Ex vivo expanded umbilical cord blood T cells maintain naive phenotype and TCR diversity

S. Parmar, S. N. Robinson, Krishna V Komanduri, L. St. John, W. Decker, D. Xing, H. Yang, J. McMannis, R. Champlin, M. de Lima, J. Molldrem, A. Rieber, M. Bonyhadi, R. Berenson, E. J. Shpall

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Umbilical cord blood (CB) is a promising source of hematopoietic stem cells for allogeneic transplantation. However, delayed engraftment and impaired immune reconstitution remain major limitations. Enrichment of donor grafts with CB T cells expanded ex vivo might facilitate improved T-cell immune reconstitution post-transplant. We hypothesized that CB T cells could be expanded using paramagnetic microbeads covalently linked to anti-CD3 and anti-CD28 Ab. Methods: CB units were divided into three fractions: (1) cells cultured without beads, (2) cells cultured with beads and (3) cells cultured with beads following CD3+ magnetic enrichment. All fractions were cultured for 14 days in the presence of IL-2 (200 IU/mL). Results: A mean 100-fold expansion (range 49-154) of total nucleated cells was observed in the CD3+ magnetically enriched fraction. Following expansion, CB T cells retained a naive and/or central memory phenotype and contained a polyclonal TCR diversity demonstrated by spectratyping. Discussion: Our data provide evidence that naive and diverse CB T cells may be expanded ex vivo and warrant additional studies in the setting of human CB transplantation.

Original languageEnglish
Pages (from-to)149-157
Number of pages9
JournalCytotherapy
Volume8
Issue number2
DOIs
StatePublished - May 1 2006
Externally publishedYes

Fingerprint

Fetal Blood
Blood Cells
T-Lymphocytes
Phenotype
Cultured Cells
Transplants
Hematopoietic Stem Cell Transplantation
Homologous Transplantation
Microspheres
Interleukin-2
Transplantation

Keywords

  • Cord blood transplant
  • Naive T cells
  • T-cell expansion

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

Parmar, S., Robinson, S. N., Komanduri, K. V., St. John, L., Decker, W., Xing, D., ... Shpall, E. J. (2006). Ex vivo expanded umbilical cord blood T cells maintain naive phenotype and TCR diversity. Cytotherapy, 8(2), 149-157. https://doi.org/10.1080/14653240600620812

Ex vivo expanded umbilical cord blood T cells maintain naive phenotype and TCR diversity. / Parmar, S.; Robinson, S. N.; Komanduri, Krishna V; St. John, L.; Decker, W.; Xing, D.; Yang, H.; McMannis, J.; Champlin, R.; de Lima, M.; Molldrem, J.; Rieber, A.; Bonyhadi, M.; Berenson, R.; Shpall, E. J.

In: Cytotherapy, Vol. 8, No. 2, 01.05.2006, p. 149-157.

Research output: Contribution to journalArticle

Parmar, S, Robinson, SN, Komanduri, KV, St. John, L, Decker, W, Xing, D, Yang, H, McMannis, J, Champlin, R, de Lima, M, Molldrem, J, Rieber, A, Bonyhadi, M, Berenson, R & Shpall, EJ 2006, 'Ex vivo expanded umbilical cord blood T cells maintain naive phenotype and TCR diversity', Cytotherapy, vol. 8, no. 2, pp. 149-157. https://doi.org/10.1080/14653240600620812
Parmar, S. ; Robinson, S. N. ; Komanduri, Krishna V ; St. John, L. ; Decker, W. ; Xing, D. ; Yang, H. ; McMannis, J. ; Champlin, R. ; de Lima, M. ; Molldrem, J. ; Rieber, A. ; Bonyhadi, M. ; Berenson, R. ; Shpall, E. J. / Ex vivo expanded umbilical cord blood T cells maintain naive phenotype and TCR diversity. In: Cytotherapy. 2006 ; Vol. 8, No. 2. pp. 149-157.
@article{65a1a5689c8c4a6ebc99ee04a202d2f3,
title = "Ex vivo expanded umbilical cord blood T cells maintain naive phenotype and TCR diversity",
abstract = "Background: Umbilical cord blood (CB) is a promising source of hematopoietic stem cells for allogeneic transplantation. However, delayed engraftment and impaired immune reconstitution remain major limitations. Enrichment of donor grafts with CB T cells expanded ex vivo might facilitate improved T-cell immune reconstitution post-transplant. We hypothesized that CB T cells could be expanded using paramagnetic microbeads covalently linked to anti-CD3 and anti-CD28 Ab. Methods: CB units were divided into three fractions: (1) cells cultured without beads, (2) cells cultured with beads and (3) cells cultured with beads following CD3+ magnetic enrichment. All fractions were cultured for 14 days in the presence of IL-2 (200 IU/mL). Results: A mean 100-fold expansion (range 49-154) of total nucleated cells was observed in the CD3+ magnetically enriched fraction. Following expansion, CB T cells retained a naive and/or central memory phenotype and contained a polyclonal TCR diversity demonstrated by spectratyping. Discussion: Our data provide evidence that naive and diverse CB T cells may be expanded ex vivo and warrant additional studies in the setting of human CB transplantation.",
keywords = "Cord blood transplant, Naive T cells, T-cell expansion",
author = "S. Parmar and Robinson, {S. N.} and Komanduri, {Krishna V} and {St. John}, L. and W. Decker and D. Xing and H. Yang and J. McMannis and R. Champlin and {de Lima}, M. and J. Molldrem and A. Rieber and M. Bonyhadi and R. Berenson and Shpall, {E. J.}",
year = "2006",
month = "5",
day = "1",
doi = "10.1080/14653240600620812",
language = "English",
volume = "8",
pages = "149--157",
journal = "Cytotherapy",
issn = "1465-3249",
publisher = "Informa Healthcare",
number = "2",

}

TY - JOUR

T1 - Ex vivo expanded umbilical cord blood T cells maintain naive phenotype and TCR diversity

AU - Parmar, S.

AU - Robinson, S. N.

AU - Komanduri, Krishna V

AU - St. John, L.

AU - Decker, W.

AU - Xing, D.

AU - Yang, H.

AU - McMannis, J.

AU - Champlin, R.

AU - de Lima, M.

AU - Molldrem, J.

AU - Rieber, A.

AU - Bonyhadi, M.

AU - Berenson, R.

AU - Shpall, E. J.

PY - 2006/5/1

Y1 - 2006/5/1

N2 - Background: Umbilical cord blood (CB) is a promising source of hematopoietic stem cells for allogeneic transplantation. However, delayed engraftment and impaired immune reconstitution remain major limitations. Enrichment of donor grafts with CB T cells expanded ex vivo might facilitate improved T-cell immune reconstitution post-transplant. We hypothesized that CB T cells could be expanded using paramagnetic microbeads covalently linked to anti-CD3 and anti-CD28 Ab. Methods: CB units were divided into three fractions: (1) cells cultured without beads, (2) cells cultured with beads and (3) cells cultured with beads following CD3+ magnetic enrichment. All fractions were cultured for 14 days in the presence of IL-2 (200 IU/mL). Results: A mean 100-fold expansion (range 49-154) of total nucleated cells was observed in the CD3+ magnetically enriched fraction. Following expansion, CB T cells retained a naive and/or central memory phenotype and contained a polyclonal TCR diversity demonstrated by spectratyping. Discussion: Our data provide evidence that naive and diverse CB T cells may be expanded ex vivo and warrant additional studies in the setting of human CB transplantation.

AB - Background: Umbilical cord blood (CB) is a promising source of hematopoietic stem cells for allogeneic transplantation. However, delayed engraftment and impaired immune reconstitution remain major limitations. Enrichment of donor grafts with CB T cells expanded ex vivo might facilitate improved T-cell immune reconstitution post-transplant. We hypothesized that CB T cells could be expanded using paramagnetic microbeads covalently linked to anti-CD3 and anti-CD28 Ab. Methods: CB units were divided into three fractions: (1) cells cultured without beads, (2) cells cultured with beads and (3) cells cultured with beads following CD3+ magnetic enrichment. All fractions were cultured for 14 days in the presence of IL-2 (200 IU/mL). Results: A mean 100-fold expansion (range 49-154) of total nucleated cells was observed in the CD3+ magnetically enriched fraction. Following expansion, CB T cells retained a naive and/or central memory phenotype and contained a polyclonal TCR diversity demonstrated by spectratyping. Discussion: Our data provide evidence that naive and diverse CB T cells may be expanded ex vivo and warrant additional studies in the setting of human CB transplantation.

KW - Cord blood transplant

KW - Naive T cells

KW - T-cell expansion

UR - http://www.scopus.com/inward/record.url?scp=33646428948&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646428948&partnerID=8YFLogxK

U2 - 10.1080/14653240600620812

DO - 10.1080/14653240600620812

M3 - Article

C2 - 16698688

AN - SCOPUS:33646428948

VL - 8

SP - 149

EP - 157

JO - Cytotherapy

JF - Cytotherapy

SN - 1465-3249

IS - 2

ER -