Human umbilical cord blood hematopoietic progenitor cells: Are they the same as their adult bone marrow counterparts?

Christie Orschell, M. R. Abboud, J. Laver, D. Clapp, R. Hoffman, P. Law, Edward Srour

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

In an attempt to expand the hematopoietic progenitor cell (HPC) content of a single collection of umbllical cord blood (CB), we investigated the ex vivo proliferative potential of CB CD34+ cells and the rate of exit of these cells from G0/G1 phases of cell cycle in response to different cytokine combinations. Initial experiments in which phenotypically defined populations of CB and adult bone marrow (BM) CD34+ cells were examined for their HPC content revealed that, contrary to BM, CB CD34+ human leukocyte A (HLA)-DR+ cells appeared to contain the majority of primitive HPC. In cultures of BM CD34+ HLA-DR+ cells incubated with stem cell factor (SCF) + interleukin-3 (IL-3), CD34+ cells increased five-fold over 5 days, while CD34+ cells from CB CD34+ HLA-DR+ cultures increased II-fold under these same conditions, illustrating an enhanced proliferative potential of CB CD34+ HLA-DR+ cells vs. similar cells from adult BM. Furthermore, a 6.2-fold increase in the number of CB CD34+ still residing in G0/G1 was observed on day 5 in cultures supplemented with SCF and IL-3, suggesting the generation of large numbers of primitive HPC in vitro. The effect of SCF on the exit of CB and BM CD34+ HLA-DR+ cells from G0/G1 was then examined. Following 36- to 48-hour exposure to SCF, 45% of quiescent CB cells exited G0/G1 in contrast to only 13% of quiescent BM cells. In serum-free media supplemented with either SCF or IL-3 alone, CB CD34+ HLA-DR+ cells did not exit G0/G1 phases of cell cycle as rapidly as when CB plasma was present, unless SCF and IL-3 were added simultaneously. Collectively, these results suggest that CB CD34+ cells are more responsive to cytokine stimulation, especially SCF, and may represent more suitable candidates for ex vivo expansion of HPC than BM cells. Furthermore, these data illustrate potentially important biologic differences between the HPC content of subpopulations of BM and CB cells, and the response of these subpopulations to cytokine stimulation.

Original languageEnglish
Pages (from-to)382-391
Number of pages10
JournalBlood Cells
Volume20
Issue number2-3
StatePublished - 1994

Fingerprint

Hematopoietic Stem Cells
Fetal Blood
Bone Marrow
Stem Cell Factor
Leukocytes
Interleukin-3
Bone Marrow Cells
Blood Cells
Cell Cycle Resting Phase
G1 Phase
Cytokines
Cell Cycle
Serum-Free Culture Media

Keywords

  • cell culture
  • cell cycle
  • cord blood
  • progenitor cells

ASJC Scopus subject areas

  • Hematology

Cite this

Human umbilical cord blood hematopoietic progenitor cells : Are they the same as their adult bone marrow counterparts? / Orschell, Christie; Abboud, M. R.; Laver, J.; Clapp, D.; Hoffman, R.; Law, P.; Srour, Edward.

In: Blood Cells, Vol. 20, No. 2-3, 1994, p. 382-391.

Research output: Contribution to journalArticle

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title = "Human umbilical cord blood hematopoietic progenitor cells: Are they the same as their adult bone marrow counterparts?",
abstract = "In an attempt to expand the hematopoietic progenitor cell (HPC) content of a single collection of umbllical cord blood (CB), we investigated the ex vivo proliferative potential of CB CD34+ cells and the rate of exit of these cells from G0/G1 phases of cell cycle in response to different cytokine combinations. Initial experiments in which phenotypically defined populations of CB and adult bone marrow (BM) CD34+ cells were examined for their HPC content revealed that, contrary to BM, CB CD34+ human leukocyte A (HLA)-DR+ cells appeared to contain the majority of primitive HPC. In cultures of BM CD34+ HLA-DR+ cells incubated with stem cell factor (SCF) + interleukin-3 (IL-3), CD34+ cells increased five-fold over 5 days, while CD34+ cells from CB CD34+ HLA-DR+ cultures increased II-fold under these same conditions, illustrating an enhanced proliferative potential of CB CD34+ HLA-DR+ cells vs. similar cells from adult BM. Furthermore, a 6.2-fold increase in the number of CB CD34+ still residing in G0/G1 was observed on day 5 in cultures supplemented with SCF and IL-3, suggesting the generation of large numbers of primitive HPC in vitro. The effect of SCF on the exit of CB and BM CD34+ HLA-DR+ cells from G0/G1 was then examined. Following 36- to 48-hour exposure to SCF, 45{\%} of quiescent CB cells exited G0/G1 in contrast to only 13{\%} of quiescent BM cells. In serum-free media supplemented with either SCF or IL-3 alone, CB CD34+ HLA-DR+ cells did not exit G0/G1 phases of cell cycle as rapidly as when CB plasma was present, unless SCF and IL-3 were added simultaneously. Collectively, these results suggest that CB CD34+ cells are more responsive to cytokine stimulation, especially SCF, and may represent more suitable candidates for ex vivo expansion of HPC than BM cells. Furthermore, these data illustrate potentially important biologic differences between the HPC content of subpopulations of BM and CB cells, and the response of these subpopulations to cytokine stimulation.",
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T2 - Are they the same as their adult bone marrow counterparts?

AU - Orschell, Christie

AU - Abboud, M. R.

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AU - Clapp, D.

AU - Hoffman, R.

AU - Law, P.

AU - Srour, Edward

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N2 - In an attempt to expand the hematopoietic progenitor cell (HPC) content of a single collection of umbllical cord blood (CB), we investigated the ex vivo proliferative potential of CB CD34+ cells and the rate of exit of these cells from G0/G1 phases of cell cycle in response to different cytokine combinations. Initial experiments in which phenotypically defined populations of CB and adult bone marrow (BM) CD34+ cells were examined for their HPC content revealed that, contrary to BM, CB CD34+ human leukocyte A (HLA)-DR+ cells appeared to contain the majority of primitive HPC. In cultures of BM CD34+ HLA-DR+ cells incubated with stem cell factor (SCF) + interleukin-3 (IL-3), CD34+ cells increased five-fold over 5 days, while CD34+ cells from CB CD34+ HLA-DR+ cultures increased II-fold under these same conditions, illustrating an enhanced proliferative potential of CB CD34+ HLA-DR+ cells vs. similar cells from adult BM. Furthermore, a 6.2-fold increase in the number of CB CD34+ still residing in G0/G1 was observed on day 5 in cultures supplemented with SCF and IL-3, suggesting the generation of large numbers of primitive HPC in vitro. The effect of SCF on the exit of CB and BM CD34+ HLA-DR+ cells from G0/G1 was then examined. Following 36- to 48-hour exposure to SCF, 45% of quiescent CB cells exited G0/G1 in contrast to only 13% of quiescent BM cells. In serum-free media supplemented with either SCF or IL-3 alone, CB CD34+ HLA-DR+ cells did not exit G0/G1 phases of cell cycle as rapidly as when CB plasma was present, unless SCF and IL-3 were added simultaneously. Collectively, these results suggest that CB CD34+ cells are more responsive to cytokine stimulation, especially SCF, and may represent more suitable candidates for ex vivo expansion of HPC than BM cells. Furthermore, these data illustrate potentially important biologic differences between the HPC content of subpopulations of BM and CB cells, and the response of these subpopulations to cytokine stimulation.

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