Homing efficiency, cell cycle kinetics, and survival of quiescent and cycling human CD34 + cells transplanted into conditioned NOD/SCID recipients

Anna Jetmore, P. Artur Plett, Xia Tong, Frances M. Wolber, Robert Breese, Rafat Abonour, Christie Orschell, Edward Srour

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Differences in engraftment potential of hematopoietic stem cells (HSCs) in distinct phases of cell cycle may result from the inability of cycling cells to home to the bone marrow (BM) and may be influenced by the rate of entry of BM-homed HSCs into cell cycle. Alternatively, preferential apoptosis of cycling cells may contribute to their low engraftment potential. This study examined homing, cell cycle progression, and survival of human hematopoietic cells transplanted into non-obese diabetic severe combined immunodeficient (NOD/SCID) recipients. At 40 hours after transplantation (AT), only 1% of CD34 + cells, or their G 0 (G 0CD34 +) or G 1 (G 1CD34 +) subfractions, was detected in the BM of recipient mice, suggesting that homing of engrafting cells to the BM was not specific. BM of NOD/SCID mice receiving grafts containing approximately 50% CD34 + cells harbored similar numbers of CD34 + and CD34 - cells, indicating that CD34 + cells did not preferentially traffic to the BM. Although more than 64% of human hematopoietic cells cycled in culture at 40 hours, more than 92% of cells recovered from NOD/SCID marrow were quiescent. Interestingly, more apoptotic human cells were detected at 40 hours AT in the BM of mice that received xenografts of expanded cells in S/G 2+M than in recipients of G 0/G 1 cells (34.6% ± 5.9% and 17.1% ± 6.3%, respectively; P < .01). These results suggest that active proliferation inhibition in the BM of irradiated recipients maintains mitotic quiescence of transplanted HSCs early AT and may trigger apoptosis of cycling cells. These data also illustrate that trafficking of transplanted cells to the BM is not selective, but lodgment of BM-homed cells may be specific.

Original languageEnglish
Pages (from-to)1585-1593
Number of pages9
JournalBlood
Volume99
Issue number5
DOIs
StatePublished - Mar 1 2002

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Cell Survival
Cell Cycle
Bone
Cells
Kinetics
Bone Marrow
Stem cells
Hematopoietic Stem Cells
Bone Marrow Cells
Apoptosis
Transplantation
Gastrin-Secreting Cells
Inbred NOD Mouse
SCID Mice
Heterografts
Grafts
Bone Marrow Transplantation
Transplants

ASJC Scopus subject areas

  • Hematology

Cite this

Homing efficiency, cell cycle kinetics, and survival of quiescent and cycling human CD34 + cells transplanted into conditioned NOD/SCID recipients. / Jetmore, Anna; Artur Plett, P.; Tong, Xia; Wolber, Frances M.; Breese, Robert; Abonour, Rafat; Orschell, Christie; Srour, Edward.

In: Blood, Vol. 99, No. 5, 01.03.2002, p. 1585-1593.

Research output: Contribution to journalArticle

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abstract = "Differences in engraftment potential of hematopoietic stem cells (HSCs) in distinct phases of cell cycle may result from the inability of cycling cells to home to the bone marrow (BM) and may be influenced by the rate of entry of BM-homed HSCs into cell cycle. Alternatively, preferential apoptosis of cycling cells may contribute to their low engraftment potential. This study examined homing, cell cycle progression, and survival of human hematopoietic cells transplanted into non-obese diabetic severe combined immunodeficient (NOD/SCID) recipients. At 40 hours after transplantation (AT), only 1{\%} of CD34 + cells, or their G 0 (G 0CD34 +) or G 1 (G 1CD34 +) subfractions, was detected in the BM of recipient mice, suggesting that homing of engrafting cells to the BM was not specific. BM of NOD/SCID mice receiving grafts containing approximately 50{\%} CD34 + cells harbored similar numbers of CD34 + and CD34 - cells, indicating that CD34 + cells did not preferentially traffic to the BM. Although more than 64{\%} of human hematopoietic cells cycled in culture at 40 hours, more than 92{\%} of cells recovered from NOD/SCID marrow were quiescent. Interestingly, more apoptotic human cells were detected at 40 hours AT in the BM of mice that received xenografts of expanded cells in S/G 2+M than in recipients of G 0/G 1 cells (34.6{\%} ± 5.9{\%} and 17.1{\%} ± 6.3{\%}, respectively; P < .01). These results suggest that active proliferation inhibition in the BM of irradiated recipients maintains mitotic quiescence of transplanted HSCs early AT and may trigger apoptosis of cycling cells. These data also illustrate that trafficking of transplanted cells to the BM is not selective, but lodgment of BM-homed cells may be specific.",
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