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

• Published in: Blood 2002-03, Vol.99 (5), p.1585-1593
• Main Authors: Jetmore, Anna, Plett, P. Artur, Tong, Xia, Wolber, Frances M., Breese, Robert, Abonour, Rafat, Orschell-Traycoff, Christie M., Srour, Edward F.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antigens, CD34; Biological and medical sciences; Bone Marrow Cells - cytology; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Cycle - physiology; Cell differentiation, maturation, development, hematopoiesis; Cell Movement; Cell physiology; Fundamental and applied biological sciences. Psychology; Graft Survival - physiology; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Humans; Interphase - physiology; Medical sciences; Mice; Mice, Inbred NOD; Mice, SCID; Molecular and cellular biology; Spleen - cytology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation Conditioning; Transplantation, Heterologous
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V99.5.1585

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 nonobese diabetic severe combined immunodeficient (NOD/SCID) recipients. At 40 hours after transplantation (AT), only 1% of CD34+ cells, or their G0(G0CD34+) or G1(G1CD34+) 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/G2+M than in recipients of G0/G1 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.