Expansion of LTC-ICs and maintenance of p21 and BCL-2 expression in cord blood CD34+/CD38- early progenitors cultured over human MSCs as a feeder layer

Suzanne Kadereit, Linda S. Deeds, Stephen E. Haynesworth, Omer N. Koc, Margaret M. Kozik, Emese Szekely, Kathleen Daum-Woods, Glenn W. Goetchius, Pingfu Fu, Lisbeth A. Welniak, William J Murphy, Mary J. Laughlin

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Allogeneic transplantation with umbilical cord blood (UCB) is limited in adult recipients by a low CD34+ cell dose. Clinical trials incorporating cytokine-based UCB in vitro expansion have not demonstrated significant shortening of hematologic recovery despite substantial increases in CD34+ cell dose, suggesting loss of stem cell function. To sustain stem cell function during cytokine-based in vitro expansion, a feeder layer of human mesenchymal stem cells (MSCs) was incorporated in an attempt to mimic the stem cell niche in the marrow microenvironment. UCB expansion on MSCs resulted in a 7.7-fold increase in total LTC-IC output and a 3.8-fold increase of total early CD34+ progenitors (CD38-/HLA- DR-). Importantly, early CD34+/CD38-/HLA-DR- progenitors from cultures expanded on MSCs demonstrated higher cytoplasmic expression of the cell-cycle inhibitor, p21cip1/waf1, and the antiapoptotic protein, BCL-2, compared with UCB expanded in cytokines alone, suggesting improved maintenance of stem cell function in the presence of MSCs. Moreover, the presence of MSCs did not elicit UCB lymphocyte activation. Taken together, these results strongly suggest that the addition of MSCs as a feeder layer provides improved conditions for expansion of early UCB CD34+/CD38-/HLA-DR- hematopoietic progenitors and may serve to inhibit their differentiation and rates of apoptosis during short-term in vitro expansion.

Original languageEnglish (US)
Pages (from-to)573-582
Number of pages10
JournalStem Cells
Volume20
Issue number6
StatePublished - 2002
Externally publishedYes

Fingerprint

Feeder Cells
Mesenchymal Stromal Cells
Fetal Blood
Maintenance
HLA-DR Antigens
Stem Cells
Cytokines
Stem Cell Niche
Homologous Transplantation
Lymphocyte Activation
Cell Cycle
Bone Marrow
Clinical Trials
Apoptosis
In Vitro Techniques
Proteins

Keywords

  • Expansion
  • Hematopoietic progenitors
  • Mesenchymal stem cells
  • UCB

ASJC Scopus subject areas

  • Cell Biology

Cite this

Kadereit, S., Deeds, L. S., Haynesworth, S. E., Koc, O. N., Kozik, M. M., Szekely, E., ... Laughlin, M. J. (2002). Expansion of LTC-ICs and maintenance of p21 and BCL-2 expression in cord blood CD34+/CD38- early progenitors cultured over human MSCs as a feeder layer. Stem Cells, 20(6), 573-582.

Expansion of LTC-ICs and maintenance of p21 and BCL-2 expression in cord blood CD34+/CD38- early progenitors cultured over human MSCs as a feeder layer. / Kadereit, Suzanne; Deeds, Linda S.; Haynesworth, Stephen E.; Koc, Omer N.; Kozik, Margaret M.; Szekely, Emese; Daum-Woods, Kathleen; Goetchius, Glenn W.; Fu, Pingfu; Welniak, Lisbeth A.; Murphy, William J; Laughlin, Mary J.

In: Stem Cells, Vol. 20, No. 6, 2002, p. 573-582.

Research output: Contribution to journalArticle

Kadereit, S, Deeds, LS, Haynesworth, SE, Koc, ON, Kozik, MM, Szekely, E, Daum-Woods, K, Goetchius, GW, Fu, P, Welniak, LA, Murphy, WJ & Laughlin, MJ 2002, 'Expansion of LTC-ICs and maintenance of p21 and BCL-2 expression in cord blood CD34+/CD38- early progenitors cultured over human MSCs as a feeder layer', Stem Cells, vol. 20, no. 6, pp. 573-582.
Kadereit, Suzanne ; Deeds, Linda S. ; Haynesworth, Stephen E. ; Koc, Omer N. ; Kozik, Margaret M. ; Szekely, Emese ; Daum-Woods, Kathleen ; Goetchius, Glenn W. ; Fu, Pingfu ; Welniak, Lisbeth A. ; Murphy, William J ; Laughlin, Mary J. / Expansion of LTC-ICs and maintenance of p21 and BCL-2 expression in cord blood CD34+/CD38- early progenitors cultured over human MSCs as a feeder layer. In: Stem Cells. 2002 ; Vol. 20, No. 6. pp. 573-582.
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AU - Haynesworth, Stephen E.

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