Tissue-Specific Stem Cells

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Cotransplantation of Placental Mesenchymal Stromal Cells Enhances Single and Double Cord Blood Engraftment in Nonobese Diabetic/Severe Combined Immune Deficient Mice†‡

  1. Smita D Hiwase1,2,
  2. Pamela G Dyson1,
  3. L. Bik To1,2,
  4. Ian D. Lewis1,2,§,¶,*

Article first published online: 19 JUN 2009

DOI: 10.1002/stem.157

Issue

STEM CELLS

STEM CELLS

Volume 27, Issue 9, pages 2293–2300, September 2009

Additional Information

How to Cite

Hiwase, S. D., Dyson, P. G., To, L. B. and Lewis, I. D. (2009), Cotransplantation of Placental Mesenchymal Stromal Cells Enhances Single and Double Cord Blood Engraftment in Nonobese Diabetic/Severe Combined Immune Deficient Mice. STEM CELLS, 27: 2293–2300. doi: 10.1002/stem.157

Author Information

  1. 1

    Department of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia

  2. 2

    Faculty of Health Sciences, Department of Medicine, University of Adelaide, Adelaide, Australia

  1. §

    Telephone: +61 #8 8222 3022; Fax: +61 #8 8222 3162

  2. website: http://www.sapthology.sa.gov.au

*Department of Hematology; IMVS; Frome Road; Adelaide, South Australia 5000

  1. †

    Author contributions: S.H.: Conception and design, performance of experiments, collection of data, data analysis and interpretation and manuscript writing; P.D.: Provision of study materials and proof reading the manuscript; L.B.T.: Data interpretation, manuscript writhing, final approval of manuscript and financial support; I.D.L.: Conception and design, financial support, administrative support, data interpretation, manuscript writing, final approval of manuscript and assistance with experiments.

  2. ‡

    First published online in STEM CELLS EXPRESS June 19, 2009.

Publication History

  1. Issue published online: 8 SEP 2009
  2. Article first published online: 19 JUN 2009
  3. Accepted manuscript online: 19 JUN 2009 12:00AM EST
  4. Manuscript Accepted: 11 JUN 2009
  5. Manuscript Received: 30 DEC 2008

Funded by

  • Dawes scholarship provided by the Royal Adelaide Research Committee, South Australia

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Keywords:

  • Placental mesenchymal stromal cells;
  • Cord blood transplantation;
  • Double cord blood transplant;
  • Chimerism;
  • Engraftment

Abstract

Limited cell numbers in a unit restricts cord blood transplantation (CBT) in adults. We evaluated whether cotransplantation of placental mesenchymal stromal cells (MSCs) would enhance engraftment. Plastic adherent cells from placenta demonstrated typical characteristics of MSCs. In six individual experiments, 4 cohorts of 24 nonobese diabetic/severe combined immune deficient (NOD/SCID) mice were evaluated. Cohort 1 received 5 × 104 CD34+ cells from unit (U) one (SCBT); cohort 2 received 5 × 104 CD34+ cells from U1 + 4 × 104 MSCs (SCBT+MSCs); cohort 3 received 2.5 × 104 CD34+ cells from U1 + 2.5 × 104 CD34+ cells from U2 (double cord blood transplant [DCBT]); cohort 4 received 2.5 × 104 CD34+ cells from U1 + 2.5 × 104 CD34+ cells from U2 + 4 × 104 MSCs (DCBT+MSCs). Hematopoietic engraftment evaluated after 6 to 8 weeks, was similar in recipients of SCBT and DCBT. MSC cotransplantation demonstrated enhanced engraftment in DCBT (51.8 ± 6.8% versus 14.9 ± 6.5%; p = .04) with an increased trend in SCBT (48.7 ± 7.7% versus 17.5 ± 6.1%; p = .07). In DCBT, cotransplantation of placental MSCs reduced single cord dominance. Self-renewal capacity was assessed by serial transplantation in secondary recipients infused with engrafted human cells from primary mice transplanted with or without MSCs. In secondary transplant experiments, 13 of 17 evaluable mice engrafted at levels of 1% to 6.5%. Despite enhanced engraftment in primary mice, long-term engraftment capacity was unaltered with MSC cotransplantation. Imaging studies showed MSCs migrated to pelvic region and improved cord blood (CB) CD34+ homing. Cotransplantation of placental MSCs enhanced cord blood engraftment and may act by improving homing of CD34+ cells. STEM CELLS 2009;27:2293–2300

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