Skip to main content
SpringerLink
Log in

Thriving for the Renewal of Life: Present Needs in Cell Therapy Translational Research

  • Chapter
  • First Online:
Regenerative Medicine: Laboratory to Clinic

  • 987 Accesses

Abstract

The stem cell field has grown very rapidly over the past decade and continues to be one of the most exciting areas of biomedical research. It is now known that stem cells are potential for improvement of pathological condition in many diseased organs, which is not possible in case of pharmaceutical drugs. Adult stem cells are most familiar for autologous and allogenic applications in different clinical indications. With the ability to produce an unlimited number of many kinds of human cells, the pluripotent stem cells have entered in the forefront of the regenerative medicine. However, several challenges must be overcome before clinical applications become a reality. More specifically, the challenges for the coming years are to extend multidisciplinary and multi-sector collaboration aimed at large-scale production of high-quality stem cell products, development of robust methods for characterization of cells, and assessment of therapeutic value. In this report, I have discussed about certain biological issues that might involve in determining the therapeutic potential and obtaining regulatory approval for the stem cell-based products. Other major aspect of this report has been manufacturing of cells and challenges for large-scale production.

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

Access this chapter

Log in via an institution

Institutional subscriptions

Abbreviations

ALF:

Acute liver failure

CHD:

Chronic heart disease

CLI:

Chronic liver injury

CPCs:

Cardiovascular progenitor cells

ESCs:

Embryonic stem cells

HSPCs:

Hematopoietic stem and progenitor cells

iPSCs:

Induced pluripotent stem cells

LVEF:

Left ventricular ejection fraction

MI:

Myocardial infarction

MSCs:

Mesenchymal stem cells

RPE:

Retinal pigment epithelium

SCI:

Spinal cord injury

References

  1. Mason C, Dunnill P. A brief definition of regenerative medicine. Regen Med. 2008;3:1–5.

    Article  PubMed  Google Scholar 

  2. Tavassoli M, Crosby WH. Transplantation of marrow to extramedullary sites. Science. 1968;161:54–6.

    Article  CAS  PubMed  Google Scholar 

  3. Clinical Trials Website of the United States Sponsored by the National Institutes of Health. http://clinicaltrials.gov.

  4. Chapel A, Bertho JM, Bensidhoum M, et al. Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome. J Gene Med. 2003;5:1028–38.

    Article  PubMed  Google Scholar 

  5. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105:1815–22.

    Article  CAS  PubMed  Google Scholar 

  6. Hsieh JY, Wang HW, Chang SJ, et al. Mesenchymal stem cells from human umbilical cord express preferentially secreted factors related to neuroprotection, neurogenesis, and angiogenesis. PLoS One. 2013;8:1–11.

    Google Scholar 

  7. Linero I, Chaparro O. Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS One. 2014;9:1–12.

    Article  Google Scholar 

  8. Ren G, Zhang L, Zhao X, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008;2:141–50.

    Article  CAS  PubMed  Google Scholar 

  9. Li N, Lu X, Zhao X, et al. Endothelial nitric oxide synthase promotes bone marrow stromal cell migration to the ischemic myocardium via upregulation of stromal cell-derived factor-1 alpha. Stem Cells. 2009;27:961–70.

    Article  CAS  PubMed  Google Scholar 

  10. Reffelmann T, Konemann S, Kloner RA. Promise of blood- and bone marrow-derived stem cell transplantation for functional cardiac repair: putting it in perspective with existing therapy. J Am Coll Cardiol. 2009;53:305–8.

    Article  PubMed  Google Scholar 

  11. Abdel-Latif A, Bolli R, Tleyjeh IM, et al. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007;167:989–97.

    Article  PubMed  Google Scholar 

  12. Jeevanantham V, Butler M, Saad A, et al. Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis. Circulation. 2012;126:551–68.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Martin G, Sutton J, Sharpe N. Left ventricular remodeling after myocardial infarction pathophysiology and therapy. Circulation. 2000;101:2981–8.

    Article  Google Scholar 

  14. Frank T, Henning WZ. Macrophage heterogeneity in liver injury and fibrosis. J Hepatol. 2014;60:1090–6.

    Google Scholar 

  15. El-Ansary M, Mogawer S, Abdel-Aziz I, et al. Phase I trial: mesenchymal stem cells transplantation in end stage liver disease. J Am Sci. 2010;6:135–44.

    Google Scholar 

  16. Zhang Z, Lin H, Shi M, et al. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol. 2012;27:112–20.

    Article  CAS  PubMed  Google Scholar 

  17. Akihiro S, Yoshio S, Takuya K, et al. Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model. Hepatology. 2013;58:1133–42.

    Google Scholar 

  18. Chiung-Kuei H, Soo OL, Kuo-Pao L, et al. Targeting androgen receptor in bone marrow mesenchymal stem cells leads to better transplantation therapy efficacy in liver cirrhosis. Hepatology. 2013;57:1550–63.

    Article  Google Scholar 

  19. di Bonzo LV, Ferrero I, Cravanzola C, et al. Human MSCs as a two-edge sword in hepatic regenerative medicine: engraftment and hepatic differentiation versus profibrogenic potential. Gut. 2008;57:223–31.

    Article  PubMed  Google Scholar 

  20. Forbes SJ, Russo FP, Rey V, et al. A significant proportion of myofibroblasts are of bone marrow origin in human liver fibrosis. Gastroenterology. 2004;126:955–63.

    Article  PubMed  Google Scholar 

  21. Russo FP, Alison MR, Bigger BW, et al. The bone marrow functionally contributes to liver fibrosis. Gastroenterology. 2006;130:1807–21.

    Article  PubMed  Google Scholar 

  22. Baligar P, Mukherjee S, Kochaat V, et al. Molecular and cellular functions distinguish superior therapeutic efficiency of bone marrow CD45 cells over mesenchymal stem cells in liver cirrhosis. Stem Cells. 2016;34:135–47.

    Article  CAS  PubMed  Google Scholar 

  23. Jin ZB, Okamoto S, Mandai M, et al. Induced pluripotent stem cells for retinal degenerative diseases: a new perspective on the challenges. J Genet. 2009;88:417–24.

    Article  PubMed  Google Scholar 

  24. Carr AJ, Smart MJ, Ramsden CM, et al. Development of human embryonic stem cell therapies for age-related macular degeneration. Trends Neurosci. 2013;36:385–95.

    Article  CAS  PubMed  Google Scholar 

  25. Mummery CL, Zhang J, Ng ES, et al. Differentiation of human embryonic stem cells and induced pluripotent stem cells to cardiomyocytes. Circ Res. 2012;111:344–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lian X, Bao X, Al-Ahmad A, et al. Efficient differentiation of human pluripotent stem cells to endothelial progenitors via small-molecule activation of WNT signaling. Stem Cell Rep. 2014;3:804–16.

    Article  CAS  Google Scholar 

  27. Imamura T. Differentiation of hepatocytes from mouse embryonic stem cells in three-dimensional culture system imitating in vivo environment. In:Embryonic stem cells – recent advances in pluripotent stem cell-based regenerative medicine: InTech; 2011. p. 291–300. doi:10.5772/14990.

  28. Wernig M, Benninger F, Schmandt T, et al. Functional integration of embryonic stem cell-derived neurons in vivo. J Neurosci. 2004;24:5258–68.

    Article  CAS  PubMed  Google Scholar 

  29. Nsair A, Schenke-Layland K, Handel BV, et al. Characterization and therapeutic potential of induced pluripotent stem cell-derived cardiovascular progenitor cells. PLoS One. 2012;7:e45603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Song H, Yoon C, Kattman SJ, et al. Interrogating functional integration between injected pluripotent stem cell-derived cells and surrogate cardiac tissue. Proc Natl Acad Sci U S A. 2010;107:3329–34.

    Article  CAS  PubMed  Google Scholar 

  31. Naumova AV, Modo M, Moore A, et al. Clinical imaging in regenerative medicine. Nat Biotechnol. 2014;32:804–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chugh AR, Beache GM, Loughran JH, et al. Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance. Circulation. 2012;126:S54–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Eich T, Eriksson O, Lundgren T. Visualization of early engraftment in clinical islet transplantation by positron-emission tomography. N Engl J Med. 2007;356:2754–5.

    Article  CAS  PubMed  Google Scholar 

  34. Guidance for Industry: Preclinical assessment of investigational cellular and gene therapy products. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/ucm376136.htm.

  35. Guidance for Industry: Potency tests for cellular and gene therapy products. http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM243392.pdf.

  36. Thomas RJ, Williams DJ. Large-scale manufacture of therapeutic human stem cells. Pharm Technol. 2009;33:74–9.

    Google Scholar 

  37. Wang H, Sun Z, Wang Y, et al. miR-33-5p, a novel mechano-sensitive microRNA promotes osteoblast differentiation by targeting Hmga2. Sci Rep. 2016;6:23170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Terraciano V, Hwang N, Moroni L, et al. Differential response of adult and embryonic mesenchymal progenitor cells to mechanical compression in hydrogels. Stem Cells. 2007;25:1730–2738.

    Article  Google Scholar 

  39. Kim DH, Heo SJ, Kang YG, et al. Shear stress and circumferential stretch by pulsatile flow direct vascular endothelial lineage commitment of mesenchymal stem cells in engineered blood vessels. J Mater Sci Mater Med. 2016;27:60.

    Article  PubMed  Google Scholar 

  40. Kirouac DC, Zandstra PW. The systematic production of cells for cell therapies. Cell Stem Cell. 2008;3:369–81.

    Article  CAS  PubMed  Google Scholar 

  41. Madlambayan GJ, Rogers I, Purpura KA, et al. Clinically relevant expansion of hematopoietic stem cells with conserved function in a single-use, closed-system bioprocess. Biol Blood Marrow Transplant. 2006;12:1020–30.

    Article  PubMed  Google Scholar 

  42. Boiron JM, Dazey B, Cailliot C, et al. Large-scale expansion and transplantation of CD34(+) hematopoietic cells: in vitro and in vivo confirmation of neutropenia abrogation related to the expansion process without impairment of the long-term engraftment capacity. Transfusion. 2006;46:1934–42.

    Article  PubMed  Google Scholar 

  43. Olmer R, Haase A, Merkert S, et al. Long term expansion of undifferentiated human iPS and ES cells in suspension culture using a defined medium. Stem Cell Res. 2010;5:51–64.

    Article  CAS  PubMed  Google Scholar 

  44. Storm MP, Orchard CB, Bone HK, et al. Three-dimensional culture systems for the expansion of pluripotent embryonic stem cells. Biotechnol Bioeng. 2010;107:683–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Want AJ, Nienow AW, Hewitt CJ, et al. Large-scale expansion and exploitation of pluripotent stem cells for regenerative medicine purposes: beyond the T flask. Regen Med. 2012;7:71–84.

    Article  CAS  PubMed  Google Scholar 

  46. Nienowa AW, Rafiqa QA, Coopmana K, et al. A potentially scalable method for the harvesting of hMSCs from microcarriers. Biochem Eng J. 2014;85:79–88.

    Article  Google Scholar 

  47. Zhao F, Ma T. Perfusion bioreactor system for human mesenchymal stem cell tissue engineering: dynamic cell seeding and construct development. Biotechnol Bioeng. 2005;91:482–93.

    Article  CAS  PubMed  Google Scholar 

  48. Lu B, Malcuit C, Wang S, et al. Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Stem Cells. 2009;27:2126–35.

    Article  CAS  PubMed  Google Scholar 

  49. Heathman TRJ, Nienow AW, McCall MJ, et al. The translation of cell-based therapies: clinical landscape and manufacturing challenges. Regen Med. 2015;10:49–64.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Stem Cell Biology, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India

    Asok Mukhopadhyay M.Tech., Ph.D.

Authors
  1. Asok Mukhopadhyay M.Tech., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Asok Mukhopadhyay M.Tech., Ph.D. .

Editor information

Editors and Affiliations

  1. Stem Cell Biology Laboratory, National Institute of Immunology, New Delhi, India

    Asok Mukhopadhyay

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Mukhopadhyay, A. (2017). Thriving for the Renewal of Life: Present Needs in Cell Therapy Translational Research. In: Mukhopadhyay, A. (eds) Regenerative Medicine: Laboratory to Clinic. Springer, Singapore. https://doi.org/10.1007/978-981-10-3701-6_20

Download citation

Publish with us

Policies and ethics

Search

Navigation