibroblast growth factor supports undif-ferentiated human embryonic stem cell growth without conditioned medium. Stem Cells 23:315–323PubMedCrossRefGoogle Scholar
  6. 6.
    Hoffman LM, Carpenter MK (2005) Characterization and culture of human embryonic stem cells. Nat Biotechnol 23:699–708PubMedCrossRefGoogle Scholar
  7. 7.
    Terskikh AV, Bryant PJ, Schwartz PH (2006) Mammalian stem cells. Pediatr Res 59:13R–20RPubMedCrossRefGoogle Scholar
  8. 8.
    Bryder D, Rossi DJ, Weissman IL (2006) Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol 169:338–346PubMedCrossRefGoogle Scholar
  9. 9.
    Bhattacharya D, Rossi DJ, Bryder D et al (2006) Purified hematopoietic stem cell engraftment of rare niches corrects severe lymphoid deficiencies without host conditioning. J Exp Med 203:73–85PubMedCrossRefGoogle Scholar
  10. 10.
    Bhattacharya D, Bryder D, Rossi DJ et al (2006) Rapid lymphocyte reconstitu-tion of unconditioned immunodeficient mice with non-self-renewing multipotent hematopoietic progenitors. Cell Cycle 5:1135–1139PubMedCrossRefGoogle Scholar
  11. 11.
    Parkman R, Cohen G, Carter SL et al (2006) Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation. Biol Blood Marrow Transplant 12:919–927CrossRefGoogle Scholar
  12. 12.
    Crooks GM, Weinberg K, Mackall C (2006) Immune reconstitution: from stem cells to lymphocytes. Biol Blood Marrow Transplant 12:42–46PubMedCrossRefGoogle Scholar
  13. 13.
    Kirouac DC, Zandstra PW (2006) Understanding cellular networks to improve hematopoietic stem cell expansion cultures. Curr Opin Biotechnol 17:538–547PubMedCrossRefGoogle Scholar
  14. 14.
    Suzuki T, Yokoyama Y, Kumano K et al (2006) Highly efficient ex vivo expansion of human hematopoietic stem cells using Delta11-Fc chimeric protein. Stem Cells 24:2456–2465PubMedCrossRefGoogle Scholar
  15. 15.
    Madlambayan GJ, Rogers I, Purpura KA et al (2006) Clinically relevant expansion of hematopoietic stem cells with conserved function in a single-use, closed-system bioprocess. Biol Blood Marrow Transplant 12:1020–1030PubMedCrossRefGoogle Scholar
  16. 16.
    Yao CL, Feng YH, Lin XZ et al (2006) Characterization of serum-free ex vivo-expanded hematopoietic stem cells derived from human umbilical cord blood CD133(+) cells. Stem Cells Dev 15:70–78PubMedCrossRefGoogle Scholar
  17. 17.
    Gordon M Y, Levicar N, Pai M et al (2006) Characterization and clinical application of human CD34² stem/progenitor cell populations mobilized into the blood by granulocyte colony-stimulating factor. Stem Cells 24:1822–1830PubMedCrossRefGoogle Scholar
  18. 18.
    Majumdar MK, Keane-Moore M, Buyaner D et al (2003) Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 10:228–241PubMedCrossRefGoogle Scholar
  19. 19.
    Magne D, Vinatier C, Julien M et al (2005) Mesenchymal stem cell therapy to rebuild cartilage. Trends Mol Med 11:519–526PubMedCrossRefGoogle Scholar
  20. 20.
    Tocci A, Forte L (2003) Mesenchymal stem cell: use and perspectives. Hematol J 4:92–6PubMedCrossRefGoogle Scholar
  21. 21.
    Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allo-geneic immune cell responses. Blood 105:1815–1822PubMedCrossRefGoogle Scholar
  22. 22.
    Liechty KW, Mackenzie TC, Shaaban AF et al (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6:1282–1286PubMedCrossRefGoogle Scholar
  23. 23.
    Meuleman N, Tondreau T, Delforge A et al (2006) Human marrow mesenchymal stem cell culture: serum-free medium allows better expansion than classical alpha-MEM medium. Eur J Haematol 76:309–316PubMedCrossRefGoogle Scholar
  24. 24.
    Muller I, Kordowich S, Holzwarth C et al (2006) Animal serum-free culture conditions for isolation and expansion of multipotent mesenchymal stromal cells from human BM. Cytotherapy 8:437–444PubMedCrossRefGoogle Scholar
  25. 25.
    Sotiropoulou PA, Perez SA, Salagianni M et al (2006) Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells 24:462–471PubMedCrossRefGoogle Scholar
  26. 26.
    Dominici M, Hofmann TJ, Horwitz EM (2001) Bone marrow mesenchymal cells: biological properties and clinical applications. J Biol Regul Homeost Agents 15:28–37PubMedGoogle Scholar
  27. 27.
    Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317PubMedCrossRefGoogle Scholar
  28. 28.
    Martinez-Serrano A, Rubio FJ, Navarro B et al (2001) Human neural stem and progenitor cells: in vitro and in vivo properties, and potential for gene therapy and cell replacement in the CNS. Curr Gene Ther 1:279–299PubMedCrossRefGoogle Scholar
  29. 29.
    Merkle FT, Alvarez-Buylla A (2006) Neural stem cells in mammalian development. Curr Opin Cell Biol 18:704–709PubMedCrossRefGoogle Scholar
  30. 30.
    Galvin KA, Jones DG (2002) Adult human neural stem cells for cell-replacement therapies in the central nervous system. Med J Aust 177:316–318PubMedGoogle Scholar
  31. 31.
    Vescovi AL, Parati EA, Gritti A et al (1999) Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation. Exp Neurol 156:71–83PubMedCrossRefGoogle Scholar
  32. 32.
    Villa A, Snyder EY, Vescovi A et al (2000) Establishment and properties of a growth factor-dependent, perpetual neural stem cell line from the human CNS. Exp Neurol 161:67–84PubMedCrossRefGoogle Scholar
  33. 33.
    Svendsen CN, Ter Borg MG, Armstrong RJ et al (1998) A new method for the rapid and long term growth of human neural precursor cells. J Neurosci Methods 85:141–152PubMedCrossRefGoogle Scholar
  34. 34.
    Cai J, Limke TL, Ginis I et al (2003) Identifying and tracking neural stem cells. Blood Cells Mol Dis 31:18–27PubMedCrossRefGoogle Scholar
  35. 35.
    Mori H, Ninomiya K, Kino-Oka M et al (2006) Effect of neurosphere size on the growth rate of human neural stem/progenitor cells. J Neurosci Res 84:1682–1691PubMedCrossRefGoogle Scholar
  36. 36.
    Ellis P, Fagan BM, Magness ST et al (2004) SOX2, a persistent marker for multipo-tential neural stem cells derived from embryonic stem cells, the embryo or the adult. Dev Neurosci 26:148–165PubMedCrossRefGoogle Scholar
  37. 37.
    Dupin E, Real C, Ledouarin N. (2001) The neural crest stem cells: control of neural crest cell fate and plasticity by endothelin-3. An Acad Bras Cienc 73:533–545PubMedGoogle Scholar
  38. 38.
    Moody SA, Je HS (2002) Neural induction, neural fate stabilization, and neural stem cells. Scientific WorldJournal 2:1147–1166Google Scholar
  39. 39.
    Cai J, Shin S, Wright L et al (2006) Massively parallel signature sequencing profiling of fetal human neural precursor cells. Stem Cells Dev 15:232–244PubMedCrossRefGoogle Scholar
  40. 40.
    Kassem M (2006) Stem cells: potential therapy for age-related diseases. Ann N Y Acad Sci 1067:436–442PubMedCrossRefGoogle Scholar
  41. 41.
    Yates F, Daley GQ (2006) Progress and prospects: gene transfer into embryonic stem cells. Gene Ther 13:1431–1439PubMedCrossRefGoogle Scholar
  42. 42.
    Peranteau WH, Endo M, Adibe OO et al (2006) CD26 inhibition enhances allogeneic donor cell homing and engraftment after in utero hematopoietic cell transplantation. Blood 108:4268–4274PubMedCrossRefGoogle Scholar
  43. 43.
    Tuch BE (2006) Stem cells – a clinical update. Aust Fam Physician 35:719–721PubMedGoogle Scholar
  44. 44.
    Van Laar JM, Tyndall A (2006) Adult stem cells in the treatment of autoimmune diseases. Rheumatology (Oxford) 45:1187–1193CrossRefGoogle Scholar
  45. 45.
    Eapen M, Rubinstein P, Zhang MJ et al (2007) Comparable long-term survival after unrelated and HLA-matched sibling donor hematopoietic stem cell transplantations for acute leukemia in children younger than 18 months. J Clin Oncol 24:145–151CrossRefGoogle Scholar
  46. 46.
    Paul G, Ahn YH, Li JY et al (2006) Transplantation in Parkinson's disease: the future looks bright. Adv Exp Med Biol 557:221–248PubMedCrossRefGoogle Scholar
  47. 47.
    Iacovitti L, Donaldson AE, Marshall CE et al (2007) A protocol for the differentiation of human embryonic stem cells into dopaminergic neurons using only chemically defined human additives: studies in vitro and in vivo. Brain Res 112:19–25CrossRefGoogle Scholar
  48. 48.
    Goldman SA, Windrem MS (2006) Cell replacement therapy in neurological disease. Philos Trans R Soc Lond B Biol Sci 361:1463–1475PubMedCrossRefGoogle Scholar
  49. 49.
    Snyder BJ, Olanow CW (2005) Stem cell treatment for Parkinson's disease: an update for 2005 Curr Opin Neurol 18:376–385PubMedCrossRefGoogle Scholar
  50. 50.
    Correia AS, Anisimov SV, Li JY et al (2005) Stem cell-based therapy for Parkinson's disease. Ann Med 37:487–498PubMedCrossRefGoogle Scholar
  51. 51.
    Pineda JR, Rubio N, Akerud P et al (2007) Neuroprotection by GDNF-secreting stem cells in a Huntington's disease model: optical neuroimage tracking of brain-grafted cells. Gene Ther 14:118–128PubMedGoogle Scholar
  52. 52.
    Okano H (2006) Adult neural stem cells and central nervous system repair. Ernst Schering Res Found Workshop 215–228Google Scholar
  53. 53.
    Torella D, Ellison GM, Mendez-Ferrer S et al (2006) Resident human cardiac stem cells: role in cardiac cellular homeostasis and potential for myocardial regeneration. Nat Clin Pract Cardiovasc Med 3 Suppl 1:S8–13PubMedCrossRefGoogle Scholar
  54. 54.
    Boyle AJ, Whitbourn R, Schlicht S et al (2006) Intra-coronary high-dose CD34+ stem cells in patients with chronic ischemic heart disease: a 12-month follow-up. Int J Cardiol 109:21–27PubMedCrossRefGoogle Scholar
  55. 55.
    Gallo P, Peschle C, Condorelli G (2006) Sources of cardiomyocytes for stem cell therapy: an update. Pediatr Res 59:79R–83RPubMedCrossRefGoogle Scholar
  56. 56.
    Saha M, Ferro A (2006) Cardiac stem cell therapy: present and future. Br J Clin Pharmacol 61:727–729PubMedCrossRefGoogle Scholar
  57. 57.
    Puceat M (2006) Stem cell therapy in heart failure: where do we stand and where are we heading? Heart Fail Monit 5:44–49PubMedGoogle Scholar
  58. 58.
    Miszta-Lane H, Mirbolooki M, James Shapiro AM et al (2006) Stem cell sources for clinical islet transplantation in type 1 diabetes: embryonic and adult stem cells. Med Hypotheses 67:909–913PubMedCrossRefGoogle Scholar
  59. 59.
    Schroeder IS, Kania G, Blyszczuk P et al (2006) Insulin-producing cells. Methods Enzymol 418:315–333PubMedCrossRefGoogle Scholar
  60. 60.
    Sanchez PL, San Roman JA, Villa A et al (2006) Contemplating the bright future of stem cell therapy for cardiovascular disease. Nat Clin Pract Cardiovasc Med 3 Suppl 1:S138–151PubMedCrossRefGoogle Scholar
  61. 61.
    Caplice NM (2006) The future of cell therapy for acute myocardial infarction. Nat Clin Pract Cardiovasc Med 3 Suppl 1:S129–132PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Mohan C. Vemuri
    • 1
  • Chellu S. Chetty
    • 2
  1. 1.Invitrogen CorporationNY
  2. 2.Department of Natural Sciences and MathematicsSavannah State UniversityGA

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