ACLS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pipes, B. L.
Right arrow Articles by Ablin, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pipes, B. L.
Right arrow Articles by Ablin, R. J.
Annals of Clinical & Laboratory Science 36:105-106 (2006)
© 2006 Association of Clinical Scientists

Letter to the Editor

Embryonic Stem Cell Co-Transplantation Revisited: Utility of Umbilical Cord Blood "Embryonic-Like" Stem Cells

Brian L. Pipes1 and Richard J. Ablin1,2,3
1 Department of Microbiology and Immunology, College of Medicine; 2 Arizona Cancer Center; and 3 Center for Injury Mechanisms and Related Responses, College of Nursing, University of Arizona, Tucson, Arizona

Address correspondence to Richard J. Ablin, Ph.D., Dept. of Microbiology and Immunology, College of Medicine, University of Arizona, 1501 North Campbell Ave., Tucson, AZ 85724-5049, USA; tel 520 626 7755; fax 520 626 2100; e-mail ablinri{at}email.arizona.edu.

To the Editor:

We read with considerable interest the recent Editorial on "Potential Benefits of Co-transplanting..." by Heng et a1 [1]. We have long been interested in the interactions between the local tissue micro-environment and wound healing and the influences of these interactions in related processes such as tumor development [2]. We are currently studying techniques of enhancing wound repair using exo-genous stem cell transplantation. The concept presented by Heng et a1 [1] of co-transplanting embryonic stem cells (ESC) along with exogenous adult tissue stem cells in order to modulate the damaged tissues’ inflammatory microenvironment while simultaneously providing increased numbers of viable tissue stem/progenitor cells for repair is attractive, and we believe it merits investigation. However, within this framework, we propose an alternative experimental implementation that may be logistically simpler and inherently safer.

The risk of teratoma formation mentioned in the original proposal of ESC co-transplantation is unfortunately not the only risk that must be weighed in deciding on using ESC. A flurry of developments in the study of ESC has recently revealed the disturbing fact that many ESC lines, while able to grow indefinitely in cell culture, have been accumulating an unexpectedly large amount of genetic damage [3]. Presumably directly related to their ability to grow for extensive periods in the genotoxic cell culture environment [4], this genetic damage could be expected to increase the rate of non-teratoma tumor development from these cells.

While the use of allogeneic ESC co-transplants, as mentioned in the original concept, might be expected to provoke an immune response capable of eventually eliminating all of the co-transplanted ESC (whether teratogenic or mutated), we feel that there is an alternate type of "stem-cell" that may provide the benefits of ESC while avoiding the drawbacks of accumulating ESC mutations, contaminated ESC stocks [5], and unresolved ethical concerns.

Umbilical cord blood (UCB) is a source of hematopoetic stem cells that is increasingly used for transplantation [6]. Work to clarify the relative amounts and phenotypes of these stem cells has revealed that UCB contains not only hematopoetic stem cells, but also non-hematopoetic stem cells: mesenchymal stem cells [7], "side-population" stem cells [8], primitive "beginner/Berashis" stem cells [9], and extremely primitive "embryonic-like" stem cells [10]. These cord blood-derived, embryonic-like stem cells (CBEs), express many of the characteristic surface markers associated with ESC in culture (eg, TRA-1-60, TRA-1-81, SSEA-4, SSEA-3, and Oct-4), and are capable of differentiating into hepatic tissue in a 3-dimensional microbioreactor model. Tissue repair studies using UCB stem cell transplantion, which show increased repair but no local UCB stem cell trans differentiation, are also consistent with the idea that there are UCB stem cells capable of secreting factors that modulate the repair capacity of endogenous tissue stem cells [11]. If the CBEs are capable of secreting these factors, they would be a very attractive alternative to the use of ESC as co-transplanted cellular "catalysts," as proposed by Heng et al [1].

We have initiated studies of the feasibility of using UCB-derived stem cells in co-transplantation experiments along with bone-marrow derived stem cells in an attempt to improve epithelial wound repair. We hope to determine if the concept of co-transplanting adult and "embryonic-like" stem cells to enhance tissue repair, and in particular our implementation using UCB-derived "embryonic-like" stem cells, is valid.

References

  1. Heng BC, Liu H, Cao T. Potential benefits of co-transplanting autologous adult stem cells together with human embryonic stem cells or their differentiated derivatives. Ann Clin Lab Sci 2005;35:3–6.[Free Full Text]
  2. He X, Tsang TC, Pipes BL, Ablin RJ, Harris DT. A stem cell fusion model of carcinogenesis. J Exp Therap Oncol 2005;5:101–109.
  3. Maitra A, Arking DE, Shivapurkar N, Ikeda M, Stastny V, Kassauei K, Sui G, Cutler DJ, Liu Y, Brimble SN, Noaksson K, Hyllner J, Schulz TC, Zeng X, Freed WJ, Crook J, Abraham S, Colman A, Sartipy P, Matsui S, Carpenter M, Gazdar AF, Rao M, Chakravarti A. Genomic alterations in cultured human embryonic stem cells. Nat Genet 2005;37:1099–1103.[Medline]
  4. Ben-Porath I, Weinberg RA. When cells get stressed: an integrative view of cellular senescence. J Clin Invest 2004;113:8–13.[Medline]
  5. Martin MJ, Muotri A, Gage F, Varki A. Human embryonic stem cells express an immunogenic non-human sialic acid. Nat Med 2005;11:228–232.[Medline]
  6. Benito AI, Diaz MA, Gonzalez-Vicent M, Sevilla J, Madero L. Hematopoietic stem cell transplantation using umbilical cord blood progenitors: review of current clinical results. Bone Marrow Transplant 2004;33:675–690.[Medline]
  7. Tondreau T, Meuleman N, Delforge A, Dejeneffe M, Leroy R, Massy M, Mortier C, Bron D, Lagneaux L. Mesenchymal stem cells derived from CD133-positive cells in mobilized peripheral blood and cord blood: proliferation, Oct4 expression, and plasticity. Stem Cells 2005; 23:1105–1112.[Medline]
  8. Eaker SS, Hawley TS, Ramezani A, Hawley RG. Detection and enrichment of hematopoietic stem cells by side population phenotype. Methods Mol Biol 2004;263:161–180.[Medline]
  9. Ende N. The Berashis cell: a review–is it similar to the embryonic stem cell? J Med 2000;31:113–130.[Medline]
  10. McGuckin CP, Forraz N, Baradez MO, Navran S, Zhao J, Urban R, Tilton R, Denner L. Production of stem cells with embryonic characteristics from human umbilical cord blood. Cell Prolif 2005;38:245–255.[Medline]
  11. Balsam LB, Robbins RC. Haematopoietic stem cells and repair of the ischaemic heart. Clin Sci 2005;109:483–492.[Medline]




This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pipes, B. L.
Right arrow Articles by Ablin, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pipes, B. L.
Right arrow Articles by Ablin, R. J.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS