We previously reported that bone marrow-derived CD8+/TCR– graft facilitating cells (FC) significantly enhance engraftment of HSC and prevent GVHD in mouse recipients. We have presently characterized a similar human CD8+/TCR– FC that comprised 1.48%±0.32% of total G-CSF-mobilized peripheral blood mononuclear cells. Approximately 55% of FC express CD56dim/- and the remaining express CD56bright. CD56dim/- FC contain CD3+ cells and CD19+ cells that highly express CXCR4. CD56bright FC contain CD11c+ and CD11b+ cells. To evaluate engraftment potential of human CD56dim/- or CD56bright FC subpopulations of human HSC, we transplanted 100,000 HSC alone or plus 300,000 CD56dim/- or CD56bright FC into NOD/SCID/IL2rΓnull (NSG) mice conditioned with 325 cGy of TBI. Only 34% of recipients of HSC alone engrafted compared to 65% of HSC plus CD56bright FC and 78% of HSC plus CD56dim/- FC. Donor chimerism in PB at one month was 1.1%±0.8%, 1.6%±0.4%, and 4.1%±1.3% respectively. Donor chimerism of HSC alone recipients at 6 months was 3.8%±3.5% in PB, 2.9%±1.3% in BM and 12.3%±9.8% in spleen. In contrast, HSC plus CD56bright FC or CD56dim/- FC exhibited durable donor chimerism and showed higher level of donor chimerism in PB (8.8%±6.4% or 9.1%±6.0%), in BM (14.5%±7.2% or 11.6%±4.8%), and in spleen (8.2%±3.3% or 26.3%±11.3%). To evaluate if FC enhance homing of HSC to BM, HSC plus CD56bright or CD56dim/- FC were transplanted into NSG mice supralethally conditioned with 1100 cGy of TBI. BM cells were harvested from recipients at 16 hours after transplantation and placed in colony forming cell (CFC) assay. Recipients of HSC plus CD56dim/- FC generated significantly more colonies compared with HSC plus CD56bright FC or HSC alone (P<0.05), indicating that CD56dim/- FC enhance homing of donor HSC and progenitors to the BM. To test if CD56dim/- FC promote HSC differentiation, HSC were incubated with CD56dim/- FC for 18hrs and cultured for 14 days in CFC assay. HSC plus CD56dim/- FC generated significantly more colonies compared with HSC alone (P=0.038), suggesting that human CD56dim/- FC have a direct effect on clonogenicity of HSC. Our data indicate that: 1) human CD8+/TCR– FC are heterogeneous; 2) CD56dim/- FC enhance homing of HSC to BM and promote HSC clonogenicity; and 3) both CD56dim/- and CD56bright FC maintain a durable and high level of donor chimerism in PB, BM, spleen.
Bozulic, L.: Employee, Regenerex. Ildstad, S.: Other, Regenerex, a Biotech Start-Up Company, Equity/Employee. Colvin-Adams, M.: Other, Regenerex, a Biotech Start-Up Company, Equity/Employee.
To cite this abstract in AMA style:Huang Y, Elliott M, Miller T, Bozulic L, Corbin D, Wen Y, Xu H, Ildstad S. Characterization of Human CD8+/TCR-/CD56dim/- Facilitating Cells In Vivo and In Vitro [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/characterization-of-human-cd8tcr-cd56dim-facilitating-cells-in-vivo-and-in-vitro/. Accessed July 24, 2021.
« Back to 2013 American Transplant Congress