Plett PA, Frankovitz S, Jetmore A, Abonour R, Orschell-Traycoff CM.

Exp Hematol. 2000 Jul; 28: 98.

Indiana University School of Medicine, Indianapolis, USA.

The ability of the rotating wall vessel (RWV) bioreactor, developed by NASA for benchtop simulation of microgravity, to support expansion of primitive human hematopoietic progenitor cells (HPC) was assessed during short-term cultures. Human bone marrow (BM) enriched for CD34+ cells (mean purity = 85%, n = 3) was seeded at 1.1 to 2.0 x 10e5 cells/mL in 10 mL in RWV, and incubated in the presence of SCF, IL-3, IL-6, GM-CSF, Flt-3L, and MGDF in either simulated microgravity or earth gravity (1-G). Proliferation of these cells after 5 days of culture averaged 11 +/- 10-fold in microgravity, compared to 4.1 +/- 3-fold in 1-G control cultures. Expansion of CD34+ cells was also greater in microgravity cultures compared to 1-G (2.6 +/- 2.6 vs. 1.0 +/- 0.8, respectively), as well as expansion of more primitive CD34+ CD38-/lo cells (1.9 +/- 1.4 vs. 0.8 +/- 0.6, respectively). To further examine the hematopoietic potential of CD34+ cells propagated in microgravity, long-term repopulating potential was assessed in NOD/SCID recipients. Conditioned NOD/SCID mice were transplanted with either fresh day 0 CD34-enriched BM cells (570K to 990K/mouse), or progeny of equivalent cell numbers expanded in microgravity (2.5 to 11.4 x 10e6/mouse) or 1-G (1.5 to 3.9 x 10e6/mouse). Fresh CD34+ cells provided 39 +/- 14% chimerism at 8 weeks of post-transplantation. Despite possessing in microgravity were deficient in NOD/SCID-repopulating potential compared to 1-G controls (2.1 +/- 1.4, n = 4 vs. 14.8 +/- 13, n = 4, respectively). To examine whether diminished homing may contribute to the reduced engraftment of microgravity cells, adhesion molecule expression was analyzed. While no differences were found between microgravity and 1-G CD34+ cells in their adhesion molecule repertoire, these cells expressed considerably different levels of CD11a, CD43, CD44, CD49d, CD49e, CD62L, and CXCR4 in comparison to day 0 CD34+ cells, possibly contributing to their reduced engraftment potential. These results in simulated microgravity shed further light on stem cell biology, and may begin to explain some of the hematologic changes occurring in humans exposed to true microgravity.

Publication Types:

• Meeting Abstracts

Keywords:

• ADP-ribosyl Cyclase
• Animals
• Antigens, CD
• Antigens, CD34
• Antigens, CD43
• Bone Marrow Cells
• Cell Adhesion Molecules
• Hematopoiesis
• Hematopoietic Stem Cells
• Humans
• Interleukin-3
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Receptors, CXCR4
• Weightlessness
• immunology

Other ID:

• 20604817

UI: 102195022

From Meeting Abstracts